Is hip fracture surgery safe for patients on antiplatelet drugs and is it necessary to delay surgery? A Systematic Review and Meta-analysis

Is hip fracture surgery safe for patients on antiplatelet drugs and is it necessary to delay surgery? 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A Systematic Review and Meta-analysis Zhanyu Yang, Jiangdong Ni, Ze Long, Letian Kuang, Yongquan Gao, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.23034/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Mar, 2020 Read the published version in Journal of Orthopaedic Surgery and Research → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Hip fractures are common and account for a large proportion of orthopaedic surgical admissions in elderly patients. However, determining the timing for surgery has been controversial for patients who develop with hip fractures while on antiplatelet treatment. Methods: Computerized databases for studies published from the inception date to January 2020, including the Cochrane Library, PubMed (Medline), EMBASE, Web of Science TM , ClinicalTrials, ClinicalKey and Google Scholar, were searched using the keywords “Hip AND Fracture”, “Antiplatelet”, “Antithrombocyte”, “Platelet aggregation inhibitors”, “Aspirin”, “Plavix”, and “Clopidogrel”. Results: In total, 2328 initial articles were identified. Twenty-four studies with 5423 participants were ultimately included in our analysis. Early surgery was associated with an increased transfusion rate in the antiplatelet group compared to the non-antiplatelet group (OR = 1.21; 95% CI, 1.01 to 1.44; p = 0.03). Early surgery for hip fracture patients on antiplatelet therapy was associated with a greater decrease in haemoglobin compared to delayed surgery (WMD = 0.75; 95% CI, 0.50 to 1.00; p < 0.001). However, early surgery appeared to decrease the length of hospitalization (WMD = -6.05; 95% CI, -7.06 to -5.04; p < 0.001) and mortality (OR = 0.43; 95% CI, 0.23 to 0.79; p = 0.006). Conclusion: It is unnecessary to delay surgery to restore platelet function when patients with hip fractures receive antiplatelet therapy. Furthermore, early surgery can significantly reduce mortality and hospital stay, which is conducive to patient recovery. Future randomized trials should determine whether the results are sustained over time. Orthopedics Orthopedic Surgery Hip fractures meta-analysis platelet aggregation inhibitors aspirin Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Background Hip fractures are among the main causes of orthopaedic surgical admissions and life-threatening injuries that occur worldwide, mainly in elderly individuals. Older patients are particularly vulnerable to sustaining hip fractures because of the high prevalence of osteoporosis or osteopenia. According to the American Academy of Orthopaedic Surgeons, each year, the number of hospital admissions due to hip fractures can reach up to 350,000.[1] By the year 2040, there will be more than 500,000 people with hip fractures per year, with an annual medical expenditure of at least $9.8 billion.[1,2] Although the development of surgical instruments and medical technology for early mobilization has advanced significantly, the mortality rate remains high. The cause of this high mortality rate is not entirely clear, and most of the deaths are ascribed to comorbidities, including cardiovascular disease.[3,4] Antiplatelet drugs are simultaneously used in most hip fracture patients for primary and secondary prevention of cardiovascular or cerebrovascular events. Because the inhibitory action of drugs on platelets is irreversible and mature platelets do not synthesize new proteins, antiplatelet drugs make platelets ineffective for approximately seven days, the mean lifetime of a platelet.[5] Despite the obvious advantages in the prevention and treatment of cardiovascular diseases, the continued use of antiplatelet drugs perioperatively may have great risks. Clopidogrel therapy in cardiac surgery without preoperative disruption increased haemorrhagic risks, transfusion demands and infection with a poor prognosis.[6] The potential haematoma risk in orthopaedic surgery[7] forces withdrawal of antiplatelet drugs and delays surgery for at least 5 days to allow platelet function to return to an adequate status. Currently, no agreed upon guidelines exist for the appropriate surgical time for patients suffering hip fractures while on antiplatelet therapy, and there is a marked divergence of opinion on the final results of early and delayed surgical intervention.[8] Therefore, the purpose of this review was to identify whether early surgical intervention can be safely implemented on patients who develop hip fractures while on antiplatelet therapy to promote satisfactory outcomes. A secondary aim was to determine whether early or delayed surgery was more appropriate for those patients. Moreover, we attempt to establish a framework for managing hip fracture patients with antiplatelet therapy. Methods Literature Search This review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis statement (PRISMA).[ 9 ] The following databases were fully searched from their inception date to January 2020: PubMed, EMBASE, the Cochrane Library, Web of Science™, ClinicalTrials, ClinicalKey and Google Scholar. For each database, a specific search strategy was developed using the following keywords: “Hip AND Fracture”, “Antiplatelet”, “Antithrombocyte”, “Platelet aggregation inhibitors”, “Aspirin”, “Plavix”, and “Clopidogrel” (detailed search strategies as shown in Additional files 1). Searches were without date or geographic restriction but were limited to primary studies written in English. All references of retrieved articles were also checked for additional relevant studies. Inclusion and Exclusion Criteria Studies were included according to the following inclusion criteria: (1) randomized-controlled trials or high-quality observational studies; (2) studies that compared the use of antiplatelet drugs on admission with placebo or no treatment in hip fracture patients undergoing early surgery (the time from admission to theatre < 5 days); and (3) studies that compared early surgery ( 5 days) for patients suffering hip fractures while on antiplatelet therapy. Based on previous studies and half-life of antiplatelet drugs, we set 5 days as the dividing line. The exclusion criteria were as follows: (1) studies comparing non-antiplatelet medication, such as warfarin or low molecular weight heparin; (2) non-clinical studies such as basic science studies, narrative reviews, surveys, letters, editorials, case series, case reports, comments, conference abstracts or expert opinions; and (3) non-English studies. The potential overlap of subjects was evaluated by comparing demographic characteristics when multiple studies were conducted by the same author or research institute. Titles and abstracts were filtered and evaluated independently in a non-blinded standardized pattern. A final decision was made based on the adherence to the inclusion and exclusion criteria. Divergence was resolved by consensus. As shown in Fig. 1 , from the search, 2328 potentially eligible records were identified (including duplicates), 137 studies from The Cochrane Library, 318 studies from PubMed, 1421 studies from EMBASE, 445 studies from Web of Science™, 1 study from ClinicalTrials, 3 studies from ClinicalKey and 3 studies from Google scholar. Removal of duplicates left 1625 articles. Of those studies, 1587 were excluded after their titles and abstracts were screened. The remaining 38 studies were read in full for eligibility. No additional studies were found from the references of the retrieved studies. Fourteen studies were eliminated for the following reasons: 4 studies with concurrent treatment with non-antiplatelet drugs; 1 study not reporting the time from admission to surgery; 3 studies comparing non-antiplatelet medication; and 6 studies in which grouping did not meet the inclusion criteria. The reasons for exclusion are listed in Table 1 . Eventually, 24 studies were included in this review. Table 1 Excluded studies and reasons for exclusion Excluded studies Reasons for exclusion Manning et al. 2004 [ 42 ] This study did not report the time from admission to theatre. Harty et al. 2007 [ 43 ] Antiplatelet intervention group was with delayed surgery for more than 5 days Dettoni et al. 2011 [ 44 ] Both antiplatelet intervention group and control group were discontinued for more than 5 days before surgery Leonidou et al. 2011 [ 45 ] Antiplatelet intervention group was with delayed surgery for more than 5 days Nwachuku et al. 2011 [ 46 ] These groups were divided into early surgery group or delayed surgery group based on the time from admission to theatre less than or more than 48 hours. Lee et al. 2012 [ 47 ] The study compared non-antiplatelet medication Drescher et al. 2014 [ 48 ] The study compared non-antiplatelet medication Kulachote et al. 2015 [ 49 ] The intervention group was with non-antiplatelet drugs concurrently Akaoka et al. 2016 [ 50 ] The intervention group was with non-antiplatelet drugs concurrently Purushothaman et al. 2016 [ 51 ] These groups were divided into early surgery group or delayed surgery group based on the time from admission to theatre less than or more than 48 hours. Hwang et al. 2016 [ 52 ] The intervention group was with non-antiplatelet drugs concurrently Zhang et al. 2017 [ 53 ] Antiplatelet intervention group was with delayed surgery for more than 5 days Lott et al. 2018 [ 54 ] The intervention group was with non-antiplatelet drugs concurrently Hoerlyck et al. 2019 [ 55 ] The study compared non-antiplatelet medication Assessment of Study Quality No relevant randomized-controlled trials were detected; all of the included studies were comparative cohort studies in design. Therefore, the quality of the included studies was evaluated by the Newcastle/Ottawa scale (NOS).[ 10 ] Two investigators independently scored items and assessed bias blinded to the study outcome. For each item, different response options were available, and a star system was adopted to provide a semi-quantitative evaluation of study quality. The NOS range is between zero and nine stars. Studies within 4 stars are considered to be of low quality, while those with 5 or more stars will be selected. The characteristics of all the included studies are presented in Table 2 . Table 2 Characteristics of included studies in the meta-analysis. Study Country Study type Quality assessment Duration Sample size Groups Female (% ) Age (year) a Time to surgery (day) a Fracture type Concurrent antiplatelet or thromboprophylaxis Al Khudairy et al. 2013 [56] Ireland Cohort (Retrospective) **** * *** 24 months 47 Early VS delayed 66% 80.3(8.3) 4.2(1.0) VS 8.0(1.0) Intra and Extracapsular Unclear Chechik et al. 2012 [57] Israel Quasi-randomized (retrospective) **** * *** 34 months 60 Early VS delayed 50% 82.5(7.9) 1.67(1.0) VS 7.5(2.70) Intra and Extracapsular 33% in early group and 17% in delayed group on aspirin 40 mg LMWH for thromboprophylaxis Cox et al. 2009 [58] UK Cohort (Retrospective) **** _ ** 2 years 20 Early VS delayed 65% 80.9 1.1 VS 7 Intra and Extracapsular Chemical or mechanical thromboprophylaxis Johansen et al. 2008 [59] UK Cohort (Retrospective) **** _ ** 18 months 17 Early VS delayed Unclear Unclear 2.7 VS 7.3 Unclear Unclear Pailleret et al. 2017 [60] France Cohort (Retrospective) **** ** ** 6 years 39 Early VS delayed 77% 86(7.5) 1(1) VS 5(1) Intra and Extracapsular 24% in early group and 32% in delayed group on aspirin 40 mg LMWH for thromboprophylaxis Sa-Ngasoongsong et al. 2015 [61] Thailand Cohort (Prospective and retrospective) **** * *** 3 years 94 Early VS delayed 73% 80.5(8.0) 1.6(0.9) VS 8.9(3.6) Intra and Extracapsular 42 aspirin and 7 clopidogrel in early group, 36 aspirin and 9 clopidogrel in delayed group Yoo et al. 2015 [62] Korean Cohort (Retrospective) **** * *** 3 years 43 Early VS delayed 70% 73.0(7.1) < 1 days VS 5.7 Intracapsular Mechanical thromboprophylaxis was used and chemical prophylactic agents were not Sim et al. 2009 [63] Australia Cohort (Retrospective) **** * *** 44 months 135 1) Early VS delayed 2) Antiplatelet VS No antiplatelet 76% 80.7(9.7) 1) 5 days 2) 3.5(3.2) VS 0.9(0.8) Intra and Extracapsular Unclear Zehir et al. 2015 [14] Turkey Cohort (Retrospective) **** * *** 6 years 211 1) Early VS delayed 2) Antiplatelet VS No antiplatelet 55% 77.5(7.6) 1) 1.79 VS 5.82 2) 1.79 VS 1.68 Intracapsular 40 mg LMWH for thromboprophylaxis Anekstein et al. 2004 [64] Israel Cohort (Prospective) **** ** *** 14 months 104 Antiplatelet VS No antiplatelet Unclear 77.1(10.1) 1.53(0.9) VS 1.48(0.9) Intra and Extracapsular Unclear Chechik et al. 2011 [31] Israel Cohort (Prospective) **** * *** 21 months 88 Antiplatelet VS No antiplatelet 66% 81.8(7.4) 2.15(1.4) VS 1.88(1.1) Intra and Extracapsular Unclear Collinge et al. 2012 [65] USA Cohort (Retrospective) **** ** ** 5 years 946 Antiplatelet VS No antiplatelet 72% 80.8(8.7) 1.54(1.0) VS 1.55(0.9) Intra and Extracapsular A prophylactic doses of enoxaparin (Lovenox) within 24 hours after surgery Feely et al. 2013 [66] USA Cohort (Retrospective) **** ** *** 14 years and 6 months 120 Antiplatelet VS No antiplatelet 55% 82.2(8.4) 1.1(0.7) VS 1.3(1.3) Intra and Extracapsular 2 cohort had similar percentages of patients concurrent on aspirin and chemical thromboprophylaxis Ghanem et al. 2017 [67] USA Cohort (Retrospective) **** * ** 8 years 623 Antiplatelet VS No antiplatelet 69% 83.1 1.7 VS 1.3 Intracapsular 48% with aspirin in clopidogrel group, 38% in control group. A prophylaxis of enoxaparin was 22% in clopidogrel group and 30% in control group Ginsel et al. 2015 [68] Australia Cohort (Retrospective) **** * *** 1 year 300 Antiplatelet VS No antiplatelet 71% 81.6(13.1) 1.76 VS 1.6 Intracapsular Unclear Kennedy et al. 2006 [69] Ireland Cohort (Retrospective) **** _ ** NR 98 Antiplatelet VS No antiplatelet 73% 81.9 All patients < 2 days Intra and Extracapsular Unclear Kragh et al. 2011 [70] Sweden Cohort (Retrospective) **** * ** 2 years 255 Antiplatelet VS No antiplatelet 54% 82.4(8.8) 0.84(0.4) VS 0.8(0.4) Intra and Extracapsular 40 mg enoxaparin for thromboprophylaxis, 47% with compression bandage in antiplatelet group and 43% in non-antiplatelet group Thaler et al. 2010 [71] Austria Cohort (Prospective) **** * *** 27 months 462 Antiplatelet VS No antiplatelet 74% 78(11) 1.29(1.9) VS 1.3(2.0) Intra and Extracapsular 14% of clopidogrel group and 22% control group on aspirin. 40 mg enoxaparin for thromboprophylaxis. Clareus et al. 2015 [72] Sweden Cohort (Retrospective) **** ** *** 3 years 112 Antiplatelet VS No antiplatelet 68% 84.7(7.3) 1.67(1.2) VS 0.88(0.5) Intra and Extracapsular Unclear Hossain et al. 2013 [73] UK Cohort (Retrospective) **** ** ** 2 years 102 Antiplatelet VS No antiplatelet 81% 83.0(7.5) All patients < 2 days Intracapsular 32% of clopidogrel group and 44% control group on aspirin. 40 mg enoxaparin postoperatively for 6 weeks for thromboprophylaxis Manaqibwala et al. 2014 [74] USA Cohort (Retrospective) **** ** ** 7 years 162 Antiplatelet VS No antiplatelet 69% 84.1(8.9) 2.3(2.0) VS 1.9(2.9) Intracapsular 66.7% of clopidogrel group and 43.5% control group on aspirin. 40 mg enoxaparin or 5000 units heparin postoperatively for thromboprophylaxis Nydick et al. 2010 [75] USA Cohort (Retrospective) **** ** * 5 years 50 Antiplatelet VS No antiplatelet Unclear Unclear 1.81 VS 1.65 Intra and Extracapsular Unclear Wallace et al. 2012 [76] USA Cohort (Retrospective) **** ** *** over 5 years 110 Antiplatelet VS No antiplatelet 73% 79.9(9.1) All patients < 2 days Intra and Extracapsular Mechanical thromboprophylaxis was used and chemical prophylactic agents were not Wordsworth et al. 2013 [77] UK Cohort (Prospective) **** * *** 6 years 1225 Antiplatelet VS No antiplatelet 72% 82.3(9.4) 1.23 VS 1.20 Intra and Extracapsular 36.7% of clopidogrel group and 20% control group on aspirin. 40 mg enoxaparin postoperatively for 2-4 weeks for thromboprophylaxis a Values are mean (Standard Deviation) LMWH = low molecular weight heparin. A star system is used to allow a semi-quantitative assessment of study quality by using Newcastle/Ottawa scale. 5 or more stars for selection, _ = zero score for this domain. * = 1 point within this domain. Data Collection and Abstraction Two researchers independently extracted the data, including the title, lead author, publication year, country, study design, trial duration, number of participants, participant characteristics (mean age, gender, and fracture type), time to surgery, cohorts compared, surgical treatment, concurrent antiplatelet use and perioperative use of thromboprophylaxis. When the trials had more than 2 groups and allowed multiple comparisons, we only collected the relevant information and data reported in the original articles. The number of events was extracted for all dichotomous outcomes and means, and standard deviations (SDs) were extracted for all continuous outcomes. If these values were not available, they were indirectly derived from p values or confidence intervals, if possible. Outcomes were defined as a direct or indirect reflection of the surgical risk and prognosis of patients. All outcome data were extracted from included studies as far as possible. These included (1) in-hospital, 30-day, 3-month and 1-year mortality; (2) blood transfusion exposures; (3) the average blood transfusion unit per patient; (4) decreases in haemoglobin; (5) length of hospital stay; (6) reoperation rate; and (7) postoperative complications including acute coronary syndrome, cerebrovascular events, deep vein thrombosis, pulmonary embolism, wound-related complications (infection and haematoma) and major bleeding (major bleeding was defined according to Eriksson et al.[ 11 ] as follows: (1) fatal bleeding, (2) excessive bleeding resulting in an intraoperative transfusion of four or more units of red blood cells, (3) bleeding involved any critical organ, and (4) bleeding that led to reoperation. Meta-analysis Methodology Actually, the following two meta-analyses were performed on the identified studies: (1) studies comparing early surgery (< 5 days) in hip fracture patients with antiplatelet therapy versus those without antiplatelet therapy and (2) studies comparing early surgery ( 5 days) in patients with hip fractures receiving antiplatelet therapy. To evaluate whether there is a difference due to drugs between the antiplatelet and non-antiplatelet groups, we specified subgroups based on the antiplatelet treatment (aspirin, clopidogrel or the combination of aspirin and clopidogrel). If possible, data were used from patients only on one specified drug while not on other antiplatelet drugs. We performed a meta-analysis to calculate the odds ratios (ORs) or weighted mean differences (WMDs) presented with 95% confidence intervals (CIs) using the Mantel-Haenszel statistical method. According to the Cochrane Handbook,[ 12 ] trials with no events in either the intervention or control group were not included in the meta-analysis when ORs were calculated. The I 2 statistic was used to estimate the statistical heterogeneity between statistical data. A random-effects model was adopted when the heterogeneity was significant (p < 0.05), and a fixed-effects model was used if heterogeneity was absent. Publication bias was evaluated using funnel plots. Sensitivity analysis was performed by excluding studies without controlling for confounding variables or studies with characteristics different from the others. All meta-analyses were conducted using Review Manager 5.3, and p < 0.05 was regarded as statistically significant. Results Can early surgery be safely implemented on hip fracture patients who are treated with antiplatelet therapy? A total of 17 studies were included to compare early surgery for hip fracture patients treated with antiplatelet therapy with those without antiplatelet therapy. As shown in Table 3 , no significant differences in in-hospital mortality, 30-day mortality, or 1-year mortality were observed. However, there was substantial heterogeneity (p = 0.007; I 2 = 68%) and an asymmetric funnel plot for 1-year mortality, which may be due to the trial by Kragh et al.[ 13 ]; thus, a random-effects model was used for this meta-analysis. Sensitivity analysis revealed that there was no evidence of heterogeneity in the remaining studies (p = 0.45; I 2 = 0%), and it did not change the overall results when this outlier study was removed. Table 3 Outcomes of meta-analysis in early surgery for hip fracture patients with or without antiplatelet therapy and subgroup analysis based on different drug regimens Outcomes No. of Trials No. of Participants WMD or OR (95% CI) Subtotal P value Subtotal Heterogenicity (I 2 = %) P value between subgroup (I 2 = %) P value Antiplatelet Control In-hospital mortality Aspirin 3 11/456 24/1128 1.11 (0.54–2.32) 0.77 0 0.81 0.59 Clopidogrel 4 2/106 26/1242 1.17 (0.34–3.99) 0.80 0 Clopidogrel and aspirin 1 1/34 8/619 2.31 (0.28–19.05) 0.44 Not applicable 30-day mortality Aspirin 2 25/371 42/756 1.22 (0.72–2.07) 0.47 89 0.64 0.56 Clopidogrel 5 8/182 121/2070 1.20 (0.55–2.60) 0.65 0 Clopidogrel and aspirin 1 1/34 39/619 0.45 (0.06–3.38) 0.44 Not applicable 1-year mortality Aspirin 2 85/371 131/756 1.91 (0.56–6.54) 0.30 90 0.55 0.43 Clopidogrel 3 29/110 488/1534 0.90 (0.49–1.64) 0.72 41 Clopidogrel and aspirin 1 7/34 117/619 1.11 (0.47–2.62) 0.81 Not applicable Drop in hemoglobin Aspirin 4 450 879 0.12 (-0.06-0.31) 0.18 0 0.88 0.08 Clopidogrel 6 201 1017 0.16 (-0.10-0.42) 0.22 0 Clopidogrel and aspirin 1 34 619 0.00 (-0.58-0.58) 1.00 Not applicable Number of patients receiving blood transfusion Aspirin 4 253/450 465/879 1.16 (0.91–1.46) 0.23 0 0.39 0.03 Clopidogrel 10 118/361 875/2965 1.19 (0.90–1.59) 0.23 36 Clopidogrel and aspirin 1 24/34 337/619 2.01 (0.94–4.27) 0.07 Not applicable Mean number of units of blood transfused Aspirin 5 530 1185 0.13 (-0.13-0.40) 0.32 49 0.23 0.07 Clopidogrel 7 250 2487 0.15 (-0.25-0.56) 0.46 71 Clopidogrel and aspirin 2 49 641 0.69 (0.10–1.28) 0.02 0 Length of hospital stay Aspirin 2 380 808 -0.39 (-0.83-0.06) 0.09 0 0.03 0.76 Clopidogrel 6 257 1203 0.58 (-0.17-1.34) 0.13 0 Clopidogrel and aspirin 2 49 641 0.97 (-0.40-2.34) 0.17 0 Reoperation Aspirin 2 3/223 3/304 1.35 (0.28–6.61) 0.71 0 0.93 0.29 Clopidogrel 6 10/216 33/1037 1.47 (0.70–3.09) 0.31 0 Acute coronary syndrome Aspirin 1 8/118 5/137 1.92 (0.61–6.04) 0.26 Not applicable 0.52 0.004 Clopidogrel 6 14/240 19/984 2.27 (1.07–4.81) 0.03 0 Clopidogrel and aspirin 1 3/15 0/22 12.60 (0.60-264.14) 0.10 Not applicable Cerebrovascular events Aspirin 2 2/140 1/159 1.64 (0.27–9.79) 0.59 39 0.76 0.53 Clopidogrel 3 2/84 4/249 1.77 (0.35–9.04) 0.49 0 Clopidogrel and aspirin 1 0/15 1/22 0.46 (0.02–12.12) 0.64 Not applicable Deep venous thrombosis Aspirin 3 9/476 11/923 1.50 (0.58–3.84) 0.40 61 0.94 0.30 Clopidogrel 4 2/162 14/1435 1.60 (0.45–5.74) 0.47 0 Clopidogrel and aspirin 1 0/34 9/619 0.93 (0.05–16.33) 0.96 Not applicable Pulmonary embolism Aspirin 2 2/358 4/786 1.06 (0.22–5.14) 0.95 0 0.79 0.54 Clopidogrel 6 2/251 14/1664 1.37 (0.44–4.23) 0.59 0 Clopidogrel and aspirin 1 0/34 2/619 3.58 (0.17–76.02) 0.41 Not applicable Wound-related complications Aspirin 4 14/498 25/945 0.86 (0.44–1.69) 0.67 0 0.34 0.48 Clopidogrel 8 14/287 35/2398 1.52 (0.75–3.09) 0.24 0 Clopidogrel and aspirin 2 2/49 10/641 2.60 (0.49–13.74) 0.26 0 Major bleeding Aspirin 1 3/98 10/342 1.05 (0.28–3.89) 0.94 Not applicable 0.58 0.48 Clopidogrel 3 5/91 13/444 1.75 (0.52–5.91) 0.37 0 We found that antiplatelet therapy was significantly associated with an increase in the number of transfused patients (OR = 1.21; 95% CI, 1.01–1.44; p = 0.03). No evidence of statistical heterogeneity or publication bias was detected. Although the analysis of the three subgroups showed no differences in the transfusion rate, we focused on the overall results rather than on a separate subgroup because a test for interaction yielded a p value of 0.39. There were no significant differences in the decline in haemoglobin or mean number of units of blood transfused between the two groups despite the increase in the transfusion rate. Moderate statistical heterogeneity (p = 0.002; I 2 = 61%) was observed for the mean number of units for transfusion, and a random-effect model was applied. Subgroup analysis showed that the combination of aspirin and clopidogrel may result in an increase in the mean number of units for transfusion (WMD = 0.69; 95% CI, 0.10–1.28; p = 0.02). Sensitivity analysis was performed by excluding Zehir et al.[ 14 ], which was the primary source of statistical heterogeneity. This may be because in this study, the preoperative haemoglobin levels of the antiplatelet group were significantly lower than that of the control group. Following removal of this study, a remarkable decrease in heterogeneity (p = 0.08; I 2 = 37%) was observed and the overall results remained unchanged. There was also no significant difference in the length of hospital stay, reoperation, cerebrovascular events, deep vein thrombosis, pulmonary embolism, major bleeding, or other wound-related complications between the antiplatelet and non-antiplatelet groups, except for acute coronary syndrome (OR = 2.41; 95% CI, 1.32–4.42; p = 0.004). Subgroup analysis suggested that the results did not change due to treatment with aspirin, clopidogrel or a combination of aspirin and clopidogrel. None of them showed significant heterogeneity or publication bias. Which is better, early or delayed surgery on hip fracture patients with antiplatelet therapy? A total of 9 studies were included to compare early surgery ( 5 days) for hip fracture patients treated with antiplatelet therapy upon admission. There was a significant decrease in mortality (OR = 0.43; 95% CI, 0.23–0.79; p = 0.006) for those treated with antiplatelet therapy with early surgery (Fig. 2 ). No evidence of statistical heterogeneity or publication bias was observed. Sensitivity analysis did not change the overall results. Subgroup analysis revealed that the point estimate regarding the association of delayed surgery and mortality at any time point was increased, but only 3-month mortality reached statistical significance. Early surgery was significantly associated with increased haemoglobin loss in hip fracture patients who received antiplatelet drugs (WMD = 0.75; 95% CI, 0.50-1.00; p < 0.001) (Fig. 3 ). However, there were no significant differences in the number of blood transfusions (Fig. 4 ) or mean number of units for transfusion (Fig. 5 ). There was remarkable statistical heterogeneity (p = 0.01; I 2 = 72%) and possible publication bias for the mean number of units for transfusion. Sensitivity analysis was performed by separately excluding Zehir et al[ 14 ], and the results remained unchanged. The length of hospital stay in the early surgery group was significantly shortened (WMD = -6.05; 95% CI, -7.06-5.04; p < 0.001) (Fig. 6 ). Nevertheless, there were no significant differences for acute coronary syndrome, cerebrovascular events, deep vein thrombosis, pulmonary embolism, major bleeding or other wound-related complications (Fig. 7 ). Moreover, no heterogeneity was observed, and the results were not altered by separately excluding subgroups after sensitivity analysis. Discussion Hip fracture patients tend to be older, with a high mortality rate, and their quality of life is seriously affected.[ 15 ] As the global elderly population is gradually increasing, the number of elderly patients with hip fractures and the socioeconomic burden are also increasing year by year.[ 16 , 17 ] Most of them usually suffer from cardio-cerebrovascular disease and need antiplatelet therapy. Some believe that it is necessary to withhold antiplatelet therapy to promote platelet function recovery and reduce the risk of perioperative bleeding. Others believe that surgery should be performed as soon as possible without stopping medication. Previous literature has found that there is an absence of a consensus or policies for the treatment of patients who sustain hip fractures while on antiplatelet therapy. A telephone questionnaire data analysis about current practical measures among 110 orthopaedics in the UK showed that 56.4% of orthopaedics did not have a standard of clopidogrel withdrawal, and the remaining 43.6% stopped clopidogrel before surgery. Among them, 20.9% of the surgeries were delayed by more than 5 days, and 12.7% were delayed by 7–10 days.[ 18 ] Although Soo et al.[ 19 ] and Doleman et al.[ 20 ] tried to identify how to manage these cases, the total numbers of studies included in these reviews were low, and these studies may result in type II errors and were either limited to one specific antiplatelet drug or confused the presence or absence of antiplatelet drugs with early or delayed surgery. Thus, we performed a more systematic and specific search and analysis to address the issues highlighted from previous research. The important finding of our study is that early surgery for hip fracture patients taking antiplatelet drugs might promote a higher risk of bleeding and more blood transfusion requirements compared to those without antiplatelet therapy. Nevertheless, there were no significant differences in prognosis. Instead, delayed intervention will lead to higher mortality and a longer hospital stay. There were several limitations to our study. One of the limitations was that the methodological quality of the studies included was not optimal. Only observational studies were included in our analysis, which means that only the inference of association is possible rather than causality; there may be potential confounding variables that bias the outcomes. For instance, there were three main types of hip fracture surgery in included studies: hip repair using internal fixation, partial hip replacement surgery, and total hip replacement surgery. Different surgical methods will affect the outcomes, but most of the included studies did not distinguish and explain so that we were unable to exclude this confounding factor. As expected, the intervention groups in most studies[ 13 , 21 – 26 ] showed a significant increase in the number of cardiovascular or cerebrovascular comorbidities; however, surprisingly, only three of them showed a significant difference in the ASA grade.[ 13 , 23 , 25 ] Moreover, the preoperative haemoglobin values of the intervention group in five studies[ 14 , 25 , 27 , 28 ] were significantly lower than those of the control group, which may potentially influence blood transfusions, meaning that the intervention groups required more units of blood. This may be why Zehir et al.[ 14 ] was the main source of heterogeneity in the outcomes for the mean number of units for transfusion. A further limitation was that publication bias existed in some studies as shown in the funnel plots; this might because the number of included trials was less than 10. Finally, although we performed subgroup analysis based on the types of antiplatelet drugs and data were used from patients on one specific drug and not on the others simultaneously as much as possible, most of the trials included patients concurrently treated with aspirin in the clopidogrel subgroup, and this may affect the final results. Regarding whether early surgery is safe for hip fracture patients taking antiplatelet drugs, the number of patients transfused in the antiplatelet group increased statistically, which was consistent with that in cardiac surgery.[ 29 , 30 ] However, we found no convincing evidence of an increase in the average blood transfusion demands, except for in the medicine-united group. This suggested that there might indeed be an increased risk of bleeding in intraoperative blood loss or hidden blood loss, especially when antiplatelet drugs are used in combination.[ 31 ] However, because of the concerns of antiplatelets from anaesthesiologists and physicians, the patients taking antiplatelet drugs are more likely to have a lower threshold to receive transfusions. No differences in mortality, duration of hospital stay, reoperation rate or related complications, except acute coronary syndrome, was detected between the two groups. The presence of more vascular comorbidities in the antiplatelet group of most studies may be responsible for the significant increase in acute coronary syndrome. Regarding whether early or delayed surgery is better for patients with hip fractures on antiplatelet therapy, early surgery was associated with a greater decrease in haemoglobin; however, there were no differences in the transfusion rate or mean number of units for transfusion. This also supports the fact that patients taking antiplatelet drugs are more likely to be transfused owing to potential performance bias. Multiple studies have shown that delays in surgery for more than 2 days for hip fracture patients are closely related to an increased risk of complications due to long-term bedridden and delayed mobilization.[ 32 , 33 ] Early surgical intervention can significantly reduce postoperative mortality and morbidity, promote a shorter hospital stay, and prompt patients to return to pre­injury ambulation status.[ 34 – 38 ] However, early surgery for patients on antiplatelet may cause haemorrhagic accidents, as platelet function has not fully recovered[ 39 ] In our study, delayed surgery increased the risk of mortality, and subgroup analysis showed that the point estimate regarding mortality at any time point was increased, especially mortality at 30 days and 3 months, which showed significant differences. Furthermore, hip fractures are more likely to prolong the length of hospital stay than any other musculoskeletal injuries, accounting for more than two-thirds of all hospital stays caused by fractures.[ 40 ] Early surgery can effectively shorten the length of hospital stay and reduce social and economic burdens. Unlike previous research studies, our study suggests that there are no differences in the incidence of postoperative complications between early and delayed surgery. Previous studies have demonstrated that sudden withdrawal will lead to conversion to a prothrombotic and proinflammatory condition, which may complicate surgery and lead to adverse clinical events, such as recurrence and death by myocardial infarction, which has already been stabilized by drugs or stents.[ 41 ] However, in the meta-analysis reported here, subgroup analysis showed that a surgical delay did not have a higher postoperative incidence of cardiocerebrovascular events or thromboembolic events, and early surgery did not result in a higher incidence of severe bleeding. Conclusion In conclusion, our analysis of 24 trials including a total of 5423 patients suggests that early surgery can be safely performed on hip fracture patients receiving antiplatelet drugs upon admission. Current evidence shows that although early surgery carries a high risk of bleeding, it does not lead to substantial blood transfusion demands or haemorrhagic events. Furthermore, compared with delayed surgery, early surgical intervention is associated with a significant decrease in mortality (p = 0.006) and length of hospital stay (p < 0.001). Based on the available evidence, it is unnecessary to delay surgery to restore platelet function when patients with hip fractures receive antiplatelet therapy. Early surgery can significantly reduce mortality and hospital stay, which is conducive to patient recovery. Further large-scale, multi-centred, well-motivated and well-designed randomized trials are required to confirm these findings and develop clearer guidelines for the treatment of these patients. Declarations Abbreviations PRISMA: Preferred Reporting Items for Systematic Review and Meta-Analysis statement; NOS: Newcastle/Ottawa scale; SDs: Standard deviations; ORs: Odds ratios; WMDs: Weighted mean differences; CIs: Confidence intervals. Ethics approval and consent to participate This article does not contain any studies with human participants or animals performed by any of the authors. Consent for publication Not applicable. Availability of data and materials All data generated or analyzed during this study are included in published articles. Competing interests The authors declare that they have no competing interests. Funding None. Authors' contributions JDN and ZYY contributed to the conception and design of the study. ZYY performed the statistical analysis and drafted the manuscript. ZL and LTK contributed to the literature search and study selection. LTK and YQG contributed to the quality assessment. YQG and SBT contributed to the data extraction. SBT contributed to the revisions of the manuscript. All authors read and approved the final manuscript. Acknowledgements We thank the authors of the included studies for their help. References Morris AH, Zuckerman JD. 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Supplementary Files Additionalfiles1.docx Cite Share Download PDF Status: Published Journal Publication published 12 Mar, 2020 Read the published version in Journal of Orthopaedic Surgery and Research → Version 1 posted Review # 2 received at journal 03 Mar, 2020 Editorial decision: Accept 03 Mar, 2020 Reviewer # 2 agreed at journal 20 Feb, 2020 Reviewer # 1 agreed at journal 18 Feb, 2020 Review # 1 received at journal 18 Feb, 2020 Reviewers invited by journal 08 Feb, 2020 Submission checks completed at journal 07 Feb, 2020 Editor assigned by journal 07 Feb, 2020 Editor invited by journal 06 Feb, 2020 First submitted to journal 05 Feb, 2020 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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2","display":"","copyAsset":false,"role":"figure","size":60668,"visible":true,"origin":"","legend":"Meta-analysis of early surgery group and delayed surgery group: mortality.","description":"","filename":"FigurePage2.png","url":"https://assets-eu.researchsquare.com/files/a1a1396b-8848-4bef-a322-b9d2150aad9c/v1/Figure_Page_2.png"},{"id":475040,"identity":"72491f31-3654-436f-9ddd-93bca29888e5","added_by":"auto","created_at":"2020-02-11 05:51:05","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":34708,"visible":true,"origin":"","legend":"Meta-analysis of early surgery group and delayed surgery group: decrease in haemoglobin concentration.","description":"","filename":"FigurePage3.png","url":"https://assets-eu.researchsquare.com/files/a1a1396b-8848-4bef-a322-b9d2150aad9c/v1/Figure_Page_3.png"},{"id":475041,"identity":"e7a66d6e-3789-42c6-b488-a6232d1a0ab7","added_by":"auto","created_at":"2020-02-11 05:51:05","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":33883,"visible":true,"origin":"","legend":"Meta-analysis of early surgery group and delayed surgery group: transfusion exposures.","description":"","filename":"FigurePage4.png","url":"https://assets-eu.researchsquare.com/files/a1a1396b-8848-4bef-a322-b9d2150aad9c/v1/Figure_Page_4.png"},{"id":475042,"identity":"6a0ec307-4c9a-497e-9789-00835801c0c8","added_by":"auto","created_at":"2020-02-11 05:51:05","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":36065,"visible":true,"origin":"","legend":"Meta-analysis of early surgery group and delayed surgery group: mean number of units of blood transfused.","description":"","filename":"FigurePage5.png","url":"https://assets-eu.researchsquare.com/files/a1a1396b-8848-4bef-a322-b9d2150aad9c/v1/Figure_Page_5.png"},{"id":475043,"identity":"fc1cfd74-ace5-465e-b867-8ac3beae7831","added_by":"auto","created_at":"2020-02-11 05:51:05","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":36614,"visible":true,"origin":"","legend":"Meta-analysis of early surgery group and delayed surgery group: length of hospital stay.","description":"","filename":"FigurePage6.png","url":"https://assets-eu.researchsquare.com/files/a1a1396b-8848-4bef-a322-b9d2150aad9c/v1/Figure_Page_6.png"},{"id":475044,"identity":"2953043f-0aa3-4368-b199-21d7957d2b91","added_by":"auto","created_at":"2020-02-11 05:51:05","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":78719,"visible":true,"origin":"","legend":"Meta-analysis of early surgery group and delayed surgery group: postoperative complications.","description":"","filename":"FigurePage7.png","url":"https://assets-eu.researchsquare.com/files/a1a1396b-8848-4bef-a322-b9d2150aad9c/v1/Figure_Page_7.png"},{"id":14033958,"identity":"c39df798-364b-49fd-aa1e-76d9c2312be8","added_by":"auto","created_at":"2021-09-27 18:29:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1227912,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-13604/v1/dd65aa8d-3cac-4de1-a1ce-d9789d319536.pdf"},{"id":475037,"identity":"3d6b91ca-4ea4-4f47-94e3-98ee26e0eca4","added_by":"auto","created_at":"2020-02-11 05:51:04","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":17688,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfiles1.docx","url":"https://assets-eu.researchsquare.com/files/a1a1396b-8848-4bef-a322-b9d2150aad9c/v1/Additional files 1.docx"}],"financialInterests":"","formattedTitle":"Is hip fracture surgery safe for patients on antiplatelet drugs and is it necessary to delay surgery? A Systematic Review and Meta-analysis","fulltext":[{"header":"Background","content":"\u003cp\u003eHip fractures are among the main causes of orthopaedic surgical admissions and life-threatening injuries that occur worldwide, mainly in elderly individuals. Older patients are particularly vulnerable to sustaining hip fractures because of the high prevalence of osteoporosis or osteopenia. According to the American Academy of Orthopaedic Surgeons, each year, the number of hospital admissions due to hip fractures can reach up to 350,000.[1] By the year 2040, there will be more than 500,000 people with hip fractures per year, with an annual medical expenditure of at least $9.8 billion.[1,2] Although the development of surgical instruments and medical technology for early mobilization has advanced significantly, the mortality rate remains high. The cause of this high mortality rate is not entirely clear, and most of the deaths are ascribed to comorbidities, including cardiovascular disease.[3,4] Antiplatelet drugs are simultaneously used in most hip fracture patients for primary and secondary prevention of cardiovascular or cerebrovascular events. Because the inhibitory action of drugs on platelets is irreversible and mature platelets do not synthesize new proteins, antiplatelet drugs make platelets ineffective for approximately seven days, the mean lifetime of a platelet.[5]\u003c/p\u003e\n\u003cp\u003eDespite the obvious advantages in the prevention and treatment of cardiovascular diseases, the continued use of antiplatelet drugs perioperatively may have great risks. Clopidogrel therapy in cardiac surgery without preoperative disruption increased haemorrhagic risks, transfusion demands and infection with a poor prognosis.[6] The potential haematoma risk in orthopaedic surgery[7] forces withdrawal of antiplatelet drugs and delays surgery for at least 5 days to allow platelet function to return to an adequate status. Currently, no agreed upon guidelines exist for the appropriate surgical time for patients suffering hip fractures while on antiplatelet therapy, and there is a marked divergence of opinion on the final results of early and delayed surgical intervention.[8]\u003c/p\u003e\n\u003cp\u003eTherefore, the purpose of this review was to identify whether early surgical intervention can be safely implemented on patients who develop hip fractures while on antiplatelet therapy to promote satisfactory outcomes. A secondary aim was to determine whether early or delayed surgery was more appropriate for those patients. Moreover, we attempt to establish a framework for managing hip fracture patients with antiplatelet therapy.\u003c/p\u003e"},{"header":"Methods","content":" \u003ch2\u003eLiterature Search\u003c/h2\u003e \u003cp\u003eThis review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis statement (PRISMA).[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] The following databases were fully searched from their inception date to January 2020: PubMed, EMBASE, the Cochrane Library, Web of Science\u0026trade;, ClinicalTrials, ClinicalKey and Google Scholar. For each database, a specific search strategy was developed using the following keywords: \u0026ldquo;Hip AND Fracture\u0026rdquo;, \u0026ldquo;Antiplatelet\u0026rdquo;, \u0026ldquo;Antithrombocyte\u0026rdquo;, \u0026ldquo;Platelet aggregation inhibitors\u0026rdquo;, \u0026ldquo;Aspirin\u0026rdquo;, \u0026ldquo;Plavix\u0026rdquo;, and \u0026ldquo;Clopidogrel\u0026rdquo; (detailed search strategies as shown in Additional files 1). Searches were without date or geographic restriction but were limited to primary studies written in English. All references of retrieved articles were also checked for additional relevant studies.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eInclusion and Exclusion Criteria\u003c/h2\u003e \u003cp\u003eStudies were included according to the following inclusion criteria: (1) randomized-controlled trials or high-quality observational studies; (2) studies that compared the use of antiplatelet drugs on admission with placebo or no treatment in hip fracture patients undergoing early surgery (the time from admission to theatre\u0026thinsp;\u0026lt;\u0026thinsp;5 days); and (3) studies that compared early surgery (\u0026lt;\u0026thinsp;5 days) with delayed surgery (\u0026gt;\u0026thinsp;5 days) for patients suffering hip fractures while on antiplatelet therapy. Based on previous studies and half-life of antiplatelet drugs, we set 5 days as the dividing line. The exclusion criteria were as follows: (1) studies comparing non-antiplatelet medication, such as warfarin or low molecular weight heparin; (2) non-clinical studies such as basic science studies, narrative reviews, surveys, letters, editorials, case series, case reports, comments, conference abstracts or expert opinions; and (3) non-English studies. The potential overlap of subjects was evaluated by comparing demographic characteristics when multiple studies were conducted by the same author or research institute. Titles and abstracts were filtered and evaluated independently in a non-blinded standardized pattern. A final decision was made based on the adherence to the inclusion and exclusion criteria. Divergence was resolved by consensus.\u003c/p\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, from the search, 2328 potentially eligible records were identified (including duplicates), 137 studies from The Cochrane Library, 318 studies from PubMed, 1421 studies from EMBASE, 445 studies from Web of Science\u0026trade;, 1 study from ClinicalTrials, 3 studies from ClinicalKey and 3 studies from Google scholar. Removal of duplicates left 1625 articles. Of those studies, 1587 were excluded after their titles and abstracts were screened. The remaining 38 studies were read in full for eligibility. No additional studies were found from the references of the retrieved studies. Fourteen studies were eliminated for the following reasons: 4 studies with concurrent treatment with non-antiplatelet drugs; 1 study not reporting the time from admission to surgery; 3 studies comparing non-antiplatelet medication; and 6 studies in which grouping did not meet the inclusion criteria. The reasons for exclusion are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Eventually, 24 studies were included in this review.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eExcluded studies and reasons for exclusion\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eExcluded studies\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eReasons for exclusion\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eManning et al. 2004 [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eThis study did not report the time from admission to theatre.\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eHarty et al. 2007 [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eAntiplatelet intervention group was with delayed surgery for more than 5 days\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eDettoni et al. 2011 [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eBoth antiplatelet intervention group and control group were discontinued for more than 5 days before surgery\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eLeonidou et al. 2011 [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eAntiplatelet intervention group was with delayed surgery for more than 5 days\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNwachuku et al. 2011 [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eThese groups were divided into early surgery group or delayed surgery group based on the time from admission to theatre less than or more than 48 hours.\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eLee et al. 2012 [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eThe study compared non-antiplatelet medication\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eDrescher et al. 2014 [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eThe study compared non-antiplatelet medication\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eKulachote et al. 2015 [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eThe intervention group was with non-antiplatelet drugs concurrently\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAkaoka et al. 2016 [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eThe intervention group was with non-antiplatelet drugs concurrently\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePurushothaman et al. 2016 [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eThese groups were divided into early surgery group or delayed surgery group based on the time from admission to theatre less than or more than 48 hours.\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eHwang et al. 2016 [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eThe intervention group was with non-antiplatelet drugs concurrently\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eZhang et al. 2017 [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eAntiplatelet intervention group was with delayed surgery for more than 5 days\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eLott et al. 2018 [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eThe intervention group was with non-antiplatelet drugs concurrently\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eHoerlyck et al. 2019 [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eThe study compared non-antiplatelet medication\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eAssessment of Study Quality\u003c/h2\u003e \u003cp\u003eNo relevant randomized-controlled trials were detected; all of the included studies were comparative cohort studies in design. Therefore, the quality of the included studies was evaluated by the Newcastle/Ottawa scale (NOS).[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Two investigators independently scored items and assessed bias blinded to the study outcome. For each item, different response options were available, and a star system was adopted to provide a semi-quantitative evaluation of study quality. The NOS range is between zero and nine stars. Studies within 4 stars are considered to be of low quality, while those with 5 or more stars will be selected. The characteristics of all the included studies are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \n\u003cp\u003eTable 2\u003c/p\u003e\n\u003cp\u003eCharacteristics of included studies in the meta-analysis.\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eStudy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eCountry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eStudy type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003eQuality assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eDuration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003eSample size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003eFemale (% )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eAge (year)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eTime to surgery (day)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eFracture type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eConcurrent antiplatelet or thromboprophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eAl Khudairy et al. 2013\u0026nbsp;[56]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eIreland\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** * ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eEarly VS delayed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e66%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e80.3(8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e4.2(1.0) VS 8.0(1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eChechik et al. 2012\u0026nbsp;[57]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eIsrael\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eQuasi-randomized (retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** * ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e34 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eEarly VS delayed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e50%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e82.5(7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1.67(1.0) VS 7.5(2.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003e33% in early group and 17% in delayed group on aspirin\u003c/p\u003e\n \u003cp\u003e40 mg LMWH for thromboprophylaxis \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eCox et al. 2009\u0026nbsp;[58]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eUK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** _ **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e2 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eEarly VS delayed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e65%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e80.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1.1 VS 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eChemical or mechanical thromboprophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eJohansen et al. 2008\u0026nbsp;[59]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eUK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** _ **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e18 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eEarly VS delayed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e2.7 VS 7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003ePailleret et al. 2017\u0026nbsp;[60]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eFrance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** ** **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e6 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eEarly VS delayed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e77%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e86(7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1(1) VS 5(1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003e24% in early group and 32% in delayed group on aspirin\u003c/p\u003e\n \u003cp\u003e40 mg LMWH for thromboprophylaxis \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eSa-Ngasoongsong et al. 2015\u0026nbsp;[61]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eThailand\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Prospective and retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** * ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e3 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eEarly VS delayed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e73%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e80.5(8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1.6(0.9) VS 8.9(3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003e42 aspirin and 7 clopidogrel in early group, 36 aspirin and 9 clopidogrel in delayed group\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eYoo et al. 2015\u0026nbsp;[62]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eKorean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** * ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e3 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eEarly VS delayed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e70%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e73.0(7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e\u0026lt; 1 days VS 5.7\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eMechanical thromboprophylaxis was used and chemical prophylactic agents were not\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eSim et al. 2009\u0026nbsp;[63]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eAustralia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** * ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e44 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003e1) Early VS delayed\u003c/p\u003e\n \u003cp\u003e2) Antiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e76%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e80.7(9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1) \u0026lt; 5 days VS \u0026gt;5 days\u003c/p\u003e\n \u003cp\u003e2) 3.5(3.2) VS 0.9(0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eZehir et al. 2015\u0026nbsp;[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eTurkey\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** * ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e6 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003e1) Early VS delayed\u003c/p\u003e\n \u003cp\u003e2) Antiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e55%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e77.5(7.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1) 1.79 VS 5.82\u003c/p\u003e\n \u003cp\u003e2) 1.79 VS 1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003e40 mg LMWH for thromboprophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eAnekstein et al. 2004\u0026nbsp;[64]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eIsrael\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Prospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** ** ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e14 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e77.1(10.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1.53(0.9) VS 1.48(0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eChechik et al. 2011\u0026nbsp;[31]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eIsrael\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Prospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** * ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e21 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e66%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e81.8(7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e2.15(1.4) VS 1.88(1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003e\u0026nbsp;Unclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eCollinge et al. 2012\u0026nbsp;[65]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** ** **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e946\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e72%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e80.8(8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1.54(1.0) VS 1.55(0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eA prophylactic doses of enoxaparin (Lovenox) within 24 hours after surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eFeely et al. 2013\u0026nbsp;[66]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** ** ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e14 years and 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e55%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e82.2(8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1.1(0.7) VS 1.3(1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003e2 cohort had similar percentages of patients concurrent on aspirin and chemical thromboprophylaxis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eGhanem et al. 2017\u0026nbsp;[67]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** * **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e8 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e623\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e69%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e83.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1.7 VS 1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003e48% with aspirin in clopidogrel group, 38% in control group. A prophylaxis of enoxaparin was 22% in clopidogrel group and 30% in control group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eGinsel et al. 2015\u0026nbsp;[68]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eAustralia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** * ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e71%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e81.6(13.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1.76 VS 1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eKennedy et al. 2006\u0026nbsp;[69]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eIreland\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** _ **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e73%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e81.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eAll patients \u0026lt; 2 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eKragh et al. 2011\u0026nbsp;[70]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eSweden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** * **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e2 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e255\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e54%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e82.4(8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e0.84(0.4) VS 0.8(0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003e40 mg enoxaparin for thromboprophylaxis, 47% with compression bandage in antiplatelet group and 43% in non-antiplatelet group\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eThaler et al. 2010\u0026nbsp;[71]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eAustria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Prospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** * ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e27 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e462\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e74%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e78(11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1.29(1.9) VS 1.3(2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003e14% of clopidogrel group and 22% control group on aspirin. 40 mg enoxaparin for thromboprophylaxis.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eClareus et al. 2015\u0026nbsp;[72]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eSweden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** ** ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e3 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e68%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e84.7(7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1.67(1.2) VS 0.88(0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eHossain et al. 2013\u0026nbsp;[73]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eUK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** ** **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e2 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e81%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e83.0(7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eAll patients \u0026lt; 2 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003e32% of clopidogrel group and 44% control group on aspirin.\u003c/p\u003e\n \u003cp\u003e40 mg enoxaparin postoperatively for 6 weeks for thromboprophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eManaqibwala et al. 2014\u0026nbsp;[74]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** ** **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e7 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e162\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e69%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e84.1(8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e2.3(2.0) VS 1.9(2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003e66.7% of clopidogrel group and 43.5% control group on aspirin.\u003c/p\u003e\n \u003cp\u003e40 mg enoxaparin or 5000 units heparin postoperatively for thromboprophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eNydick et al. 2010\u0026nbsp;[75]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** ** *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1.81 VS 1.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eWallace et al. 2012\u0026nbsp;[76]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Retrospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** ** ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eover 5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e73%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e79.9(9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eAll patients \u0026lt; 2 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003eMechanical thromboprophylaxis was used and chemical prophylactic agents were not\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.737827715355806%\"\u003e\n \u003cp\u003eWordsworth et al. 2013\u0026nbsp;[77]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003eUK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.58052434456929%\"\u003e\n \u003cp\u003eCohort (Prospective)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.116104868913857%\"\u003e\n \u003cp\u003e**** * ***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e6 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e1225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.801498127340825%\"\u003e\n \u003cp\u003eAntiplatelet VS No antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.337078651685394%\"\u003e\n \u003cp\u003e72%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.179775280898877%\"\u003e\n \u003cp\u003e82.3(9.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003e1.23 VS 1.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.9588014981273405%\"\u003e\n \u003cp\u003eIntra and Extracapsular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.853932584269664%\"\u003e\n \u003cp\u003e36.7% of clopidogrel group and 20% control group on aspirin.\u003c/p\u003e\n \u003cp\u003e40 mg enoxaparin postoperatively for 2-4 weeks for thromboprophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eValues are mean (Standard Deviation)\u003c/p\u003e\n\u003cp\u003eLMWH = low molecular weight heparin.\u003c/p\u003e\n\u003cp\u003eA star system is used to allow a semi-quantitative assessment of study quality by using Newcastle/Ottawa scale. 5 or more stars for selection, _ = zero score for this domain. * = 1 point within this domain.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData Collection and Abstraction\u003c/h2\u003e \u003cp\u003eTwo researchers independently extracted the data, including the title, lead author, publication year, country, study design, trial duration, number of participants, participant characteristics (mean age, gender, and fracture type), time to surgery, cohorts compared, surgical treatment, concurrent antiplatelet use and perioperative use of thromboprophylaxis. When the trials had more than 2 groups and allowed multiple comparisons, we only collected the relevant information and data reported in the original articles. The number of events was extracted for all dichotomous outcomes and means, and standard deviations (SDs) were extracted for all continuous outcomes. If these values were not available, they were indirectly derived from p values or confidence intervals, if possible.\u003c/p\u003e \u003cp\u003eOutcomes were defined as a direct or indirect reflection of the surgical risk and prognosis of patients. All outcome data were extracted from included studies as far as possible. These included (1) in-hospital, 30-day, 3-month and 1-year mortality; (2) blood transfusion exposures; (3) the average blood transfusion unit per patient; (4) decreases in haemoglobin; (5) length of hospital stay; (6) reoperation rate; and (7) postoperative complications including acute coronary syndrome, cerebrovascular events, deep vein thrombosis, pulmonary embolism, wound-related complications (infection and haematoma) and major bleeding (major bleeding was defined according to Eriksson et al.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] as follows: (1) fatal bleeding, (2) excessive bleeding resulting in an intraoperative transfusion of four or more units of red blood cells, (3) bleeding involved any critical organ, and (4) bleeding that led to reoperation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eMeta-analysis Methodology\u003c/h2\u003e \u003cp\u003eActually, the following two meta-analyses were performed on the identified studies: (1) studies comparing early surgery (\u0026lt;\u0026thinsp;5 days) in hip fracture patients with antiplatelet therapy versus those without antiplatelet therapy and (2) studies comparing early surgery (\u0026lt;\u0026thinsp;5 days) versus delayed surgery (\u0026gt;\u0026thinsp;5 days) in patients with hip fractures receiving antiplatelet therapy. To evaluate whether there is a difference due to drugs between the antiplatelet and non-antiplatelet groups, we specified subgroups based on the antiplatelet treatment (aspirin, clopidogrel or the combination of aspirin and clopidogrel). If possible, data were used from patients only on one specified drug while not on other antiplatelet drugs.\u003c/p\u003e \u003cp\u003eWe performed a meta-analysis to calculate the odds ratios (ORs) or weighted mean differences (WMDs) presented with 95% confidence intervals (CIs) using the Mantel-Haenszel statistical method. According to the Cochrane Handbook,[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] trials with no events in either the intervention or control group were not included in the meta-analysis when ORs were calculated. The I\u003csup\u003e2\u003c/sup\u003e statistic was used to estimate the statistical heterogeneity between statistical data. A random-effects model was adopted when the heterogeneity was significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and a fixed-effects model was used if heterogeneity was absent. Publication bias was evaluated using funnel plots. Sensitivity analysis was performed by excluding studies without controlling for confounding variables or studies with characteristics different from the others. All meta-analyses were conducted using Review Manager 5.3, and p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was regarded as statistically significant.\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":" \u003ch2\u003eCan early surgery be safely implemented on hip fracture patients who are treated with antiplatelet therapy?\u003c/h2\u003e \u003cp\u003eA total of 17 studies were included to compare early surgery for hip fracture patients treated with antiplatelet therapy with those without antiplatelet therapy. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, no significant differences in in-hospital mortality, 30-day mortality, or 1-year mortality were observed. However, there was substantial heterogeneity (p\u0026thinsp;=\u0026thinsp;0.007; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;68%) and an asymmetric funnel plot for 1-year mortality, which may be due to the trial by Kragh et al.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]; thus, a random-effects model was used for this meta-analysis. Sensitivity analysis revealed that there was no evidence of heterogeneity in the remaining studies (p\u0026thinsp;=\u0026thinsp;0.45; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%), and it did not change the overall results when this outlier study was removed.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eOutcomes of meta-analysis in early surgery for hip fracture patients with or without antiplatelet therapy and subgroup analysis based on different drug regimens\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eOutcomes\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo. of Trials\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo. of Participants\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eWMD or OR (95% CI)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eSubtotal P value\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eSubtotal Heterogenicity (I\u003csup\u003e2\u003c/sup\u003e = %)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eP value between subgroup (I\u003csup\u003e2\u003c/sup\u003e = %)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eP value\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eAntiplatelet\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eControl\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eIn-hospital mortality\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e11/456\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e24/1128\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.11 (0.54\u0026ndash;2.32)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.77\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.81\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.59\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2/106\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e26/1242\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.17 (0.34\u0026ndash;3.99)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.80\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel and aspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1/34\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e8/619\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e2.31 (0.28\u0026ndash;19.05)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.44\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eNot applicable\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e30-day mortality\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e25/371\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e42/756\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.22 (0.72\u0026ndash;2.07)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.47\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e89\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.64\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.56\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e8/182\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e121/2070\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.20 (0.55\u0026ndash;2.60)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.65\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel and aspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1/34\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e39/619\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.45 (0.06\u0026ndash;3.38)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.44\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eNot applicable\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e1-year mortality\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e85/371\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e131/756\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.91 (0.56\u0026ndash;6.54)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.30\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e90\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.55\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.43\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e29/110\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e488/1534\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.90 (0.49\u0026ndash;1.64)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.72\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e41\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel and aspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e7/34\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e117/619\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.11 (0.47\u0026ndash;2.62)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.81\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eNot applicable\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eDrop in hemoglobin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e450\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e879\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.12 (-0.06-0.31)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.18\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.88\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.08\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e201\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1017\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.16 (-0.10-0.42)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.22\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel and aspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e34\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e619\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.00 (-0.58-0.58)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.00\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eNot applicable\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNumber of patients receiving blood transfusion\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e253/450\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e465/879\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.16 (0.91\u0026ndash;1.46)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.23\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.39\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.03\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e118/361\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e875/2965\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.19 (0.90\u0026ndash;1.59)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.23\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e36\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel and aspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e24/34\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e337/619\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e2.01 (0.94\u0026ndash;4.27)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.07\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eNot applicable\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMean number of units of blood transfused\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e530\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1185\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.13 (-0.13-0.40)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.32\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e49\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.23\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.07\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e7\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e250\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2487\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.15 (-0.25-0.56)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.46\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e71\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel and aspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e49\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e641\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.69 (0.10\u0026ndash;1.28)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.02\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eLength of hospital stay\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e380\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e808\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e-0.39 (-0.83-0.06)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.09\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.03\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.76\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e257\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1203\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.58 (-0.17-1.34)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.13\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel and aspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e49\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e641\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.97 (-0.40-2.34)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.17\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eReoperation\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3/223\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e3/304\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.35 (0.28\u0026ndash;6.61)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.71\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.93\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.29\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e10/216\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e33/1037\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.47 (0.70\u0026ndash;3.09)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.31\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAcute coronary syndrome\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e8/118\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e5/137\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.92 (0.61\u0026ndash;6.04)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.26\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eNot applicable\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.52\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.004\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e14/240\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e19/984\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e2.27 (1.07\u0026ndash;4.81)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.03\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel and aspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3/15\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0/22\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e12.60 (0.60-264.14)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eNot applicable\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCerebrovascular events\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2/140\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1/159\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.64 (0.27\u0026ndash;9.79)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.59\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e39\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.76\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.53\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2/84\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e4/249\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.77 (0.35\u0026ndash;9.04)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.49\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel and aspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0/15\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1/22\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.46 (0.02\u0026ndash;12.12)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.64\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eNot applicable\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eDeep venous thrombosis\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e9/476\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e11/923\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.50 (0.58\u0026ndash;3.84)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.40\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e61\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.94\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.30\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2/162\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e14/1435\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.60 (0.45\u0026ndash;5.74)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.47\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel and aspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0/34\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e9/619\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.93 (0.05\u0026ndash;16.33)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.96\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eNot applicable\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePulmonary embolism\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2/358\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e4/786\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.06 (0.22\u0026ndash;5.14)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.95\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.79\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.54\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2/251\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e14/1664\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.37 (0.44\u0026ndash;4.23)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.59\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel and aspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0/34\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2/619\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e3.58 (0.17\u0026ndash;76.02)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.41\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eNot applicable\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWound-related complications\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e14/498\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e25/945\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.86 (0.44\u0026ndash;1.69)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.67\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.34\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.48\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e8\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e14/287\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e35/2398\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.52 (0.75\u0026ndash;3.09)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.24\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel and aspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2/49\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e10/641\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e2.60 (0.49\u0026ndash;13.74)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.26\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMajor bleeding\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAspirin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3/98\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e10/342\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.05 (0.28\u0026ndash;3.89)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.94\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eNot applicable\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.58\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.48\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eClopidogrel\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e5/91\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e13/444\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.75 (0.52\u0026ndash;5.91)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.37\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe found that antiplatelet therapy was significantly associated with an increase in the number of transfused patients (OR\u0026thinsp;=\u0026thinsp;1.21; 95% CI, 1.01\u0026ndash;1.44; p\u0026thinsp;=\u0026thinsp;0.03). No evidence of statistical heterogeneity or publication bias was detected. Although the analysis of the three subgroups showed no differences in the transfusion rate, we focused on the overall results rather than on a separate subgroup because a test for interaction yielded a p value of 0.39.\u003c/p\u003e \u003cp\u003eThere were no significant differences in the decline in haemoglobin or mean number of units of blood transfused between the two groups despite the increase in the transfusion rate. Moderate statistical heterogeneity (p\u0026thinsp;=\u0026thinsp;0.002; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;61%) was observed for the mean number of units for transfusion, and a random-effect model was applied. Subgroup analysis showed that the combination of aspirin and clopidogrel may result in an increase in the mean number of units for transfusion (WMD\u0026thinsp;=\u0026thinsp;0.69; 95% CI, 0.10\u0026ndash;1.28; p\u0026thinsp;=\u0026thinsp;0.02). Sensitivity analysis was performed by excluding Zehir et al.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], which was the primary source of statistical heterogeneity. This may be because in this study, the preoperative haemoglobin levels of the antiplatelet group were significantly lower than that of the control group. Following removal of this study, a remarkable decrease in heterogeneity (p\u0026thinsp;=\u0026thinsp;0.08; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;37%) was observed and the overall results remained unchanged.\u003c/p\u003e \u003cp\u003eThere was also no significant difference in the length of hospital stay, reoperation, cerebrovascular events, deep vein thrombosis, pulmonary embolism, major bleeding, or other wound-related complications between the antiplatelet and non-antiplatelet groups, except for acute coronary syndrome (OR\u0026thinsp;=\u0026thinsp;2.41; 95% CI, 1.32\u0026ndash;4.42; p\u0026thinsp;=\u0026thinsp;0.004). Subgroup analysis suggested that the results did not change due to treatment with aspirin, clopidogrel or a combination of aspirin and clopidogrel. None of them showed significant heterogeneity or publication bias.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eWhich is better, early or delayed surgery on hip fracture patients with antiplatelet therapy?\u003c/h2\u003e \u003cp\u003eA total of 9 studies were included to compare early surgery (\u0026lt;\u0026thinsp;5 days) with delayed surgery (\u0026gt;\u0026thinsp;5 days) for hip fracture patients treated with antiplatelet therapy upon admission. There was a significant decrease in mortality (OR\u0026thinsp;=\u0026thinsp;0.43; 95% CI, 0.23\u0026ndash;0.79; p\u0026thinsp;=\u0026thinsp;0.006) for those treated with antiplatelet therapy with early surgery (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). No evidence of statistical heterogeneity or publication bias was observed. Sensitivity analysis did not change the overall results. Subgroup analysis revealed that the point estimate regarding the association of delayed surgery and mortality at any time point was increased, but only 3-month mortality reached statistical significance.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eEarly surgery was significantly associated with increased haemoglobin loss in hip fracture patients who received antiplatelet drugs (WMD\u0026thinsp;=\u0026thinsp;0.75; 95% CI, 0.50-1.00; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). However, there were no significant differences in the number of blood transfusions (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) or mean number of units for transfusion (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). There was remarkable statistical heterogeneity (p\u0026thinsp;=\u0026thinsp;0.01; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;72%) and possible publication bias for the mean number of units for transfusion. Sensitivity analysis was performed by separately excluding Zehir et al[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and the results remained unchanged.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe length of hospital stay in the early surgery group was significantly shortened (WMD = -6.05; 95% CI, -7.06-5.04; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). Nevertheless, there were no significant differences for acute coronary syndrome, cerebrovascular events, deep vein thrombosis, pulmonary embolism, major bleeding or other wound-related complications (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). Moreover, no heterogeneity was observed, and the results were not altered by separately excluding subgroups after sensitivity analysis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e "},{"header":"Discussion","content":" \u003cp\u003eHip fracture patients tend to be older, with a high mortality rate, and their quality of life is seriously affected.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] As the global elderly population is gradually increasing, the number of elderly patients with hip fractures and the socioeconomic burden are also increasing year by year.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] Most of them usually suffer from cardio-cerebrovascular disease and need antiplatelet therapy. Some believe that it is necessary to withhold antiplatelet therapy to promote platelet function recovery and reduce the risk of perioperative bleeding. Others believe that surgery should be performed as soon as possible without stopping medication. Previous literature has found that there is an absence of a consensus or policies for the treatment of patients who sustain hip fractures while on antiplatelet therapy. A telephone questionnaire data analysis about current practical measures among 110 orthopaedics in the UK showed that 56.4% of orthopaedics did not have a standard of clopidogrel withdrawal, and the remaining 43.6% stopped clopidogrel before surgery. Among them, 20.9% of the surgeries were delayed by more than 5 days, and 12.7% were delayed by 7\u0026ndash;10\u0026nbsp;days.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAlthough Soo et al.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] and Doleman et al.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] tried to identify how to manage these cases, the total numbers of studies included in these reviews were low, and these studies may result in type II errors and were either limited to one specific antiplatelet drug or confused the presence or absence of antiplatelet drugs with early or delayed surgery. Thus, we performed a more systematic and specific search and analysis to address the issues highlighted from previous research. The important finding of our study is that early surgery for hip fracture patients taking antiplatelet drugs might promote a higher risk of bleeding and more blood transfusion requirements compared to those without antiplatelet therapy. Nevertheless, there were no significant differences in prognosis. Instead, delayed intervention will lead to higher mortality and a longer hospital stay.\u003c/p\u003e \u003cp\u003eThere were several limitations to our study. One of the limitations was that the methodological quality of the studies included was not optimal. Only observational studies were included in our analysis, which means that only the inference of association is possible rather than causality; there may be potential confounding variables that bias the outcomes. For instance, there were three main types of hip fracture surgery in included studies: hip repair using internal fixation, partial hip replacement surgery, and total hip replacement surgery. Different surgical methods will affect the outcomes, but most of the included studies did not distinguish and explain so that we were unable to exclude this confounding factor. As expected, the intervention groups in most studies[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22 CR23 CR24 CR25\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] showed a significant increase in the number of cardiovascular or cerebrovascular comorbidities; however, surprisingly, only three of them showed a significant difference in the ASA grade.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] Moreover, the preoperative haemoglobin values of the intervention group in five studies[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] were significantly lower than those of the control group, which may potentially influence blood transfusions, meaning that the intervention groups required more units of blood. This may be why Zehir et al.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] was the main source of heterogeneity in the outcomes for the mean number of units for transfusion. A further limitation was that publication bias existed in some studies as shown in the funnel plots; this might because the number of included trials was less than 10. Finally, although we performed subgroup analysis based on the types of antiplatelet drugs and data were used from patients on one specific drug and not on the others simultaneously as much as possible, most of the trials included patients concurrently treated with aspirin in the clopidogrel subgroup, and this may affect the final results.\u003c/p\u003e \u003cp\u003eRegarding whether early surgery is safe for hip fracture patients taking antiplatelet drugs, the number of patients transfused in the antiplatelet group increased statistically, which was consistent with that in cardiac surgery.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] However, we found no convincing evidence of an increase in the average blood transfusion demands, except for in the medicine-united group. This suggested that there might indeed be an increased risk of bleeding in intraoperative blood loss or hidden blood loss, especially when antiplatelet drugs are used in combination.[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] However, because of the concerns of antiplatelets from anaesthesiologists and physicians, the patients taking antiplatelet drugs are more likely to have a lower threshold to receive transfusions. No differences in mortality, duration of hospital stay, reoperation rate or related complications, except acute coronary syndrome, was detected between the two groups. The presence of more vascular comorbidities in the antiplatelet group of most studies may be responsible for the significant increase in acute coronary syndrome.\u003c/p\u003e \u003cp\u003eRegarding whether early or delayed surgery is better for patients with hip fractures on antiplatelet therapy, early surgery was associated with a greater decrease in haemoglobin; however, there were no differences in the transfusion rate or mean number of units for transfusion. This also supports the fact that patients taking antiplatelet drugs are more likely to be transfused owing to potential performance bias. Multiple studies have shown that delays in surgery for more than 2 days for hip fracture patients are closely related to an increased risk of complications due to long-term bedridden and delayed mobilization.[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] Early surgical intervention can significantly reduce postoperative mortality and morbidity, promote a shorter hospital stay, and prompt patients to return to pre\u0026shy;injury ambulation status.[\u003cspan additionalcitationids=\"CR35 CR36 CR37\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] However, early surgery for patients on antiplatelet may cause haemorrhagic accidents, as platelet function has not fully recovered[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] In our study, delayed surgery increased the risk of mortality, and subgroup analysis showed that the point estimate regarding mortality at any time point was increased, especially mortality at 30 days and 3 months, which showed significant differences. Furthermore, hip fractures are more likely to prolong the length of hospital stay than any other musculoskeletal injuries, accounting for more than two-thirds of all hospital stays caused by fractures.[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e] Early surgery can effectively shorten the length of hospital stay and reduce social and economic burdens. Unlike previous research studies, our study suggests that there are no differences in the incidence of postoperative complications between early and delayed surgery. Previous studies have demonstrated that sudden withdrawal will lead to conversion to a prothrombotic and proinflammatory condition, which may complicate surgery and lead to adverse clinical events, such as recurrence and death by myocardial infarction, which has already been stabilized by drugs or stents.[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] However, in the meta-analysis reported here, subgroup analysis showed that a surgical delay did not have a higher postoperative incidence of cardiocerebrovascular events or thromboembolic events, and early surgery did not result in a higher incidence of severe bleeding.\u003c/p\u003e "},{"header":"Conclusion","content":" \u003cp\u003eIn conclusion, our analysis of 24 trials including a total of 5423 patients suggests that early surgery can be safely performed on hip fracture patients receiving antiplatelet drugs upon admission. Current evidence shows that although early surgery carries a high risk of bleeding, it does not lead to substantial blood transfusion demands or haemorrhagic events. Furthermore, compared with delayed surgery, early surgical intervention is associated with a significant decrease in mortality (p\u0026thinsp;=\u0026thinsp;0.006) and length of hospital stay (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Based on the available evidence, it is unnecessary to delay surgery to restore platelet function when patients with hip fractures receive antiplatelet therapy. Early surgery can significantly reduce mortality and hospital stay, which is conducive to patient recovery. Further large-scale, multi-centred, well-motivated and well-designed randomized trials are required to confirm these findings and develop clearer guidelines for the treatment of these patients.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eAbbreviations\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePRISMA: Preferred Reporting Items for Systematic Review and Meta-Analysis statement; NOS: Newcastle/Ottawa scale; SDs: Standard deviations; ORs: Odds ratios; WMDs: Weighted mean differences; CIs: Confidence intervals.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis article does not contain any studies with human participants or animals performed by any of the authors.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in published articles.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors' contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eJDN and ZYY contributed to the conception and design of the study. ZYY performed the statistical analysis and drafted the manuscript. ZL and LTK contributed to the literature search and study selection. LTK and YQG contributed to the quality assessment. YQG and SBT contributed to the data extraction. SBT contributed to the revisions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the authors of the included studies for their help.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMorris AH, Zuckerman JD. National Consensus Conference on Improving the Continuum of Care for Patients with Hip Fracture. \u003cem\u003eJ Bone Joint Surg Am \u003c/em\u003e2002;84-a(4):670-674.\u003c/li\u003e\n\u003cli\u003eKoval KJ, Zuckerman JD. Hip Fractures: I. 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Analysis of 102 hemiarthroplasties. \u003cem\u003eJournal of orthopaedics and traumatology : official journal of the Italian Society of Orthopaedics and Traumatology \u003c/em\u003e2013;14(3):171-177.\u003c/li\u003e\n\u003cli\u003eManaqibwala MI, Butler KA, Sagebien CA. Complications of hip fracture surgery on patients receiving clopidogrel therapy. \u003cem\u003eArchives of Orthopaedic and Trauma Surgery \u003c/em\u003e2014;134(6):747-753.\u003c/li\u003e\n\u003cli\u003eNydick JA, Farrell ED, Marcantonio AJ, Hume EL, Marburger R, Ostrum RF. The Use of Clopidogrel (Plavix) in Patients Undergoing Nonelective Orthopaedic Surgery. \u003cem\u003eJournal of Orthopaedic Trauma \u003c/em\u003e2010;24(6):383-386.\u003c/li\u003e\n\u003cli\u003eWallace HC, Probe RA, Chaput CD, Patel KV. Operative treatment of hip fractures in patients on clopidogrel: a case-control study. \u003cem\u003eThe Iowa orthopaedic journal \u003c/em\u003e2012;32:95-99.\u003c/li\u003e\n\u003cli\u003eWordsworth DR, Halsey T, Griffiths R, Parker MJ. Clopidogrel has no effect on mortality from hip fracture. \u003cem\u003eInjury-International Journal of the Care of the Injured \u003c/em\u003e2013;44(6):743-746.\u003c/li\u003e\n\u003c/ol\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-orthopaedic-surgery-and-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"josr","sideBox":"Learn more about [Journal of Orthopaedic Surgery and Research](http://josr-online.biomedcentral.com)","snPcode":"13018","submissionUrl":"https://submission.nature.com/new-submission/13018/3","title":"Journal of Orthopaedic Surgery and Research","twitterHandle":"@MSKmedBMC","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Hip fractures, meta-analysis, platelet aggregation inhibitors, aspirin","lastPublishedDoi":"10.21203/rs.2.23034/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.23034/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Background: Hip fractures are common and account for a large proportion of orthopaedic surgical admissions in elderly patients. However, determining the timing for surgery has been controversial for patients who develop with hip fractures while on antiplatelet treatment.\nMethods: Computerized databases for studies published from the inception date to January 2020, including the Cochrane Library, PubMed (Medline), EMBASE, Web of Science TM , ClinicalTrials, ClinicalKey and Google Scholar, were searched using the keywords “Hip AND Fracture”, “Antiplatelet”, “Antithrombocyte”, “Platelet aggregation inhibitors”, “Aspirin”, “Plavix”, and “Clopidogrel”.\nResults: In total, 2328 initial articles were identified. Twenty-four studies with 5423 participants were ultimately included in our analysis. Early surgery was associated with an increased transfusion rate in the antiplatelet group compared to the non-antiplatelet group (OR = 1.21; 95% CI, 1.01 to 1.44; p = 0.03). Early surgery for hip fracture patients on antiplatelet therapy was associated with a greater decrease in haemoglobin compared to delayed surgery (WMD = 0.75; 95% CI, 0.50 to 1.00; p \u003c 0.001). However, early surgery appeared to decrease the length of hospitalization (WMD = -6.05; 95% CI, -7.06 to -5.04; p \u003c 0.001) and mortality (OR = 0.43; 95% CI, 0.23 to 0.79; p = 0.006).\nConclusion: It is unnecessary to delay surgery to restore platelet function when patients with hip fractures receive antiplatelet therapy. Furthermore, early surgery can significantly reduce mortality and hospital stay, which is conducive to patient recovery. Future randomized trials should determine whether the results are sustained over time.","manuscriptTitle":"Is hip fracture surgery safe for patients on antiplatelet drugs and is it necessary to delay surgery? A Systematic Review and Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-02-11 05:51:04","doi":"10.21203/rs.2.23034/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2020-03-03T12:00:00+00:00","index":2,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"decision","content":"Accept","date":"2020-03-03T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-02-20T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-02-18T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-02-18T12:00:00+00:00","index":1,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"reviewersInvited","content":"","date":"2020-02-08T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-02-07T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-02-07T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-02-06T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-02-05T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-orthopaedic-surgery-and-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"josr","sideBox":"Learn more about [Journal of Orthopaedic Surgery and Research](http://josr-online.biomedcentral.com)","snPcode":"13018","submissionUrl":"https://submission.nature.com/new-submission/13018/3","title":"Journal of Orthopaedic Surgery and Research","twitterHandle":"@MSKmedBMC","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5717266d-c4e1-430d-a6e3-5f613c9f0b25","owner":[],"postedDate":"February 11th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":57154,"name":"Orthopedics"},{"id":57155,"name":"Orthopedic Surgery"}],"tags":[],"updatedAt":"2021-09-27T18:29:29+00:00","versionOfRecord":{"articleIdentity":"rs-13604","link":"https://doi.org/10.1186/s13018-020-01624-7","journal":{"identity":"journal-of-orthopaedic-surgery-and-research","isVorOnly":false,"title":"Journal of Orthopaedic Surgery and Research"},"publishedOn":"2020-03-12 18:24:54","publishedOnDateReadable":"March 12th, 2020"},"versionCreatedAt":"2020-02-11 05:51:04","video":"","vorDoi":"10.1186/s13018-020-01624-7","vorDoiUrl":"https://doi.org/10.1186/s13018-020-01624-7","workflowStages":[]},"version":"v1","identity":"rs-13604","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-13604","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}