Ticagrelor Versus Clopidogrel in The Treatment of Elderly Chinese Chronic Total Occlusion Patients Undergoing PCI

Ticagrelor Versus Clopidogrel in The Treatment of Elderly Chinese Chronic Total Occlusion Patients Undergoing PCI | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Ticagrelor Versus Clopidogrel in The Treatment of Elderly Chinese Chronic Total Occlusion Patients Undergoing PCI Peng Han, Ying Liang, Suining Xu, Shuai Zhao, Yan Chen, Ziwei Wang, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1195001/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Taking thrombosis and bleeding risks into consideration, little real world study data is available to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in elderly Chinese chronic total occlusion (CTO) patients. Methods: We assigned 504 CTO patients aged ≥75 years who successfully underwent PCI from December 2009 to May 2020. The patients were randomized to Clopidogrel and Ticagrelor group and received DAPT for up to 12 months. Efficacy endpoints were evaluated by major adverse cardiac events (MACE) consisting of all-cause death, nonfatal myocardial infarction (MI) and clinically driven revascularization. The safety endpoints were recorded as the incidence of Bleeding Academic Research Consortium (BARC) bleeding. Results: Patients in Clopidogrel group were older, they had a higher percentage of BMI, diastolic blood pressure and HDL-C than those in Ticagrelor group. Clopidogrel group had a lower percentage of hyperlipidemia, prior PCI, glucose, TG and LDL-C. No significant difference was found as to the Angiographic and procedural characteristics (P＞0.05 for all). After 12 months' follow-up, the incidence of MACE (12.19% vs. 11.04%, P=0.763) and bleeding (9.38% vs. 13.64%, P=0.205) had no significant difference. After clinical characteristics balanced matching by IPTWs model, we found that Ticagrelor had an unfavorable effect on reducing the incidence of bleeding with the IPTWs model (IPTW-OR, 1.81, 95% CI: 1.18-2.76, P=0.006). Conclusions: This clinical study demonstrated that Clopidogrel should be recommended to elderly CTO patients after PCI, especially those with a high bleeding risk. Trial registration: The study protocol was approved by the Ethics Committee of Air Force Medical University (KY20172019-1). Cardiac & Cardiovascular Systems Ticagrelor Clopidogrel aged percutaneous coronary intervention chronic total occlusion Figures Figure 1 Figure 2 Figure 3 Background Coronary CTO is observed in approximatively 15-25% of CAD patients have undergone prior coronary angiography [ 1 , 2 ] . Guidelines recommend selective PCI to CTO patients to improve their symptoms and quality of life, and patients who undergo successful CTO-PCI have higher survival rates [ 3 , 4 ] . As CTO lesions are complex and intraoperative stent placement is frequent, the risk of thrombosis is high; therefore, intensive DAPT is recommended for CTO-PCI patients to prevent stent thrombosis [ 5 , 6 ] . However, continuous antiplatelet therapy is also associated with increased bleeding risk, leading to the necessity to balance the risk of bleeding and ischemia. As the elderly population over 75 years has a much higher risk of bleeding, more concern is needed for the adjustment of DAPT medication to elderly CTO-PCI patients. Consequently, it is of great significance to investigate the efficacy and safety of different DAPT strategies for elderly CTO-PCI patients. However, traditional clinical randomized controlled trials seldom focused on elderly CTO patients, and data on Chinese elderly CTO patients after PCI is scarcely available. In addition, most CTO-PCI DAPT studies focused on duration rather than medication selection, which makes current clinical studies of Chinese elderly CTO-PCI patients’ DAPT medication selection underrepresented. Ticagrelor and Clopidogrel are two of the most commonly used DAPT drugs. Compared with Clopidogrel, Ticagrelor has faster action, stronger antiplatelet effect and its effect is reversible [ 7 ] . A study on Chinese CTO-PCI patients investigated the efficacy and safety of Ticagrelor and Clopidogrel, in which there were three groups (Ticagrelor group of 90 mg twice daily, Ticagrelor group of 60 mg twice daily, and Clopidogrel group of 75 mg once daily). The major adverse cardiac and cerebral events (MACCE, all-cause mortality, target vessel revascularization, stent thrombosis, nonfatal MI, and nonfatal stroke), major bleeding and minor bleeding incidence were separately 7.3% vs. 6.4% vs. 14.2%, ( P =0.023), 4.1% vs. 0.6% vs. 0.6%, ( P =0.016) and 23.4% vs. 12.4% vs. 11.9%, ( P =0.004) [ 8 ] . These results indicate that Ticagrelor with normal dose has lower incidence of MACE but higher bleeding incidence compared with Clopidogrel in Chinese CTO-PCI patients. However, the study did not reveal information on elderly patients, and there is no study related to elderly CTO patients’ DAPT. Therefore, it of necessity to investigate elderly CTO-PCI patients. Herein, the current study is designed to assess the efficacy and safety of Ticagrelor in comparison with Clopidogrel on a background of Aspirin for elderly Chinese CTO patients who have undergone prior PCI. Methods Study design This study was conducted in the department of cardiology, Xijing Hospital from December 2009 to May 2020 to compare the efficacy and safety of Ticagrelor versus Clopidogrel in elderly Chinese CTO patients who previously underwent elective PCI with drug-eluting stents (DES). PCI success was assessed by the interventional cardiologist performing the procedure. The study protocol was approved by the Ethics Committee of Air Force Medical University (KY20172019-1). Written informed consents were obtained from all participants. Study participants From December 2009 to May 2020, a total of 504 CTO patients who successfully underwent elective PCI followed by DAPT for up to 12 months were consecutively enrolled in the study and randomized to treatment with Ticagrelor or Clopidogrel. Of the 504 patients, 30 were lost to follow-up, and eventually 474 patients were included in this study. For these participants, 320 of them took 100mg Aspirin and Clopidogrel with a 300mg loading dose followed by a dose of 75 mg daily, while the other 154 patients took 100mg Aspirin and Ticagrelor with a loading dose of 180 mg followed by a dose of 90 mg twice daily. All the patients took Aspirin at a dose of 100 mg daily. CTO was defined as angiographic evidence of total occlusion with complete interruption of anterograde blood flow (Thrombolysis In Myocardial Infarction (TIMI) flow grade 0) with an estimated duration of>3 months via previous angiograms, angina symptoms and a history of MI [ 2 ] . Coronary arteries measured were proximal left main artery (LM), left anterior descending artery (LAD), right coronary artery (RCA) and left circumflex artery (LCX). Inclusion criteria included: 1) age ≥75 years old; 2) confirmed with CTO by coronary angiography; 3) successful PCI; 4) informed consent signed by the patient. Exclusion criteria included: 1) conservative oral anticoagulation therapy; 2) PCI contraindications; 3) P2Y12 inhibitors contraindications; 4) high risk of bleeding diathesis or coagulation disorder; 5) dialysis-dependent renal failure or liver cirrhosis; 6) refusal to participate in this study by the patient. Clinical, angiographic and procedural baseline data were collected and recorded. Study end points Clinical follow-up was carried out by telephone interviews and outpatient visits. The follow-up period started from the date of DAPT use after PCI and ended when any study outcome first occurred or at 12 months after PCI. Inpatient observation and outpatient visits were scheduled for patients being regularly followed up in our hospital, while telephone calls were made for patients without regular medical follow-up. The incidence of end points was collected in medical records by a predefined questionnaire, in which health status, physical examinations, vital signs as well as laboratory assessments were simultaneously recorded. The efficacy endpoints in this study were evaluated by the occurrence of MACE, i.e., the composite of all-cause death, nonfatal MI and clinically driven revascularization. All-cause death was defined as death from any cause, which was ascertained without adjudication [ 9 ] . MI was defined as the presence of recurrent cardiac ischemic symptoms, new Q waves in ≥ 2 contiguous electrocardiographic leads or an elevation of creatine kinase (CK) level or its MB isoenzyme (CK-MB) to at least 3 times the upper limit of normal in 2 plasma samples [ 10 ] . Clinically driven revascularization was defined as any reintervention because of symptoms [ 11 ] . The safety endpoints were evaluated by the incidence of bleeding: Bleeding Academic Research Consortium (BARC) type 1, 2, 3, or 5 [ 12 ] . Type 1 is inactive bleeding. Type 2 is active bleeding requiring evaluation or intervention by medical personnel, which differs from Type 3, Type 5 and bleeding related to coronary artery bypass graft. Type 3 is heavy bleeding as well as intracranial bleeding with significant hemoglobin reduction to 5g/dl, which requires blood transfusion. For Type 5, it refers to potential or qualitative fatal bleeding. The major bleeding events, which are the equivalent of BARC 3 and 5, include gastrointestinal bleeding, intracranial hemorrhage, hemoglobin decrease of ≥3 g/dL, significant bleeding requiring blood transfusion, and fatal bleeding [ 13 ] . Statistical analysis Continuous variable was described as mean ± SD or median and interquartile spacing, and categorical variable as number (percentage). Differences in continuous and categorical variables between groups were analyzed with Mann–Whitney U-test and Chi-square test respectively, and P < 0.05 was considered to be statistically significant. Univariate logistic regression models were developed to explore the effect of treatment. To validate the effects of treatment groups on the incidence of bleeding, a propensity score weighting method was adopted according to the results of univariate factor comparison and literature reports. A logistic model was used to calculate propensity score, in which the dependent variable was Ticagrelor group and the covariates included age, DBP, hyperlipidemia, prior PCI, GLU, TG, LDL-C and HDL-C. Standardized mean differences (SMD) (< 0.20 is indicative of good balance) were calculated to evaluate the balance of the inverse probability of treatment weighting (IPTW) model. Finally, the IPTW odds ratio (IPTW-OR) was derived for Ticagrelor group. Results Clinical, angiographic and procedural baseline characteristics In this study, a total of 504 CTO patients (≥75 years) were prescribed with DAPT for 12 months after PCI from December 2009 to May 2020. During this period of time (12 months after PCI), 30 patients were lost to follow-up, and in the end 474 CTO patients were included in the study (Figure 1 ). In terms of clinical baseline characteristics, compared with the patients in Ticagrelor group, those in Clopidogrel group were older (80.45±4.23 vs. 79.18±3.59, P =0.001) and had a higher percentage of BMI (24.14±3.49 vs. 22.82±4.75, P =0.003), more elevated diastolic blood pressure (74.53±10.16 vs. 71.82±9.85, P =0.007) and higher HDL-C (1.92±0.87 vs. 1.05±0.29, P <0.001). A lower percentage of patients in Clopidogrel group had hyperlipidemia (22.50% vs. 43.51%, P <0.001) and prior PCI (25.63% vs. 39.61%, P =0.003), and they had lower glucose (24.14±3.49 vs. 22.82±4.75, P =0.003), TG (1.31±0.78 vs. 1.48±0.85, P =0.037) and LDL-C (1.22±0.71 vs. 1.96±0.75, P 0.05 for all) (Table 1 ). For CTO lesion characteristics, no significant differences were found as to the CTO lesions of coronary arteries (LM, LAD, RCA, and LCX), number of treated vessels, number of stents or total stent length ( P >0.05 for all) (Table 2 ). Table 1 Baseline clinical characteristics (n=474) Variable Clopidogrel (n=320) Ticagrelor (n=154) P value Age, years 80.45±4.23 79.18±3.59 0.001 Male, % 230 (71.88) 115 (74.68) 0.582 BMI 24.14±3.49 22.82±4.75 0.003 Heart rate, beats/min 73.15±12.33 72.24±10.74 0.437 SBP, mmHg 130.02±22.71 128.39±25.38 0.487 DBP, mmHg 74.53±10.16 71.82±9.85 0.007 Smoking, % 87 (27.19) 33 (21.43) 0.215 Medical history Hypertension, % 192 (60.00) 85 (55.19) 0.322 Diabetes mellitus, % 90 (28.13) 48 (31.17) 0.518 Hyperlipidemia 72(22.50) 67 (43.51) <0.001 Valvular heart disease, % 2 (0.63) 0 1.000 Atrial fibrillation, % 12 (375) 4 (2.60) 0.598 Stroke, % 33 (10.31) 19 (12.34) 0.532 Chronic kidney diseases, % 8 (2.50) 8 (5.19) 0.172 Peripheral arterial disease, % 2 (0.63) 0 1.000 Family history of CAD, % 0 2 (1.30) 0.105 Prior MI, % 15 (4.69) 10 (6.49) 0.511 Prior PCI, % 82 (25.63) 61 (39.61) 0.003 Prior CABG, % 8 (2.50) 2 (1.30) 0. 511 Laboratory data WBC (10 9 /L) 6.65±2.19 6.87±3.79 0.420 RBC (10 12 /L) 4.24±0.61 4.24±0.53 0.946 Hb (g/L) 131.19±18.45 129.87±17.01 0.457 PLT (10 9 /L) 177.32±67.05 189.04±60.24 0.066 Creatinine (µmol/L) 108.20±52.01 114.93±82.86 0.288 Ccr (ml/min) 49.09±13.88 46.40±13.54 0.104 BUN (mmol/L) 5.89±2.20 6.06±1.97 0.655 UA (µmol/L) 311.00±289.95 313.27±89.20 0.930 ALT (U/L) 20.00 (16.75) 21.00 (11.00) 0.578 AST (U/L) 20.00 (13.00) 16.00 (12.85) 0.177 Alb (g/L) 38.49±4.99 37.96±3.94 0.363 Glu (mmol/L) 6.19±2.42 6.97±3.04 0.007 TC (mmol/L) 3.64±1.07 3.52±0.89 0.236 TG (mmol/L) 1.31±0.78 1.48±0.85 0.037 LDL-C(mmol/L) 1.22±0.71 1.96±0.75 <0.001 HDL-C(mmol/L) 1.92±0.87 1.05±0.29 <0.001 NT-proBNP (pg/ml) 598.30 (1415.98) 661.50 (2065.50) 0.229 LVEF (%) 52.17±9.36 51.12±9.29 0.303 Abbreviations: CAD, coronary artery disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; BMI, Body Mass Index; SBP, systolic blood pressure; DBP, diastolic blood pressure; WBC, white blood cell; RBC, red blood cell; Hb, Hemoglobin; PLT, blood platelet ; Ccr, creatinine clearance; BUN, blood urea nitrogen; UA, uric acid; ALT, alanine amiotransferase; AST, aspartate aminotransferase; Alb, albumin; Glu, Glucose; TC, triglyceride; TG, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction. Table 2 Angiographic and procedural characteristics Variable Clopidogrel (n=320) Ticagrelor (n=154) P value CTO Lesion characteristics, % LM 2 (0.63) 0 1.000 RCA 149 (46.56) 76 (49.35) 0.624 LAD 158 (49.38) 71 (46.10) 0.556 LCX 96 (30.00) 53 (34.42) 0.343 Number of treated CTO vessels, % 1 308 (96.25) 144 (93.51) 0.242 2 12 (3.75) 9 (5.84) 0.342 3 0 1 (0.65) 0.325 Number of stents 2.42±1.16 2.40±1.15 0.842 Total stent length, mm 61.13±34.18 61.36±36.55 0.948 Abbreviations: CTO, chronic total occlusion; LM, left main; LAD, left anterior descending; RCA, right coronary artery; LCX, left circumflex. Clinical outcomes on follow-up After 12 months’ follow-up, the incidence of MACE was 12.19% in Clopidogrel group and 11.04% in Ticagrelor group, with no statistical significance ( P >0.05). The individual components in the two groups were not significantly different either, which included all-cause death (10.94% vs. 11.04%), nonfatal MI (0.31% vs. 1.30%) and clinically driven revascularization (0.94% vs. 0). The total bleeding rate (9.38% vs. 13.64%) and BARC 1 bleeding (8.13% vs. 12.99%) of Clopidogrel group were lower than those of Ticagrelor group, but with no statistical significance ( P >0.05) (Table 3 ). Considering that the factors that might be related to bleeding were not balanced, the IPTW model was used to balance the clinical characteristics from the two groups (Figure 2 ). The characteristics were significantly balanced after matching, and it was found that compared with Clopidogrel, Ticagrelor had an adverse impact on the reduction of the incidence of bleeding with the IPTW model (IPTW-OR: 1.81, 95% CI: 1.18-2.76, P =0.006) (Figure 3 ). Table 3 Efficacy and safety points Variable Clopidogrel (n=320) Ticagrelor (n=154) P value MACE, % 39 (12.19) 17 (11.04) 0.763 All-cause death, % 35 (10.94) 17 (11.04) 1.000 Nonfatal myocardial infarction, % 1 (0.31) 2 (1.30) 0.248 Clinically driven revascularization, % 3 (0.94) 0 0.554 Bleeding, % 30 (9.38) 21 (13.64) 0.205 BARC 1, % 26 (8.13) 20 (12.99) 0.100 BARC 2, % 2 (0.63) 0 1.000 BARC 3, % 0 0 BARC 5, % 2 (0.63) 1 (0.65) 1.000 Discussion PCI is feasible for CTO with high success rates [ 14 ] , but CTO-PCI patients have higher ischemic risk because of more complex lesions. Therefore, prolonged DAPT duration is recommended for these patients [ 2 , 5 ] . Elderly CTO-PCI patients are also at high risk of bleeding [ 15 ] , which makes it vitally important to balance the risks of both thrombose and hemorrhage for CTO-PCI patients to ensure a desirable prognosis. Previous studies indicated that the improvement of clinical outcomes was irrespective of whether the duration of DAPT after PCI in CTO patients was >12 months or not [ 16 , 17 ] . Considering the reasons above, the duration of DAPT in this study was determined as 12 months. DAPT, which comprises aspirin and a P2Y12 inhibitor, prevents both stent thrombosis and non-culprit segments thrombosis via antiplatelet aggregation to reduce coronary ischemic events after PCI. As P2Y12 inhibitors recommended by many guidelines, Ticagrelor and Clopidogrel can prevent adenosine diphosphate (ADP) dependent activation of platelet aggregation by binding to the P2Y12 receptor [ 5 , 6 ] . According to the results of the PLATO trial, compared with Clopidogrel, Ticagrelor showed a lower incidence of endpoint events including cardiovascular death, MI and stroke (9.8% vs. 11.7%, P <0.001) without increasing bleeding risk (11.6% vs. 11.2%, P= 0.43) [ 18 , 19 ] . In the ESTATE study that enrolled Taiwan acute coronary syndrome (ACS) patients, compared with patients taking Clopidogrel, those who took Ticagrelor had a lower incidence of MI, stroke, or vascular death endpoints with marginal statistical significance (7.1% vs. 11.6%, P= 0.07), and the incidence of all bleeding was similar (19.6% vs. 14.3%, P= 0.13) [ 20 ] . Among these studies, more than 80% patients received invasive therapies (PCI or coronary artery bypass grafting (CABG)). The PLATO trial contained 587 Chinese patients (3.1%) and also 2878 elderly patients (15.45%) [ 18 , 19 ] , and the ESTATE study included 269 (28.99%) Chinese patients older than 75 years [ 20 ] . In these studies data concerning CTO patients was absent, and Chinese elderly patients accounted only for a small number of the subjects enrolled in the studies. Consequently, these studies could hardly be representative of Chinese elderly CTO patients. In the present study, all the patients were aged ≥75 years and underwent PCI with DES. After 12-month DAPT, the incidence of MACE in Ticagrelor group was lower than that in Clopidogrel group (11.04% vs. 12.19%), but the incidences of overall bleeding (13.64% vs. 9.38%) and BARC 1 bleeding (12.99% vs. 8.13%) were higher in Ticagrelor group, with no statistical significance for all the differences. After balancing clinical characteristics of the two groups, the difference of bleeding incidence was found to be statistically significant. This indicates that Ticagrelor has similar effect in reducing MACE but higher bleeding risk for Chinese elderly CTO-PCI patients. Thus, Ticagrelor showed similar efficiency but worse safety in comparison with Clopidogrel in our study. Several studies showed that Clopidogrel had similar MACE but higher bleeding incidence than Ticagrelor for patients after PCI [ 21 – 23 ] . There is a “East Asian paradox” which describes that East Asian patients have lower ischemic but higher bleeding risk after PCI [ 24 ] . In the PHILO trial which targeted mostly Japanese patients, compared with Clopidogrel, Ticagrelor was associated with higher incidence of overall bleeding events (23.8% vs. 14.7%, hazard ratio (HR): 1.72; 95% CI: 1.23-2.40) and minor bleeding events (15.2% vs. 9.2%, HR: 1.75; 95% CI: 1.15-2.67), and the incidence of ischemic events (the composite of MI, stroke or vascular-cause death) is not significantly different (9.0% vs. 6.3%, HR: 1.47; 95% CI: 0.88-2.44) [ 25 ] . The TICAKOREA trial indicated that in comparison with Clopidogrel group, Ticagrelor group had higher incidence of clinically significant bleeding (11.7% vs. 5.3%, P= 0.002) and minor bleeding (5.2% vs. 1.3%, P =0.02), and the incidence of cardiovascular death, MI and stroke was not significantly different between the two groups (9.2% vs. 5.8%, P= 0.07) [ 26 ] . The Kamir-NIH study based on East Asian population showed that Ticagrelor reduced the risk of ischemic event with statistical significance (8.6% vs. 11.9%, P= 0.018), but it had a significantly higher bleeding risk than Clopidogrel (10.8% vs. 4.8%, P <0.001) for patients with acute myocardial infarction (AMI) and multivessel disease (MVD) [ 27 ] . These studies support the perception that East Asian patients with the medication of Ticagrelor have a higher incidence of bleeding complications, especially minor bleeding, which is consistent with our findings. There are few studies aiming at DATP for Chinese CTO patients or elderly patients who underwent PCI, let alone post- PCI patients with CTO who aged ≥75 years in China. In a study on Chinese CTO patients who underwent PCI, the incidences of overall MACE, major bleeding and minor bleeding in normal Ticagrelor dose group and Clopidogrel group were (7.3% vs. 14.2%), (4.1% vs. 0.6%) and (23.4% vs. 11.9%), respectively [ 8 ] . This indicates that normal dose Ticagrelor renders lower incidence of MACE but higher bleeding incidence compared with Clopidogrel for Chinese CTO patients. According to the POPular AGE study involving 1002 patients (aged ≥70 years) with non-ST-elevation acute coronary syndrome (NSTE-ACS), the primary bleeding outcome incidence was higher in Ticagrelor group (24% vs. 18%, P =0.02), and there were no significant differences as to the incidence of cardiovascular death, MI, and stroke between the two groups (11% vs. 12%, P =0.71) [ 28 ] , which is in favor of the conclusion that Clopidogrel is recommended for elderly NSTE-ACS patients with a high bleeding risk. The MACE incidence in the POPular AGE study is similar to that in our study, whereas in other studies the MACE incidence of Ticagrelor group is lower than that in our study. This might be attributed to the greater complexity of lesions of elderly CTO patients, which leads to higher MACE risks. The bleeding incidence in Ticagrelor group in our study is higher than those in the TICAKOREA trial and Kamir-NIH study but is lower than incidences in other studies. This may be partly due to the research bias brought by small sample size as well as the differences of baseline and procedure characteristics between the groups that might affect the comparison of the endpoints. It is found that DAPT after PCI can benefit elderly CTO-PCI patients, and Ticagrelor showed similar MACE and higher incidence of bleeding, especially minor bleeding (BARC 1 bleeding) compared with Clopidogrel; therefore, we believe Clopidogrel has similar efficiency and better safety for elderly Chinese CTO-PCI patients. As Ticagrelor has higher bleeding incidence, it should be prescribed with caution to patients with a high bleeding risk. This study may make potential contribution to clinical practice, but it is essential to carry out a further prospective, multi-center and large-scale study to compare the efficacy and safety outcomes of Ticagrelor and Clopidogrel in elderly Chinese CTO patients who underwent PCI. Study limitations There are several limitations in the current study. Firstly, it was a single center study with a small sample size, in which the selection bias was hardly avoidable. Secondly, we did not distinguish cardiovascular death in our follow-up, and we did not assess CTO score, opening techniques or the occurrence of stroke. Thirdly, owing to the unavailability of the information on the date of nonfatal MI and clinically driven revascularization, we did not adjust the analysis of efficacy end points accordingly. Fourthly, we did not include other related therapeutic agents such as β-blocker and other drugs, and we did not evaluate the major adverse effects of P2Y12 inhibitors including dyspnea, hyperuricemia, and asymptomatic heart block. Conclusions This clinical study demonstrated that in the improvement of elderly Chinese CTO patients’ prognosis, Clopidogrel is found to be more desirable for elderly Chinese CTO patients after PCI because of lower incidence of bleeding events. Consequently, Clopidogrel should be recommended for elderly CTO patients after PCI, especially patients with a high bleeding risk. Abbreviations DAPT: dual antiplatelet therapy; PCI: percutaneous coronary intervention; CTO: chronic total occlusion; MACE: major adverse cardiac event; MI: myocardial infarction; BARC: Bleeding Academic Research Consortium; DES: drug-eluting stents; TIMI: Thrombolysis In Myocardial Infarction; LM: left main artery；LAD: left anterior descending artery; RCA: right coronary artery; LCX: left circumflex artery; CK: creatine kinase; CK-MB: creatine kinase MB isoenzyme; SMD: standardized mean differences; IPTW: inverse probability of treatment weighting; ADP: adenosine diphosphate; ACS: acute coronary syndrome; CABG: coronary artery bypass grafting; AMI: acute myocardial infarction; MVD: multivessel disease; NSTE-ACS: non-ST-elevation acute coronary syndrome. Declarations Ethics approval and consent to participate The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Air Force Medical University (KY20172019-1). Written informed consents were obtained from all participants. Consent for publication The consent was obtained from all authors for publication of this study. Availability of data and materials The datasets generated and analysed during the current study are available from the corresponding author on reasonable request. Funding This work was supported by Shaanxi province Key Research and Development Program General Project- Social Development (2018SF-153), Xi’an Science and Technology Project (20YXYJ0003(4)), New Clinical Technology and New Business of Xijing Hospital (XJGX15Y39), Bethune-Merck Diabetes Research Foundation (G2017044). Conflict of interest statement The authors have no conflicts of interest to declare. Authors' contributions Peng Han contributed to the original draft writing and editing of the work; Suining Xu contributed to the design and editing; Ying Liang and Zhijun Tan contributed to the statistical analyses; Shuai Zhao, Yan Chen, Ziwei Wang, Yuhao Chen, Boda Zhu, Zhilin Sha and Anxin Shen contributed to the data curation; Feng Tao contributed to the language editing; Qin Wang, Qiong Wang, Genrui Chen, Li Yang and Haokao Gao contributed to the review and editing; Kun Lian and Chengxiang Li contributed to the project administration and supervision. All authors read and approved the final manuscript. Acknowledgements The authors are grateful to Qing Yan, Jianan Wu and Jin Li for their help with the collection of data in this study. Authors’ information Peng Han, Ying Liang, and Suining Xu contributed equally to this work. Corresponding author: Kun Lian Department of Cardiology, Xijing Hospital, Airforce Military Medical University, 169 West Changle Road, Xi'an, Shaanxi 710032, P.R. China Telephone: 0086-17792398286 E-mail: [email protected] . Co-corresponding author: Chengxiang Li Department of Cardiology, Xijing Hospital, Airforce Military Medical University, 169 West Changle Road, Xi'an, Shaanxi 710032, P.R. China Telephone: 0086-13992816228 E-mail: [email protected] Author details 1 Department of Cardiology, 981 Hospital of Joint Logistics Support Force, Chengde, Hebei 067000, P. R. China. 2 Department of Cardiology, Xijing Hospital, Airforce Military Medical University, Xi'an, Shaanxi 710032, P. R. China. 3 Department of Health Statistics, Airforce Military Medical University, Xi'an, Shaanxi 710032, P. R. China. 4 Department of Cardiology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shannxi 710077, P. R. China. 5 Department of Cardiology, No.971 Hospital of the PLA Navy, Qingdao, Shandong 266071, P. R. China. 6 Cadet Brigade, School of Basic Medicine, Airforce Military Medical University, Xi'an, Shannxi 710032, P.R. China. 7 Department of Naval Medicine, Naval Medical University, Shanghai 200433, P. R. China 8 Department of Pharmacogenomics, Airforce Military Medical University, Xi'an, Shaanxi 710032, P. R. China. 9 Department of Cardiology, Hanyin County People's Hospital, Ankang, Shaanxi 725100, P. R. China References Fefer P, Knudtson ML, Cheema AN, et al. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter Chronic Total Occlusions Registry. J Am Coll Cardiol. 2012;59(11):991–997. Galassi AR, Werner GS, Boukhris M, et al. Percutaneous recanalisation of chronic total occlusions: 2019 consensus document from the EuroCTO Club. EuroIntervention. 2019;15(2):198–208. 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Science Bulletin. 2019; 64: 166–179. 2012 Writing Committee Members, Jneid H, Anderson JL, et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/Non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation, 2012. 126(7): 875–910. Wang Y, Zhao HW, Wang CF, et al. Efficacy and safety of standard and low dose Ticagrelor versus Clopidogrel in east Asian Patients with chronic total occlusion undergoing percutaneous coronary intervention: a single center retrospective study. BMC Cardiovasc Disord. 2020;20(1):109. Hicks KA, Mahaffey KW, Mehran R, et al. 2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials. J Am Coll Cardiol, 2018. 71(9): 1021–1034. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction guidelines. Eur Heart J 2018; 40: 237–69. Scheinert D, Micari A, Brodmann M, et al. Drug-Coated Balloon Treatment for Femoropopliteal Artery Disease. Circ Cardiovasc Interv, 2018. 11(10): e005654. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation, 2011. 123(23): 2736–47. Choi JH, Seo JM, Lee DH, Park K, Kim YD. Clinical utility of new bleeding criteria: a prospective study of evaluation for the Bleeding Academic Research Consortium definition of bleeding in patients undergoing percutaneous coronary intervention. J Cardiol. 2015;65(4):324–329. Lee SW, Lee PH, Ahn JM, et al. Randomized Trial Evaluating Percutaneous Coronary Intervention for the Treatment of Chronic Total Occlusion. Circulation. 2019;139(14):1674–1683. Costa F, Van Klaveren D, Feres F, et al. Dual Antiplatelet Therapy Duration Based on Ischemic and Bleeding Risks After Coronary Stenting. J Am Coll Cardiol. 2019;73(7):741–754. Sachdeva A, Hung YY, Solomon MD, McNulty EJ. Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention for Chronic Total Occlusion. Am J Cardiol. 2020;132:44–51. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Thorac Cardiovasc Surg, 2016. 152(5): 1243–1275. Husted S, James S, Becker RC, et al. Ticagrelor versus Clopidogrel in elderly patients with acute coronary syndromes: a substudy from the prospective randomized PLATelet inhibition and patient Outcomes (PLATO) trial. Circ Cardiovasc Qual Outcomes, 2012. 5(5): 680–8. Kang HJ, Clare RM, Gao R, et al. Ticagrelor versus Clopidogrel in Asian patients with acute coronary syndrome: A retrospective analysis from the Platelet Inhibition and Patient Outcomes (PLATO) Trial. Am Heart J, 2015. 169(6): 899-905.e1. Chen IC, Lee CH, Fang CC, et al. Efficacy and safety of Ticagrelor versus Clopidogrel in acute coronary syndrome in Taiwan: A multicenter retrospective pilot study. J Chin Med Assoc, 2016. 79(10): 521–30. Silvain J, Lattuca B, Beygui F, et al. Ticagrelor versus Clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial. Lancet. 2020;396(10264):1737–1744. You SC, Rho Y, Bikdeli B, et al. Association of Ticagrelor vs Clopidogrel With Net Adverse Clinical Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. JAMA. 2020;324(16):1640–1650. Turgeon RD, Koshman SL, Youngson E, et al. Association of Ticagrelor vs Clopidogrel with Major Adverse Coronary Events in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. JAMA Intern Med. 2020;180(3):420–428. Kang J, Kim HS. The Evolving Concept of Dual Antiplatelet Therapy after Percutaneous Coronary Intervention: Focus on Unique Feature of East Asian and "Asian Paradox". Korean Circ J. 2018;48(7):537–551. Goto S, Huang CH, Park SJ, Emanuelsson H, Kimura T. Ticagrelor vs. clopidogrel in Japanese, Korean and Taiwanese patients with acute coronary syndrome -- randomized, double-blind, phase III PHILO study. Circ J. 2015;79(11):2452–2460. Park DW, Kwon O, Jang JS, et al. Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management: A Randomized Clinical Trial. Circulation. 2019;140(23):1865–1877. Ahn JH, Ahn Y, Jeong MH, et al. Ticagrelor versus Clopidogrel in acute myocardial infarction patients with multivessel disease; From Korea Acute Myocardial Infarction Registry-National Institute of Health. J Cardiol. 2020;75(5):478–484. Gimbel M, Qaderdan K, Willemsen L, et al. Clopidogrel versus Ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial. Lancet. 2020;395(10233):1374–1381. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1195001","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":74662559,"identity":"549a0793-5005-4b65-a5e7-1a09d06d990a","order_by":0,"name":"Peng Han","email":"","orcid":"","institution":"981 Hospital of Joint Logistics Support Force","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"Han","suffix":""},{"id":74662562,"identity":"ab4c64c5-c2b6-4c97-9c3d-2e2d8bd01fbf","order_by":1,"name":"Ying Liang","email":"","orcid":"","institution":"Airforce Military Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Liang","suffix":""},{"id":74662563,"identity":"7cda13c8-4913-40c8-a4d9-2100668eba8f","order_by":2,"name":"Suining Xu","email":"","orcid":"","institution":"The First Affiliated Hospital of Xi'an Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Suining","middleName":"","lastName":"Xu","suffix":""},{"id":74662565,"identity":"aaeb778d-c719-4f67-b617-f3f75cbe6ec7","order_by":3,"name":"Shuai Zhao","email":"","orcid":"","institution":"Xijing Hospital, Airforce Military Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shuai","middleName":"","lastName":"Zhao","suffix":""},{"id":74662567,"identity":"e880d9f8-d1b5-4ae6-90d4-bb939565a3a1","order_by":4,"name":"Yan Chen","email":"","orcid":"","institution":"971 Hospital of the PLA 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Airforce Military Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Kun","middleName":"","lastName":"Lian","suffix":""}],"badges":[],"createdAt":"2021-12-22 08:59:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1195001/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1195001/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":17115035,"identity":"a28b3bb1-a838-4fc4-b4d0-84785806ac9f","added_by":"auto","created_at":"2022-01-07 20:29:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":80387,"visible":true,"origin":"","legend":"\u003cp\u003eStudy workflow\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1195001/v1/8c8af4a6f121cd56da2a0093.png"},{"id":17114798,"identity":"81e6b824-d55f-45c8-978a-7ae0da5e9c1d","added_by":"auto","created_at":"2022-01-07 20:26:58","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":243845,"visible":true,"origin":"","legend":"\u003cp\u003eStandardized mean differences weighted and unweighted propensity score matching for the corresponding variable\u0026nbsp;\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1195001/v1/bd0d2f9c4a57c59c9ca30d9f.png"},{"id":17115036,"identity":"b68d5c7f-8445-46c0-815b-0be981587ddf","added_by":"auto","created_at":"2022-01-07 20:29:58","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":941317,"visible":true,"origin":"","legend":"\u003cp\u003eUnvariate analysis and IPTWs estimate of ticagrelor (vs. clopidogrel) on the occurrence of bleeding\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-1195001/v1/0fbe032efcf7039754ddb28b.png"},{"id":18292756,"identity":"6e2fd3ce-98be-4e73-b633-2f6c4e07965c","added_by":"auto","created_at":"2022-02-16 17:29:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":787994,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1195001/v1/c6916b89-e882-49a7-9d51-a1464d781261.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eTicagrelor Versus Clopidogrel in The Treatment of Elderly Chinese Chronic Total Occlusion Patients Undergoing PCI\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eCoronary CTO is observed in approximatively 15-25% of CAD patients have undergone prior coronary angiography \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Guidelines recommend selective PCI to CTO patients to improve their symptoms and quality of life, and patients who undergo successful CTO-PCI have higher survival rates \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. As CTO lesions are complex and intraoperative stent placement is frequent, the risk of thrombosis is high; therefore, intensive DAPT is recommended for CTO-PCI patients to prevent stent thrombosis \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. However, continuous antiplatelet therapy is also associated with increased bleeding risk, leading to the necessity to balance the risk of bleeding and ischemia. As the elderly population over 75 years has a much higher risk of bleeding, more concern is needed for the adjustment of DAPT medication to elderly CTO-PCI patients. Consequently, it is of great significance to investigate the efficacy and safety of different DAPT strategies for elderly CTO-PCI patients. However, traditional clinical randomized controlled trials seldom focused on elderly CTO patients, and data on Chinese elderly CTO patients after PCI is scarcely available. In addition, most CTO-PCI DAPT studies focused on duration rather than medication selection, which makes current clinical studies of Chinese elderly CTO-PCI patients\u0026rsquo; DAPT medication selection underrepresented.\u003c/p\u003e \u003cp\u003eTicagrelor and Clopidogrel are two of the most commonly used DAPT drugs. Compared with Clopidogrel, Ticagrelor has faster action, stronger antiplatelet effect and its effect is reversible \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. A study on Chinese CTO-PCI patients investigated the efficacy and safety of Ticagrelor and Clopidogrel, in which there were three groups (Ticagrelor group of 90 mg twice daily, Ticagrelor group of 60 mg twice daily, and Clopidogrel group of 75 mg once daily). The major adverse cardiac and cerebral events (MACCE, all-cause mortality, target vessel revascularization, stent thrombosis, nonfatal MI, and nonfatal stroke), major bleeding and minor bleeding incidence were separately 7.3% vs. 6.4% vs. 14.2%, (\u003cem\u003eP\u003c/em\u003e=0.023), 4.1% vs. 0.6% vs. 0.6%, (\u003cem\u003eP\u003c/em\u003e=0.016) and 23.4% vs. 12.4% vs. 11.9%, (\u003cem\u003eP\u003c/em\u003e=0.004) \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. These results indicate that Ticagrelor with normal dose has lower incidence of MACE but higher bleeding incidence compared with Clopidogrel in Chinese CTO-PCI patients. However, the study did not reveal information on elderly patients, and there is no study related to elderly CTO patients\u0026rsquo; DAPT. Therefore, it of necessity to investigate elderly CTO-PCI patients.\u003c/p\u003e \u003cp\u003eHerein, the current study is designed to assess the efficacy and safety of Ticagrelor in comparison with Clopidogrel on a background of Aspirin for elderly Chinese CTO patients who have undergone prior PCI.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis study was conducted in the department of cardiology, Xijing Hospital from December 2009 to May 2020 to compare the efficacy and safety of Ticagrelor versus Clopidogrel in elderly Chinese CTO patients who previously underwent elective PCI with drug-eluting stents (DES). PCI success was assessed by the interventional cardiologist performing the procedure. The study protocol was approved by the Ethics Committee of Air Force Medical University (KY20172019-1). Written informed consents were obtained from all participants.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy participants\u003c/h2\u003e \u003cp\u003eFrom December 2009 to May 2020, a total of 504 CTO patients who successfully underwent elective PCI followed by DAPT for up to 12 months were consecutively enrolled in the study and randomized to treatment with Ticagrelor or Clopidogrel. Of the 504 patients, 30 were lost to follow-up, and eventually 474 patients were included in this study. For these participants, 320 of them took 100mg Aspirin and Clopidogrel with a 300mg loading dose followed by a dose of 75 mg daily, while the other 154 patients took 100mg Aspirin and Ticagrelor with a loading dose of 180 mg followed by a dose of 90 mg twice daily. All the patients took Aspirin at a dose of 100 mg daily. CTO was defined as angiographic evidence of total occlusion with complete interruption of anterograde blood flow (Thrombolysis In Myocardial Infarction (TIMI) flow grade 0) with an estimated duration of\u003e3 months via previous angiograms, angina symptoms and a history of MI\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Coronary arteries measured were proximal left main artery (LM), left anterior descending artery (LAD), right coronary artery (RCA) and left circumflex artery (LCX). Inclusion criteria included: 1) age \u0026ge;75 years old; 2) confirmed with CTO by coronary angiography; 3) successful PCI; 4) informed consent signed by the patient. Exclusion criteria included: 1) conservative oral anticoagulation therapy; 2) PCI contraindications; 3) P2Y12 inhibitors contraindications; 4) high risk of bleeding diathesis or coagulation disorder; 5) dialysis-dependent renal failure or liver cirrhosis; 6) refusal to participate in this study by the patient. Clinical, angiographic and procedural baseline data were collected and recorded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStudy end points\u003c/h2\u003e \u003cp\u003eClinical follow-up was carried out by telephone interviews and outpatient visits. The follow-up period started from the date of DAPT use after PCI and ended when any study outcome first occurred or at 12 months after PCI. Inpatient observation and outpatient visits were scheduled for patients being regularly followed up in our hospital, while telephone calls were made for patients without regular medical follow-up. The incidence of end points was collected in medical records by a predefined questionnaire, in which health status, physical examinations, vital signs as well as laboratory assessments were simultaneously recorded. The efficacy endpoints in this study were evaluated by the occurrence of MACE, i.e., the composite of all-cause death, nonfatal MI and clinically driven revascularization. All-cause death was defined as death from any cause, which was ascertained without adjudication \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. MI was defined as the presence of recurrent cardiac ischemic symptoms, new Q waves in \u0026ge; 2 contiguous electrocardiographic leads or an elevation of creatine kinase (CK) level or its MB isoenzyme (CK-MB) to at least 3 times the upper limit of normal in 2 plasma samples \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Clinically driven revascularization was defined as any reintervention because of symptoms \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. The safety endpoints were evaluated by the incidence of bleeding: Bleeding Academic Research Consortium (BARC) type 1, 2, 3, or 5\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Type 1 is inactive bleeding. Type 2 is active bleeding requiring evaluation or intervention by medical personnel, which differs from Type 3, Type 5 and bleeding related to coronary artery bypass graft. Type 3 is heavy bleeding as well as intracranial bleeding with significant hemoglobin reduction to 5g/dl, which requires blood transfusion. For Type 5, it refers to potential or qualitative fatal bleeding. The major bleeding events, which are the equivalent of BARC 3 and 5, include gastrointestinal bleeding, intracranial hemorrhage, hemoglobin decrease of \u0026ge;3 g/dL, significant bleeding requiring blood transfusion, and fatal bleeding\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e .\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variable was described as mean \u0026plusmn; SD or median and interquartile spacing, and categorical variable as number (percentage). Differences in continuous and categorical variables between groups were analyzed with Mann\u0026ndash;Whitney U-test and Chi-square test respectively, and \u003cem\u003eP\u003c/em\u003e\u0026lt; 0.05 was considered to be statistically significant. Univariate logistic regression models were developed to explore the effect of treatment. To validate the effects of treatment groups on the incidence of bleeding, a propensity score weighting method was adopted according to the results of univariate factor comparison and literature reports. A logistic model was used to calculate propensity score, in which the dependent variable was Ticagrelor group and the covariates included age, DBP, hyperlipidemia, prior PCI, GLU, TG, LDL-C and HDL-C. Standardized mean differences (SMD) (\u0026lt; 0.20 is indicative of good balance) were calculated to evaluate the balance of the inverse probability of treatment weighting (IPTW) model. Finally, the IPTW odds ratio (IPTW-OR) was derived for Ticagrelor group.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv class=\"Section2\" id=\"Sec8\"\u003e\n \u003ch2\u003eClinical, angiographic and procedural baseline characteristics\u003c/h2\u003e\n \u003cp\u003eIn this study, a total of 504 CTO patients (\u0026ge;75 years) were prescribed with DAPT for 12 months after PCI from December 2009 to May 2020. During this period of time (12 months after PCI), 30 patients were lost to follow-up, and in the end 474 CTO patients were included in the study (Figure \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). In terms of clinical baseline characteristics, compared with the patients in Ticagrelor group, those in Clopidogrel group were older (80.45\u0026plusmn;4.23 vs. 79.18\u0026plusmn;3.59, \u003cem\u003eP\u003c/em\u003e=0.001) and had a higher percentage of BMI (24.14\u0026plusmn;3.49 vs. 22.82\u0026plusmn;4.75, \u003cem\u003eP\u003c/em\u003e=0.003), more elevated diastolic blood pressure (74.53\u0026plusmn;10.16 vs. 71.82\u0026plusmn;9.85, \u003cem\u003eP\u003c/em\u003e=0.007) and higher HDL-C (1.92\u0026plusmn;0.87 vs. 1.05\u0026plusmn;0.29, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001). A lower percentage of patients in Clopidogrel group had hyperlipidemia (22.50% vs. 43.51%, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001) and prior PCI (25.63% vs. 39.61%, \u003cem\u003eP\u003c/em\u003e=0.003), and they had lower glucose (24.14\u0026plusmn;3.49 vs. 22.82\u0026plusmn;4.75, \u003cem\u003eP\u003c/em\u003e=0.003), TG (1.31\u0026plusmn;0.78 vs. 1.48\u0026plusmn;0.85, \u003cem\u003eP\u003c/em\u003e=0.037) and LDL-C (1.22\u0026plusmn;0.71 vs. 1.96\u0026plusmn;0.75, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001). There were no significant differences among the other clinical characteristics (\u003cem\u003eP\u003c/em\u003e\u003e0.05 for all) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). For CTO lesion characteristics, no significant differences were found as to the CTO lesions of coronary arteries (LM, LAD, RCA, and LCX), number of treated vessels, number of stents or total stent length (\u003cem\u003eP\u003c/em\u003e\u003e0.05 for all) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline clinical characteristics (n=474)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eClopidogrel (n=320)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTicagrelor (n=154)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.45\u0026plusmn;4.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e79.18\u0026plusmn;3.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e230 (71.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e115 (74.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.582\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.14\u0026plusmn;3.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.82\u0026plusmn;4.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeart rate, beats/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.15\u0026plusmn;12.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.24\u0026plusmn;10.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.437\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSBP, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e130.02\u0026plusmn;22.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e128.39\u0026plusmn;25.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.487\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDBP, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.53\u0026plusmn;10.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.82\u0026plusmn;9.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87 (27.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33 (21.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.215\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedical history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e192 (60.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85 (55.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.322\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90 (28.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48 (31.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.518\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHyperlipidemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72(22.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67 (43.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eValvular heart disease, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAtrial fibrillation, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (375)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (2.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.598\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStroke, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33 (10.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (12.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.532\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic kidney diseases, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (2.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (5.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.172\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeripheral arterial disease, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFamily history\u0026nbsp;of\u0026nbsp;CAD, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.105\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrior MI, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (4.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (6.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.511\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrior PCI, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82 (25.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61 (39.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrior CABG, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (2.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0. 511\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLaboratory data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWBC (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.65\u0026plusmn;2.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.87\u0026plusmn;3.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.420\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRBC (10\u003csup\u003e12\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.24\u0026plusmn;0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.24\u0026plusmn;0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.946\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHb (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e131.19\u0026plusmn;18.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e129.87\u0026plusmn;17.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.457\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePLT (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e177.32\u0026plusmn;67.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e189.04\u0026plusmn;60.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.066\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCreatinine (\u0026micro;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e108.20\u0026plusmn;52.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e114.93\u0026plusmn;82.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.288\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCcr (ml/min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.09\u0026plusmn;13.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.40\u0026plusmn;13.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBUN (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.89\u0026plusmn;2.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.06\u0026plusmn;1.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.655\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUA (\u0026micro;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e311.00\u0026plusmn;289.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e313.27\u0026plusmn;89.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.930\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eALT (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.00 (16.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.00 (11.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.578\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAST (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.00 (13.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.00 (12.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.177\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlb (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.49\u0026plusmn;4.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.96\u0026plusmn;3.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.363\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGlu (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.19\u0026plusmn;2.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.97\u0026plusmn;3.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTC (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.64\u0026plusmn;1.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.52\u0026plusmn;0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.236\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTG (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.31\u0026plusmn;0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.48\u0026plusmn;0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.037\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.22\u0026plusmn;0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.96\u0026plusmn;0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.92\u0026plusmn;0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.05\u0026plusmn;0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNT-proBNP (pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e598.30 (1415.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e661.50 (2065.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.229\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLVEF (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52.17\u0026plusmn;9.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51.12\u0026plusmn;9.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.303\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eAbbreviations: CAD, coronary artery disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; BMI, Body Mass Index; SBP, systolic blood pressure; DBP, diastolic blood pressure; WBC, white blood cell; RBC, red blood cell; Hb, Hemoglobin; PLT, blood platelet ; Ccr, creatinine clearance; BUN, blood urea nitrogen; UA, uric acid; ALT, alanine amiotransferase; AST, aspartate aminotransferase; Alb, albumin; Glu, Glucose; TC, triglyceride; TG, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAngiographic and procedural characteristics\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eClopidogrel (n=320)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTicagrelor (n=154)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCTO Lesion characteristics, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e149 (46.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76 (49.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.624\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158 (49.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71 (46.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.556\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLCX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96 (30.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53 (34.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.343\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of treated CTO vessels, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e308 (96.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e144 (93.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.242\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (3.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (5.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.342\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.325\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of stents\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.42\u0026plusmn;1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.40\u0026plusmn;1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.842\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal stent length, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61.13\u0026plusmn;34.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61.36\u0026plusmn;36.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.948\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eAbbreviations: CTO, chronic total occlusion; LM, left main; LAD, left anterior descending; RCA, right coronary artery; LCX, left circumflex.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec9\"\u003e\n \u003ch2\u003eClinical outcomes on follow-up\u003c/h2\u003e\n \u003cp\u003eAfter 12 months\u0026rsquo; follow-up, the incidence of MACE was 12.19% in Clopidogrel group and 11.04% in Ticagrelor group, with no statistical significance (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05). The individual components in the two groups were not significantly different either, which included all-cause death (10.94% vs. 11.04%), nonfatal MI (0.31% vs. 1.30%) and clinically driven revascularization (0.94% vs. 0). The total bleeding rate (9.38% vs. 13.64%) and BARC 1 bleeding (8.13% vs. 12.99%) of Clopidogrel group were lower than those of Ticagrelor group, but with no statistical significance (\u003cem\u003eP\u003c/em\u003e\u003e0.05) (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Considering that the factors that might be related to bleeding were not balanced, the IPTW model was used to balance the clinical characteristics from the two groups (Figure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The characteristics were significantly balanced after matching, and it was found that compared with Clopidogrel, Ticagrelor had an adverse impact on the reduction of the incidence of bleeding with the IPTW model (IPTW-OR: 1.81, 95% CI: 1.18-2.76, \u003cem\u003eP\u003c/em\u003e=0.006) (Figure \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eEfficacy and safety points\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eClopidogrel (n=320)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTicagrelor (n=154)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMACE, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39 (12.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (11.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.763\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAll-cause death, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35 (10.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (11.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNonfatal myocardial infarction, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.248\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eClinically driven revascularization, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (0.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.554\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBleeding, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30 (9.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (13.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.205\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBARC 1, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26 (8.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (12.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBARC 2, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBARC 3, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBARC 5, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePCI is feasible for CTO with high success rates\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e, but CTO-PCI patients have higher ischemic risk because of more complex lesions. Therefore, prolonged DAPT duration is recommended for these patients \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Elderly CTO-PCI patients are also at high risk of bleeding \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, which makes it vitally important to balance the risks of both thrombose and hemorrhage for CTO-PCI patients to ensure a desirable prognosis. Previous studies indicated that the improvement of clinical outcomes was irrespective of whether the duration of DAPT after PCI in CTO patients was \u0026gt;12 months or not \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. Considering the reasons above, the duration of DAPT in this study was determined as 12 months. DAPT, which comprises aspirin and a P2Y12 inhibitor, prevents both stent thrombosis and non-culprit segments thrombosis via antiplatelet aggregation to reduce coronary ischemic events after PCI. As P2Y12 inhibitors recommended by many guidelines, Ticagrelor and Clopidogrel can prevent adenosine diphosphate (ADP) dependent activation of platelet aggregation by binding to the P2Y12 receptor \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAccording to the results of the PLATO trial, compared with Clopidogrel, Ticagrelor showed a lower incidence of endpoint events including cardiovascular death, MI and stroke (9.8% vs. 11.7%, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001) without increasing bleeding risk (11.6% vs. 11.2%, \u003cem\u003eP=\u003c/em\u003e0.43) \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. In the ESTATE study that enrolled Taiwan acute coronary syndrome (ACS) patients, compared with patients taking Clopidogrel, those who took Ticagrelor had a lower incidence of MI, stroke, or vascular death endpoints with marginal statistical significance (7.1% vs. 11.6%, \u003cem\u003eP=\u003c/em\u003e0.07), and the incidence of all bleeding was similar (19.6% vs. 14.3%, \u003cem\u003eP=\u003c/em\u003e0.13) \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Among these studies, more than 80% patients received invasive therapies (PCI or coronary artery bypass grafting (CABG)). The PLATO trial contained 587 Chinese patients (3.1%) and also 2878 elderly patients (15.45%) \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e, and the ESTATE study included 269 (28.99%) Chinese patients older than 75 years \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. In these studies data concerning CTO patients was absent, and Chinese elderly patients accounted only for a small number of the subjects enrolled in the studies. Consequently, these studies could hardly be representative of Chinese elderly CTO patients.\u003c/p\u003e \u003cp\u003eIn the present study, all the patients were aged \u0026ge;75 years and underwent PCI with DES. After 12-month DAPT, the incidence of MACE in Ticagrelor group was lower than that in Clopidogrel group (11.04% vs. 12.19%), but the incidences of overall bleeding (13.64% vs. 9.38%) and BARC 1 bleeding (12.99% vs. 8.13%) were higher in Ticagrelor group, with no statistical significance for all the differences. After balancing clinical characteristics of the two groups, the difference of bleeding incidence was found to be statistically significant. This indicates that Ticagrelor has similar effect in reducing MACE but higher bleeding risk for Chinese elderly CTO-PCI patients. Thus, Ticagrelor showed similar efficiency but worse safety in comparison with Clopidogrel in our study.\u003c/p\u003e \u003cp\u003eSeveral studies showed that Clopidogrel had similar MACE but higher bleeding incidence than Ticagrelor for patients after PCI \u003csup\u003e[\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. There is a \u0026ldquo;East Asian paradox\u0026rdquo; which describes that East Asian patients have lower ischemic but higher bleeding risk after PCI \u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. In the PHILO trial which targeted mostly Japanese patients, compared with Clopidogrel, Ticagrelor was associated with higher incidence of overall bleeding events (23.8% vs. 14.7%, hazard ratio (HR): 1.72; 95% CI: 1.23-2.40) and minor bleeding events (15.2% vs. 9.2%, HR: 1.75; 95% CI: 1.15-2.67), and the incidence of ischemic events (the composite of MI, stroke or vascular-cause death) is not significantly different (9.0% vs. 6.3%, HR: 1.47; 95% CI: 0.88-2.44) \u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. The TICAKOREA trial indicated that in comparison with Clopidogrel group, Ticagrelor group had higher incidence of clinically significant bleeding (11.7% vs. 5.3%, \u003cem\u003eP=\u003c/em\u003e0.002) and minor bleeding (5.2% vs. 1.3%, \u003cem\u003eP\u003c/em\u003e=0.02), and the incidence of cardiovascular death, MI and stroke was not significantly different between the two groups (9.2% vs. 5.8%, \u003cem\u003eP=\u003c/em\u003e0.07) \u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. The Kamir-NIH study based on East Asian population showed that Ticagrelor reduced the risk of ischemic event with statistical significance (8.6% vs. 11.9%, \u003cem\u003eP=\u003c/em\u003e0.018), but it had a significantly higher bleeding risk than Clopidogrel (10.8% vs. 4.8%, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001) for patients with acute myocardial infarction (AMI) and multivessel disease (MVD) \u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. These studies support the perception that East Asian patients with the medication of Ticagrelor have a higher incidence of bleeding complications, especially minor bleeding, which is consistent with our findings.\u003c/p\u003e \u003cp\u003eThere are few studies aiming at DATP for Chinese CTO patients or elderly patients who underwent PCI, let alone post- PCI patients with CTO who aged \u0026ge;75 years in China. In a study on Chinese CTO patients who underwent PCI, the incidences of overall MACE, major bleeding and minor bleeding in normal Ticagrelor dose group and Clopidogrel group were (7.3% vs. 14.2%), (4.1% vs. 0.6%) and (23.4% vs. 11.9%), respectively \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. This indicates that normal dose Ticagrelor renders lower incidence of MACE but higher bleeding incidence compared with Clopidogrel for Chinese CTO patients. According to the POPular AGE study involving 1002 patients (aged \u0026ge;70 years) with non-ST-elevation acute coronary syndrome (NSTE-ACS), the primary bleeding outcome incidence was higher in Ticagrelor group (24% vs. 18%, \u003cem\u003eP\u003c/em\u003e=0.02), and there were no significant differences as to the incidence of cardiovascular death, MI, and stroke between the two groups (11% vs. 12%, \u003cem\u003eP\u003c/em\u003e=0.71) \u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e, which is in favor of the conclusion that Clopidogrel is recommended for elderly NSTE-ACS patients with a high bleeding risk.\u003c/p\u003e \u003cp\u003eThe MACE incidence in the POPular AGE study is similar to that in our study, whereas in other studies the MACE incidence of Ticagrelor group is lower than that in our study. This might be attributed to the greater complexity of lesions of elderly CTO patients, which leads to higher MACE risks. The bleeding incidence in Ticagrelor group in our study is higher than those in the TICAKOREA trial and Kamir-NIH study but is lower than incidences in other studies. This may be partly due to the research bias brought by small sample size as well as the differences of baseline and procedure characteristics between the groups that might affect the comparison of the endpoints.\u003c/p\u003e \u003cp\u003eIt is found that DAPT after PCI can benefit elderly CTO-PCI patients, and Ticagrelor showed similar MACE and higher incidence of bleeding, especially minor bleeding (BARC 1 bleeding) compared with Clopidogrel; therefore, we believe Clopidogrel has similar efficiency and better safety for elderly Chinese CTO-PCI patients. As Ticagrelor has higher bleeding incidence, it should be prescribed with caution to patients with a high bleeding risk. This study may make potential contribution to clinical practice, but it is essential to carry out a further prospective, multi-center and large-scale study to compare the efficacy and safety outcomes of Ticagrelor and Clopidogrel in elderly Chinese CTO patients who underwent PCI.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStudy limitations\u003c/h2\u003e \u003cp\u003eThere are several limitations in the current study. Firstly, it was a single center study with a small sample size, in which the selection bias was hardly avoidable. Secondly, we did not distinguish cardiovascular death in our follow-up, and we did not assess CTO score, opening techniques or the occurrence of stroke. Thirdly, owing to the unavailability of the information on the date of nonfatal MI and clinically driven revascularization, we did not adjust the analysis of efficacy end points accordingly. Fourthly, we did not include other related therapeutic agents such as β-blocker and other drugs, and we did not evaluate the major adverse effects of P2Y12 inhibitors including dyspnea, hyperuricemia, and asymptomatic heart block.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis clinical study demonstrated that in the improvement of elderly Chinese CTO patients\u0026rsquo; prognosis, Clopidogrel is found to be more desirable for elderly Chinese CTO patients after PCI because of lower incidence of bleeding events. Consequently, Clopidogrel should be recommended for elderly CTO patients after PCI, especially patients with a high bleeding risk.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eDAPT: dual antiplatelet therapy; PCI: percutaneous coronary intervention; CTO: chronic total occlusion; MACE: major adverse cardiac event; MI: myocardial infarction; BARC: Bleeding Academic Research Consortium; DES: drug-eluting stents; TIMI: Thrombolysis In Myocardial Infarction; LM: left main artery；LAD: left anterior descending artery; RCA: right coronary artery; LCX: left circumflex artery; CK: creatine kinase; CK-MB: creatine kinase MB isoenzyme; SMD: standardized mean differences; IPTW: inverse probability of treatment weighting; ADP: adenosine diphosphate; ACS: acute coronary syndrome; CABG: coronary artery bypass grafting; AMI: acute myocardial infarction; MVD: multivessel disease; NSTE-ACS: non-ST-elevation acute coronary syndrome.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Air Force Medical University (KY20172019-1). Written informed consents were obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe consent was obtained from all authors for publication of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Shaanxi province Key Research and Development Program General Project- Social Development (2018SF-153), Xi\u0026rsquo;an Science and Technology Project (20YXYJ0003(4)), New Clinical Technology and New Business of Xijing Hospital (XJGX15Y39), Bethune-Merck Diabetes Research Foundation (G2017044).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest statement \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePeng Han contributed to the original draft writing and editing of the work; Suining Xu contributed to the design and editing; Ying Liang and Zhijun Tan contributed to the statistical analyses; Shuai Zhao, Yan Chen, Ziwei Wang, Yuhao Chen, Boda Zhu, Zhilin Sha and Anxin Shen contributed to the data curation; Feng Tao contributed to the language editing; Qin Wang, Qiong Wang, Genrui Chen, Li Yang and Haokao Gao contributed to the review and editing; Kun Lian and Chengxiang Li contributed to the project administration and supervision. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are grateful to Qing Yan, Jianan Wu and Jin Li for their help with the collection of data in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePeng Han, Ying Liang, and Suining Xu contributed equally to this work.\u003c/p\u003e\n\u003cp\u003eCorresponding author:\u003c/p\u003e\n\u003cp\u003eKun Lian\u003c/p\u003e\n\u003cp\u003eDepartment of Cardiology, Xijing Hospital, Airforce Military Medical University, 169 West Changle Road, Xi\u0026apos;an, Shaanxi 710032, P.R. China\u003c/p\u003e\n\u003cp\u003eTelephone: 0086-17792398286\u003c/p\u003e\n\u003cp\u003eE-mail: [email protected].\u003c/p\u003e\n\u003cp\u003eCo-corresponding author:\u003c/p\u003e\n\u003cp\u003eChengxiang Li\u003c/p\u003e\n\u003cp\u003eDepartment of Cardiology, Xijing Hospital, Airforce Military Medical University, 169 West Changle Road, Xi\u0026apos;an, Shaanxi 710032, P.R. China\u003c/p\u003e\n\u003cp\u003eTelephone: 0086-13992816228\u003c/p\u003e\n\u003cp\u003eE-mail: [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Cardiology, 981 Hospital of Joint Logistics Support Force, Chengde, Hebei 067000, P. R. China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eDepartment of Cardiology, Xijing Hospital, Airforce Military Medical University, Xi\u0026apos;an, Shaanxi 710032, P. R. China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3\u003c/sup\u003eDepartment of Health Statistics, Airforce Military Medical University, Xi\u0026apos;an, Shaanxi 710032, P. R. China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e4\u003c/sup\u003eDepartment of Cardiology, The First Affiliated Hospital of Xi\u0026apos;an Medical University, Xi\u0026apos;an, Shannxi 710077, P. R. China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e5\u003c/sup\u003eDepartment of Cardiology, No.971 Hospital of the PLA Navy, Qingdao, Shandong 266071, P. R. China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e6\u003c/sup\u003eCadet Brigade, School of Basic Medicine, Airforce Military Medical University, Xi\u0026apos;an, Shannxi 710032, P.R. China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e7\u003c/sup\u003eDepartment of Naval Medicine, Naval Medical University, Shanghai 200433, P. R. China\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e8 \u003c/sup\u003eDepartment of Pharmacogenomics, Airforce Military Medical University, Xi\u0026apos;an, Shaanxi 710032, P. R. China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e9\u003c/sup\u003eDepartment of Cardiology, Hanyin County People\u0026apos;s Hospital, Ankang, Shaanxi 725100, P. R. China\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFefer P, Knudtson ML, Cheema AN, et al. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter Chronic Total Occlusions Registry. J Am Coll Cardiol. 2012;59(11):991\u0026ndash;997.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalassi AR, Werner GS, Boukhris M, et al. Percutaneous recanalisation of chronic total occlusions: 2019 consensus document from the EuroCTO Club. 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Circ Cardiovasc Interv, 2018. 11(10): e005654.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation, 2011. 123(23): 2736\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi JH, Seo JM, Lee DH, Park K, Kim YD. Clinical utility of new bleeding criteria: a prospective study of evaluation for the Bleeding Academic Research Consortium definition of bleeding in patients undergoing percutaneous coronary intervention. J Cardiol. 2015;65(4):324\u0026ndash;329.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee SW, Lee PH, Ahn JM, et al. Randomized Trial Evaluating Percutaneous Coronary Intervention for the Treatment of Chronic Total Occlusion. Circulation. 2019;139(14):1674\u0026ndash;1683.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCosta F, Van Klaveren D, Feres F, et al. Dual Antiplatelet Therapy Duration Based on Ischemic and Bleeding Risks After Coronary Stenting. J Am Coll Cardiol. 2019;73(7):741\u0026ndash;754.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSachdeva A, Hung YY, Solomon MD, McNulty EJ. Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention for Chronic Total Occlusion. Am J Cardiol. 2020;132:44\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLevine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Thorac Cardiovasc Surg, 2016. 152(5): 1243\u0026ndash;1275.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHusted S, James S, Becker RC, et al. Ticagrelor versus Clopidogrel in elderly patients with acute coronary syndromes: a substudy from the prospective randomized PLATelet inhibition and patient Outcomes (PLATO) trial. Circ Cardiovasc Qual Outcomes, 2012. 5(5): 680\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKang HJ, Clare RM, Gao R, et al. Ticagrelor versus Clopidogrel in Asian patients with acute coronary syndrome: A retrospective analysis from the Platelet Inhibition and Patient Outcomes (PLATO) Trial. Am Heart J, 2015. 169(6): 899-905.e1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen IC, Lee CH, Fang CC, et al. Efficacy and safety of Ticagrelor versus Clopidogrel in acute coronary syndrome in Taiwan: A multicenter retrospective pilot study. J Chin Med Assoc, 2016. 79(10): 521\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSilvain J, Lattuca B, Beygui F, et al. Ticagrelor versus Clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial. Lancet. 2020;396(10264):1737\u0026ndash;1744.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYou SC, Rho Y, Bikdeli B, et al. Association of Ticagrelor vs Clopidogrel With Net Adverse Clinical Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. JAMA. 2020;324(16):1640\u0026ndash;1650.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTurgeon RD, Koshman SL, Youngson E, et al. Association of Ticagrelor vs Clopidogrel with Major Adverse Coronary Events in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. JAMA Intern Med. 2020;180(3):420\u0026ndash;428.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKang J, Kim HS. The Evolving Concept of Dual Antiplatelet Therapy after Percutaneous Coronary Intervention: Focus on Unique Feature of East Asian and \"Asian Paradox\". Korean Circ J. 2018;48(7):537\u0026ndash;551.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoto S, Huang CH, Park SJ, Emanuelsson H, Kimura T. Ticagrelor vs. clopidogrel in Japanese, Korean and Taiwanese patients with acute coronary syndrome -- randomized, double-blind, phase III PHILO study. Circ J. 2015;79(11):2452\u0026ndash;2460.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark DW, Kwon O, Jang JS, et al. Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management: A Randomized Clinical Trial. Circulation. 2019;140(23):1865\u0026ndash;1877.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhn JH, Ahn Y, Jeong MH, et al. Ticagrelor versus Clopidogrel in acute myocardial infarction patients with multivessel disease; From Korea Acute Myocardial Infarction Registry-National Institute of Health. J Cardiol. 2020;75(5):478\u0026ndash;484.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGimbel M, Qaderdan K, Willemsen L, et al. Clopidogrel versus Ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial. Lancet. 2020;395(10233):1374\u0026ndash;1381.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ticagrelor, Clopidogrel, aged, percutaneous coronary intervention, chronic total occlusion","lastPublishedDoi":"10.21203/rs.3.rs-1195001/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1195001/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Taking thrombosis and bleeding risks into consideration, little real world study data is available to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in elderly Chinese chronic total occlusion (CTO) patients. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We assigned 504 CTO patients aged ≥75 years who successfully underwent PCI from December 2009 to May 2020. The patients were randomized to Clopidogrel and Ticagrelor group and received DAPT for up to 12 months. Efficacy endpoints were evaluated by major adverse cardiac events (MACE) consisting of all-cause death, nonfatal myocardial infarction (MI) and clinically driven revascularization. The safety endpoints were recorded as the incidence of Bleeding Academic Research Consortium (BARC) bleeding. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003ePatients in Clopidogrel group were older, they had a higher percentage of BMI, diastolic blood pressure and HDL-C than those in Ticagrelor group. Clopidogrel group had a lower percentage of hyperlipidemia, prior PCI, glucose, TG and LDL-C. No significant difference was found as to the Angiographic and procedural characteristics (P＞0.05 for all). After 12 months' follow-up, the incidence of MACE (12.19% vs. 11.04%, P=0.763) and bleeding (9.38% vs. 13.64%, P=0.205) had no significant difference. After clinical characteristics balanced matching by IPTWs model, we found that Ticagrelor had an unfavorable effect on reducing the incidence of bleeding with the IPTWs model (IPTW-OR, 1.81, 95% CI: 1.18-2.76, P=0.006). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e This clinical study demonstrated that Clopidogrel should be recommended to elderly CTO patients after PCI, especially those with a high bleeding risk. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTrial registration:\u003c/strong\u003e The study protocol was approved by the Ethics Committee of Air Force Medical University (KY20172019-1).\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Ticagrelor Versus Clopidogrel in The Treatment of Elderly Chinese Chronic Total Occlusion Patients Undergoing PCI","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-01-07 20:26:56","doi":"10.21203/rs.3.rs-1195001/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"12b6e3b0-bf3d-4f3b-a355-c8c763164db5","owner":[],"postedDate":"January 7th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":9601154,"name":"Cardiac \u0026 Cardiovascular Systems"}],"tags":[],"updatedAt":"2022-02-16T17:29:09+00:00","versionOfRecord":[],"versionCreatedAt":"2022-01-07 20:26:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1195001","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1195001","identity":"rs-1195001","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}