Clinical Features and Follow-up Outcomes of Individualized Low-dose DOAC Therapy in Chinese Patients Aged 60 Years and Older: A Single-center Study

Clinical Features and Follow-up Outcomes of Individualized Low-dose DOAC Therapy in Chinese Patients Aged 60 Years and Older: A Single-center Study | 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 Clinical Features and Follow-up Outcomes of Individualized Low-dose DOAC Therapy in Chinese Patients Aged 60 Years and Older: A Single-center Study Ruiqi Zhang, Jiali Du, Mei-Lin Liu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3800887/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 Introduction: It is common to adjust direct oral anticoagulant (DOAC) dosage individually according to the clinical characteristics and coagulation indexes of patients in clinical practice, but its effectiveness and safety are still controversial. The purpose of this study was to analyze the clinical characteristics and follow-up outcomes of elderly patients who adjusted anticoagulant therapy according to coagulation index. Method: Included were patients who were admitted to the geriatric Department of Peking University First Hospital from January 1, 2016 to December 31, 2021, with indications of anticoagulation therapy, receiving DOAC (Dabigatran, Rivaroxaban) therapy, individualized dose adjustment according to APTT (peak value of 46-60s) or AXA (peak value of 0.5-1.0IU/ml), aged ≥60 years, and complete clinical data. Outpatient or telephone follow-up every three months after discharge until termination or death or end of study (December 31, 2022). The clinical features and follow-up results of Dabigatran 110mg BID group and Dabigatran 110mg QD group, Rivaroxaban 5mg BID group and Rivaroxaban 2.5mg BID group were compared. Result: A total of 388 patients were enrolled, including 145 (35.1%) in the Dabigatrangroup and 243 (58.8%) in the rivaroxaban group. The Dabigatrangroup was divided into the 110mg BID group (85 cases) and the 110mg QD group (60 cases), and patients in the 110mg QD group were older, lighter, and had lower glomerular filtration rate (eGFR). The Rivaroxaban group was divided into the 5mg BID group (134 cases) and the 2.5mg BID group (109 cases), and patients in the 2.5mg BID group were older, weighed less, had lower activity of daily living (ADL) scores, and had lower eGFR. The mean follow-up time was 49.5±23.4 months in the Dabigatrangroup and 32.1±20.1 months in the Rivaroxaban group. Survival analysis of bleeding events, thrombotic events, and death was not significantly different between Dabigatran 110mgBID and 110mgQD and Rivaroxaban 5mgBID and 2.5mgBID groups. Conclusion: The clinical characteristics of patients with individualized low-dose DOAC regimen were as follows: age ≥80 years old, weight ≤60kg, ADL score ≤60 points, HAS-BLED score ≥3 points, eGFR < 60ml/min/1.73m², baseline hemoglobin < 120g/L. There was no significant difference in the incidence of bleeding and thrombotic events between individualized low-dose therapy based on patient clotting indicators and standard therapy. Direct oral anticoagulant Dabigatran Rivaroxaban Anti-factor Xa activity Aged Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction In recent years, direct oral anticoagulants (DOAC), including direct thrombin inhibitors (Dabigatran) and Factor Xa inhibitors (rivaroxaban), have been widely used in the clinic [1-3] . Since age is a risk factor for thromboembolism and bleeding, anticoagulation therapy in elderly patients has been in a dilemma. Although studies have shown that elderly patients can benefit from anticoagulation therapy, in clinical practice, the proportion of patients adopting DOAC standard anticoagulation regimen recommended by the guidelines is not high [4] . Individualized DOAC dose adjustment based on patients' clinical characteristics and coagulation indexes is relatively common in clinical practice, but its effectiveness and safety are still controversial [5-7] . The purpose of this study was to analyze the clinical characteristics and follow-up outcomes of elderly patients who adjusted anticoagulant therapy according to coagulation index. Method Inclusion criteria: Patients were admitted to the geriatric Department of Peking University First Hospital from January 1, 2016 to December 31, 2021, with indications of anticoagulant therapy, receiving DOAC(Dabigatran, rivaroxaban) therapy, dose adjusted according to APTT or AXA value, aged ≥60 years, and clinical data were complete. Exclusion criteria were: There is active bleeding before taking the drug. Severe liver function damage, transaminase or bilirubin ≥3 times the upper limit of normal; Severe renal function impairment, eGFR≤15ml/min/1.7㎡. Recently combined use of medium-strong P-glycoprotein inhibitors, such as ketoconazole, itraconazole, voriconazole, clarithromycin, erythromycin and other drugs. Recently combined with CYP3A4 inducers, such as phenytoin sodium, carbamazepine, phenobarbital and other drugs; Recent use of drugs that affect APTT or AXA results, such as ordinary heparin, low molecular weight heparin, etc. No complete clinical data. By accessing the hospital's electronic medical records, including cases and collecting medical history materials, It included sex, age, height, weight, ADL score (Barthel Index [8] ), anticoagulation regimen and dose, anticoagulation indication, CHA2DS2-VASc score, HAS-BLED score, laboratory indicators, complications and history. According to the pharmacokinetic characteristics, the trough concentration time of dabigatran and rivaroxaban was within 1 hour before the next administration, and the peak concentration time was 3 hours after the next administration. Blood samples were collected according to the above time [9, 10] . AXA applied fluorescence method, Werfen ACL-TOP-700 instrument, Werfen AXA reagent determination and record. Outpatient or telephone follow-up after discharge until termination or death or end of study (December 31, 2022). Patients receiving dabigatran were divided into 110mg BID group and 110mg QD group with the target value of 46-60s as the peak value of APTT 3 days after medication. Patients receiving rivaroxaban were divided into 5mg BID group and 2.5mg BID group with the AXA peak value of 0.5-1.0IU/ml adjusted dose at 3 days after taking rivaroxaban. Clinical characteristics and follow-up outcomes (bleeding, thrombotic events and death) of the above groups were analyzed and compared (Figure 1). Measurement data conforming to normal distribution were represented by Mean ±SD. Independent sample t test was used for comparison of mean between two groups, and ANOVA was used for comparison of mean between multiple groups. Measurement data that do not conform to the normal distribution are represented by the median and interquartile spacing, and non-parametric tests are used. Counting data are expressed by frequency and frequency, and X² test is used for comparison; If there is A theoretical frequency T < 1 or a practical frequency A=0 or a total number of cases n < 40 in the four-cell table, Fisher's test is used. Kaplan-Meier survival curve was used to analyze the relationship between anticoagulation regimen and bleeding events, ischemic events and death. P<0.05 for all tests was considered statistically significant. All statistical analyses were performed with SPSS® Statistics (IBM SPSS Statistics for Windows, version 27.0). In accordance with Chinese law, this study was authorized by the Ethics Review Committee of our hospital. Results A total of 388 patients receiving DOAC were enrolled in this study, including 145 (35.1%) in the Dabigatran group and 243 (58.8%) in the rivaroxaban group. Among the 145 patients in the Dabigatran group, 85 cases (58.6%) were in the 110mgBID group, with an average APTT peak value of 48.6±8.8s and APTT valley value of 41.2±6.9s; 60 cases (41.4%) were in the 110mgQD group, with an average APTT peak value of 51.1±10.9s. The APTT valley value was 41.1±8.5s, and there was no significant difference between the two groups in APTT valley and peak value. Compared with dabigatran 110mg BID group, Dabigatran 110mg QD group was older (83.4±7.1 years VS. 77.3±7.5 years, P < 0.001), and had a higher proportion of patients over 80 years old (70.0% VS. 37.6%, P=0.000). Lower body weight (66.6±13.4kg VS. 72.1±10.5kg, P=0.007), higher ha-bled score (2.4±1.0 VS. 2.0±1.0, P=0.034), There were no significant differences in male proportion, BMI, ADL score, anticoagulation indications and CHA2DS2-VASc score between the two groups. eGFR in Dabigatran 110mg QD group was lower than that in Dabigatran 110mg BID group (63.5±12.8 ml/min/1.73 m²VS. 68.5±13.1 ml/min/1.73 m², P=0.036). The proportion of patients in eGFR < 60 ml/min/1.73 m² group was higher (41.7% VS. 24.7%, P=0.017), and there were no statistically significant differences in HGB, PLT, ALT, AST, CREA, ARA and ADP between the two groups (Table 1.2). Table 1. Comparison of basic data of Dabigatran group patients Dabigatran (n=145) Dabigatran 110mg BID (n=85) Dabigatran 110mg QD (n=60) P male, n(%) 104(71.7) 64(75.3) 40(66.7) 0.256 Age (year), mean ± SD ˃80 years, n(%) 79.8±8.0 74(51.0) 77.3±7.5 32(37.6) 83.4±7.1 42(70.0) 0.000 0.000 Weight (kg), mean ± SD 69.9±12.0 72.1±10.5 66.6±13.4 0.007 BMI (kg/㎡), mean ± SD 25.0±3.3 25.3±2.9 24.4±3.8 0.149 ADL score, mean ± SD ≤60 score, n(%) 86.2±12.9 19(13.1) 87.1±19.9 11(12.9) 84.9±18.5 8(13.3) 0.498 0.945 Anticoagulation indication non-valvular atrial fibrillation, n(%) venous thromboembolism, n(%) 127(87.6) 18(12.4) 76(89.4) 9 (10.6) 51(85.0) 9 (15.0) 0.427 CHA2DS2-VASc score, mean ± SD 4.4±1.5 4.3±1.6 4.7±1.2 0.125 HAS-BLED score, mean ± SD 2.2±1.0 2.0±1.0 2.4±1.0 0.034 Table 2. Comparison of laboratory indicators in Dabigatran group Dabigatran (n=145) Dabigatran 110mg BID (n=85) Dabigatran 110mg QD (n=60) P HB (g/L), mean ± SD 130.5±16.0 130.6±16.4 130.4±15.8 0.916 PLT (10^9/L), mean ± SD 180.2±53.4 181.5±53.1 178.4±54.2 0.737 ALT (IU/L), mean ± SD 19.8±12.4 21.1±13.2 18.0±11.0 0.121 AST (IU/L), mean ± SD 24.2±14.4 23.5±13.0 25.3±16.3 0.496 CREA (umol /L), mean ± SD 88.9±18.2 88.9±16.5 88.8±20.5 0.952 eGFR, (ml/min/1.73㎡), mean±SD ˂60ml/min/1.73㎡, n(%) 66.5±13.2 46(31.7) 68.5±13.1 21(24.7) 63.5±12.8 25(41.7) 0.025 0.017 ARA(%), mean ± SD lack, n(%) 33.2±30.6 65(44.8) 29.7±27.9 25(44.6) 39.1±31.0 40(44.9) 0.103 ADP(%), mean ± SD lack, n(%) 57.7±14.3 68(46.9) 57.5±14.6 26(46.4) 58.0±14.1 42(47.2) 0.869 Of the 243 patients in rivaroxaban group, 134 (55.1%) were in the 5mgBID group, the average AXA peak value was 0.69±0.29IU/ml, the AXA valley value was 0.22±0.15IU/ml, and 109 (44.9%) were in the 2.5mgBID group. The average AXA peak value was 0.54±0.23IU/ml, and the AXA valley value was 0.18±0.12IU/ml. There was no statistical difference between the two groups. Compared with the rivaroxaban 5mg BID group, the rivaroxaban 2.5mg BID group was older (83.6±7.5 years VS. 76.6±8.2 years, P < 0.001) and had a higher proportion of patients over 80 years of age (73.4% VS. 37.3%, P < 0.001). Lower body weight (65.0±12.0kg VS. 71.5±11.5kg, P < 0.001), lower ADL scores (72.4±22.4 VS. 88.5±11.3, P=0.000), and a higher proportion of patients with persistent atrial fibrillation (32.1% VS. 27.6%, P=0.048), the CHA2DS2-VASc score was higher (4.7±1.3 VS. 3.9±1.5, P < 0.001), and the hasbled score was higher (2.4±0.9 VS. 1.8±0.9, P < 0.001). There were no significant differences in the proportion of males and the indications for anticoagulation between the two groups. Compared with rivaroxaban 5mgBID group, Rivaroxaban 2.5mgBID group had a lower HGB (120.2±19.2g/L VS. 132.1±16.1g/L, P=0.000). eGFR was lower (60.9±19.2 ml/min/1.73 m² VS. 70.0±15.4 ml/min/1.73 m², P=0.002), and the proportion of patients with eGFR < 60 ml/min/1.73 m² was higher (40.4% VS. 21.6%, P=0.001). There were no significant differences in PLT, ALT, AST, CREA, ARA and ADP between the two groups (Table 3.4). Table 3. Comparison of basic data of Rivaroxaban group patients Rivaroxaban (n=243) Rivaroxaban 5mg BID (n=134) Rivaroxaban 2.5mg BID (n=109) P male, n(%) 180(74.1) 105(78.4) 75(68.8) 0.091 Age (year), mean ± SD ˃80 years, n(%) 79.7±8.5 130(53.5) 76.6±8.2 50(37.3) 83.6±7.5 80(73.4) 0.000 0.000 Weight (kg), mean ± SD 68.7±12.1 71.5±11.5 65.0±12.0 0.000 BMI (kg/㎡), mean ± SD 24.4±3.7 25.1±3.6 23.4±3.6 0.001 ADL score, mean ± SD ≤60 score, n(%) 81.3±26.0 49(20.2) 88.5±11.3 16(11.9) 72.4±22.4 33 (30.3) 0.000 0.000 Anticoagulation indication non-valvular atrial fibrillation, n(%) venous thromboembolism, n(%) 154(63.4) 89(36.6) 92(68.7) 42 (31.3) 62(56.9) 47(43.1) 0.058 CHA2DS2-VASc score, mean ± SD 4.2±1.5 3.9±1.5 4.7±1.3 0.000 HAS-BLED score, mean ± SD 2.0±1.0 1.8±0.9 2.4±0.9 0.000 Table 4. Comparison of laboratory indicators in Rivaroxaban group Rivaroxaban (n=243) Rivaroxaban 5mg BID (n=134) Rivaroxaban 2.5mg BID (n=109) P HB (g/L), mean ± SD 126.8±18.4 132.1±16.1 120.2±19.2 0.000 PLT (10^9/L), mean ± SD 191.4±74.1 197.4±91.0 184.0±64.3 0.162 ALT (IU/L), mean ± SD 20.6±16.4 21.4±14.7 19.7±18.4 0.418 AST (IU/L), mean ± SD 26.2±20.4 24.6±10.4 28.1±28.1 0.224 CREA (umol/L), mean ± SD 91.3±31.7 88.7±21.3 94.6±40.9 0.171 eGFR, (ml/min/1.73㎡), mean±SD ˂60ml/min/1.73㎡, n(%) 66.8±17.5 43(30.1) 70.0±15.4 29(21.6) 60.9±19.2 44(40.4) 0.002 0.001 ARA(%), mean ± SD lack, n(%) 28.5±25.3 113(46.5) 29.2±25.1 63(47.0) 27.9±25.4 50(45.9) 0.961 ADP(%), mean ± SD lack, n(%) 54.4±17.2 118(48.6) 57.0±16.8 65(48.5) 51.2±17.3 53(48.6) 0.065 The mean follow-up time in the Dabiga group was 49.5±23.4 months. Compared with dabigatran 110mg BID group, the proportion of long-term maintenance was lower in the dabigatran 110mg QD group (45.0% VS. 70.6%, P=0.008). There was no significant difference in follow-up outcomes between the other two groups. The isogeneity test of survival analysis for bleeding events was performed between Dabigatran 110mg BID group and 110mg QD group, and the chi-square value of Log Rank was 0.180, P=0.671, with no statistical significance. Isogeneity test of survival analysis for thrombotic events was performed between Dabigatran 110mg BID group and 110mg QD group, and the Log Rank chi-square value was 0.021, P=0.886, with no statistical significance. The isogeneity test of survival analysis for death was performed between Dabigatran 110mg BID group and 110mg QD group, and the chi-square value of Log Rank was 2.594, P=0.107, with no statistical significance (Figure 2-4). The mean follow-up time of the rivaroxaban group was 32.1±20.1 months. The rivaroxaban 2.5mg BID group had a lower rate of long-term maintenance (61.6% VS. 79.9%, P=0.000) and a higher mortality rate (25.7% VS. 7.5%, P=0.001) than the rivaroxaban 5mg BID group. Non-cardiogenic mortality was higher (20.2% VS. 4.5%, P=0.000). There was no significant difference in follow-up outcomes between the other two groups. In the survival analysis distribution equality test for bleeding events between the rivaroxaban 5mg BID group and the 2.5mg BID group, the Log-Rank Chi-square value was 0.732, P=0.392, and the difference was not statistically significant. The distribution of survival analysis for thrombotic events in the rivaroxaban 5mg BID group and 2.5mg BID group was identical, and the Log-Rank Chi-square value was 0.615, P=0.433, with no statistical significance. The equivalence test of survival analysis for death between the rivaroxaban 5mg BID group and the 2.5mg BID group showed that the Log-Rank Chi-square value was 11.530, P=0.001, and the difference was not statistically significant (Figure 5-7). Discussion The patients included in this study are the elderly population, more than half of them are over 80 years old, and the risk of bleeding and thrombosis is high, and there are more complications and combined drugs. Anticoagulant drugs and specific dosage plan are determined and adjusted by clinicians according to the general conditions and coagulation indexes of patients, which reflects the clinical reality of individualized anticoagulant therapy in elderly patients in China to a certain extent. In clinical work, the clinician adjusts the DOAC dose according to the patient's specific situation. Studies have shown that DOAC dose can be reduced in patients with the following clinical characteristics: elderly (≥ 75 years old), female, low weight (≤ 60kg), renal insufficiency (CrCl ≤ 50ml/min), previous bleeding history, combined history of hypertension, combined use of dronedarone or antiplatelet drugs, etc. [ 11 ] Studies have shown that Asian patients with low body weight, cancer, low baseline hemoglobin levels, prolonged prothrombin time, and low creatinine clearance are at increased risk of edoxaban related bleeding [ 12 – 14 ] . This study found that the clinical characteristics of patients taking low-dose DOAC regimen included: age ≥ 80 years old, weight ≤ 60kg, ADL score ≤ 60 points, HAS-BLED score ≥ 3.0 points, eGFR < 60ml/min/1.73m², and baseline hemoglobin < 120g/L. In this study, there was no difference in the survival analysis of bleeding events, thrombotic events, and death in the two dabigatran dose groups, and the incidence was lower than in previous studies. Both doses of rivaroxaban were not the recommended dose, and the incidence of major bleeding was 0% in the 5mg BID group and the 2.5mg BID group. 0%) and the incidence of thrombosis (2.2%; 2.7%) were lower than previous studies [ 15 ] . The above results showed that in elderly people with high bleeding risk, the incidence of bleeding events did not increase and the incidence of thrombotic events decreased with the anticoagulation program formulated by individualized therapy, suggesting that there are clinical benefits of individualized DOAC therapy in elderly people. In this study, compared with the two doses of rivaroxaban, the 2.5mg BID group had a higher mortality rate (26.6% VS. 7.5%, P = 0.000) and a higher non-cardiogenic mortality rate (20.2% VS. 4.5%, P = 0.000). There was no significant difference in the incidence of bleeding events and thrombotic events. There was no difference in the survival analysis of bleeding events, thrombotic events and death in the rivaroxaban group. Although mortality was higher in the rivaroxaban 2.5mg BID group, survival analyses of death were not significantly different between the two groups, and the cause of death was more non-cardiogenic, which was considered to be associated with older patients enrolled in the 2.5mg BID group, worse general conditions, and more comorbidities. In this study, the correlation analysis between different doses and outcome events was limited by the number of enrolled cases and the influence of other clinical factors on outcome was not considered, which had certain limitations. The analysis could be further expanded after the sample size was adjusted for confounding factors. Conclusions The clinical characteristics of patients with individualized low-dose DOAC regimen were as follows: age ≥ 80 years old, weight ≤ 60kg, ADL score ≤ 60 points, HAS-BLED score ≥ 3 points, eGFR < 60ml/min/1.73m², baseline hemoglobin < 120g/L. There was no significant difference in the incidence of bleeding and thrombotic events between individualized low-dose therapy based on patient clotting indicators and standard therapy. Declarations Ethical Approval and Informed Consent to Participate Patient’s identity is not disclosed anywhere, and informed consent has been obtained from all subjects and/or their legal guardians. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Consent for Publication Not applicable for this segment. Availability of data and materials The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request. Funding information None. Conflict of interest The authors declare that they have no conflict of interest. Authors’ contributions Conception or design of the work: RZ; data collection: RZ; data analysis and interpretation: RZ; drafting the article: RZ; critical revision of the article: JD, ML; final approval of the version to be published: RZ, JD, ML References Rose D K, Bar B, Direct Oral Anticoagulant Agents: Pharmacologic Profile, Indications, Coagulation Monitoring, and Reversal Agents [J], J Stroke Cerebrovasc Dis, 2018, 27(8): 2049-2058. Srikajornlarp S, Amnueypol M, Vathesatogkit P, et al., Effectiveness and Safety of Direct Oral Anticoagulants in Thai Patients with Atrial Fibrillation: A Real-World Retrospective Cohort Study [J], Clin Appl Thromb Hemost, 2022, 28: 10760296221130058. Alosaimi H M, Alqahtani S, Balkhi B, et al., A retrospective study of real-world effectiveness and safety of rivaroxaban in patients with non-valvular atrial fibrillation and venous thromboembolism in Saudi Arabia [J], PeerJ, 2022, 10: e13974. 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Kvasnicka T, Malikova I, Zenahlikova Z, et al., Rivaroxaban - Metabolism, Pharmacologic Properties and Drug Interactions [J], Curr Drug Metab, 2017, 18(7): 636-642. Zhang H, Liu Z, Mu G, et al., Diagnostic performance of coagulation indices for direct oral anticoagulant concentration [J], Thromb Res, 2020, 195: 171-179. Lee S R, Lee Y S, Park J S, et al., Label Adherence for Non-Vitamin K Antagonist Oral Anticoagulants in a Prospective Cohort of Asian Patients with Atrial Fibrillation [J], Yonsei Med J, 2019, 60(3): 277-284. Mikami T, Hirabayashi K, Okawa K, et al., Laboratory Test Predictors for Major Bleeding in Elderly (≥80 Years) Patients With Nonvalvular Atrial Fibrillation Treated With Edoxaban 15 mg: Sub-Analysis of the ELDERCARE-AF Trial [J], Journal of the American Heart Association, 2022, 11(17): e024970. Lee O S, Kim W, Jang B M, et al., Association of risk factors and bleeding complications in Asian patients taking edoxaban [J], Br J Clin Pharmacol, 2021, 87(4): 2121-2127. Takase T, Ikesue H, Nakagawa H, et al., Risk Factors for Major Bleeding and Clinically Relevant Non-major Bleeding in Japanese Patients Treated with Edoxaban [J], Biol Pharm Bull, 2020, 43(3): 458-462. Halperin J L, Hankey G J, Wojdyla D M, et al., Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) [J], Circulation, 2014, 130(2): 138-146. 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. 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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-3800887","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264160857,"identity":"5904bb63-137c-403d-997e-c8ba1a3c106a","order_by":0,"name":"Ruiqi Zhang","email":"","orcid":"","institution":"Peking University First Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ruiqi","middleName":"","lastName":"Zhang","suffix":""},{"id":264160858,"identity":"149200a4-5b22-477a-80d1-99992415ee5c","order_by":1,"name":"Jiali Du","email":"","orcid":"","institution":"Peking University First Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jiali","middleName":"","lastName":"Du","suffix":""},{"id":264160859,"identity":"4b37c0e5-ef0d-4952-a676-5693b34e5389","order_by":2,"name":"Mei-Lin Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYBACPmYQaWDBw8DeAxbg4SOkhQ2iRYKHgecMA8MBoBY2gloglAQQ5YC1MBDWws5juuFDgYSMueTbg48/5tjJsDEwP3x0A6/DeMxuzgA6zHJ2XrLBwW3JQIexGRvnENBymweoxeB2jpnEwW3MQC08bNIEtfwBabl5BqSlnkgtoBAzuMED0nKYGC1sZTd7QFrO5BgbnN12nAcogt8v/PyHt9348cfG3uD4GcMHlduq7fnZmx8+xqcFC2AmTfkoGAWjYBSMAiwAABBJOysQLZGhAAAAAElFTkSuQmCC","orcid":"","institution":"Peking University First Hospital","correspondingAuthor":true,"prefix":"","firstName":"Mei-Lin","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2023-12-24 15:14:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3800887/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3800887/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49073313,"identity":"75e07eb7-5b07-480e-8aa1-937dd9a1c24c","added_by":"auto","created_at":"2024-01-02 17:33:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":25552,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flow chart (APTT: activated partial thromboplastin time, AXA: Anti-factor XA activity)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3800887/v1/b2d35e6b675e4156d1ed2165.png"},{"id":49072446,"identity":"2c16761b-d010-4145-9d07-29c060c375d7","added_by":"auto","created_at":"2024-01-02 17:17:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":21957,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analysis function of the distribution of survival analysis for bleeding events in the Dabigatran 110mg BID group and 110mg QD group\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3800887/v1/dcbfeadd2078bdb11f42564b.png"},{"id":49072448,"identity":"cbf44aad-20aa-4d46-b534-d76c993aa752","added_by":"auto","created_at":"2024-01-02 17:17:26","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":18999,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analysis function of isogeneity test for survival analysis distribution of death in Dabigatran 110mg BID group and 110mg QD group\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3800887/v1/5c9a531e14e18208fd3d2923.png"},{"id":49072451,"identity":"a0ab1a04-e1d1-4e13-86de-389e0bafe952","added_by":"auto","created_at":"2024-01-02 17:17:26","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":19670,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analysis function of isogeneity test for survival analysis distribution of death in Dabigatran 110mg BID group and 110mg QD group\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3800887/v1/f429a3e59b0c181465ecd852.png"},{"id":49073092,"identity":"7d310fa9-5858-41d7-824d-fed4bd8c1f45","added_by":"auto","created_at":"2024-01-02 17:25:26","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":20738,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analysis function of the distribution of survival analysis for bleeding events in the rivaroxaban 5mg BID group and 2.5mg BID group\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-3800887/v1/b195471c956011ce9b595323.png"},{"id":49073093,"identity":"e00b323b-eb42-47b9-a1ed-f94be233c597","added_by":"auto","created_at":"2024-01-02 17:25:26","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":19192,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analysis function of the distribution of survival analysis for thrombotic events in the rivaroxaban 5mg BID group and 2.5mg BID group\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-3800887/v1/61ab4b48e3cb5e1fa0d6694f.png"},{"id":49072452,"identity":"dea604ce-2b1b-49e5-aa35-04ad073dad6f","added_by":"auto","created_at":"2024-01-02 17:17:26","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":20427,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analysis function of the distribution of survival analysis for thrombotic events in the rivaroxaban 5mg BID group and 2.5mg BID group\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-3800887/v1/3147c801a1d7a6248421d1e8.png"},{"id":51997049,"identity":"acf57e4a-0403-4f72-ab10-5acdf1502c32","added_by":"auto","created_at":"2024-03-05 06:29:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":316800,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3800887/v1/370e3848-6f62-4de2-91f9-9e2b14f7033d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Features and Follow-up Outcomes of Individualized Low-dose DOAC Therapy in Chinese Patients Aged 60 Years and Older: A Single-center Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn recent years, direct oral anticoagulants (DOAC), including direct thrombin inhibitors (Dabigatran) and Factor Xa inhibitors (rivaroxaban), have been widely used in the clinic\u003csup\u003e[1-3]\u003c/sup\u003e. Since age is a risk factor for thromboembolism and bleeding, anticoagulation therapy in elderly patients has been in a dilemma. Although studies have shown that elderly patients can benefit from anticoagulation therapy, in clinical practice, the proportion of patients adopting DOAC standard anticoagulation regimen recommended by the guidelines is not high\u003csup\u003e[4]\u003c/sup\u003e . Individualized DOAC dose adjustment based on patients\u0026apos; clinical characteristics and coagulation indexes is relatively common in clinical practice, but its effectiveness and safety are still controversial\u003csup\u003e[5-7]\u003c/sup\u003e. The purpose of this study was to analyze the clinical characteristics and follow-up outcomes of elderly patients who adjusted anticoagulant therapy according to coagulation index.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eInclusion criteria: Patients were admitted to the geriatric Department of Peking University First Hospital from January 1, 2016 to December 31, 2021, with indications of anticoagulant therapy, receiving DOAC(Dabigatran, rivaroxaban) therapy, dose adjusted according to APTT or AXA value, aged \u0026ge;60 years, and clinical data were complete. Exclusion criteria were: There is active bleeding before taking the drug. Severe liver function damage, transaminase or bilirubin \u0026ge;3 times the upper limit of normal; Severe renal function impairment, eGFR\u0026le;15ml/min/1.7㎡. Recently combined use of medium-strong P-glycoprotein inhibitors, such as ketoconazole, itraconazole, voriconazole, clarithromycin, erythromycin and other drugs. Recently combined with CYP3A4 inducers, such as phenytoin sodium, carbamazepine, phenobarbital and other drugs; Recent use of drugs that affect APTT or AXA results, such as ordinary heparin, low molecular weight heparin, etc. No complete clinical data.\u003c/p\u003e\n\u003cp\u003eBy accessing the hospital\u0026apos;s electronic medical records, including cases and collecting medical history materials, It included sex, age, height, weight, ADL score (Barthel Index\u003csup\u003e[8]\u003c/sup\u003e), anticoagulation regimen and dose, anticoagulation indication, CHA2DS2-VASc score, HAS-BLED score, laboratory indicators, complications and history. According to the pharmacokinetic characteristics, the trough concentration time of dabigatran and rivaroxaban was within 1 hour before the next administration, and the peak concentration time was 3 hours after the next administration. Blood samples were collected according to the above time\u003csup\u003e[9, 10]\u003c/sup\u003e. AXA applied fluorescence method, Werfen ACL-TOP-700 instrument, Werfen AXA reagent determination and record. Outpatient or telephone follow-up after discharge until termination or death or end of study (December 31, 2022).\u003c/p\u003e\n\u003cp\u003ePatients receiving dabigatran were divided into 110mg BID group and 110mg QD group with the target value of 46-60s as the peak value of APTT 3 days after medication. Patients receiving rivaroxaban were divided into 5mg BID group and 2.5mg BID group with the AXA peak value of 0.5-1.0IU/ml adjusted dose at 3 days after taking rivaroxaban. Clinical characteristics and follow-up outcomes (bleeding, thrombotic events and death) of the above groups were analyzed and compared (Figure 1).\u003c/p\u003e\n\u003cp\u003eMeasurement data conforming to normal distribution were represented by Mean \u0026plusmn;SD. Independent sample t test was used for comparison of mean between two groups, and ANOVA was used for comparison of mean between multiple groups. Measurement data that do not conform to the normal distribution are represented by the median and interquartile spacing, and non-parametric tests are used. Counting data are expressed by frequency and frequency, and X\u0026sup2; test is used for comparison; If there is A theoretical frequency T \u0026lt; 1 or a practical frequency A=0 or a total number of cases n \u0026lt; 40 in the four-cell table, Fisher\u0026apos;s test is used. Kaplan-Meier survival curve was used to analyze the relationship between anticoagulation regimen and bleeding events, ischemic events and death. P\u0026lt;0.05 for all tests was considered statistically significant. All statistical analyses were performed with SPSS\u0026reg; Statistics (IBM SPSS Statistics for Windows, version 27.0).\u003c/p\u003e\n\u003cp\u003eIn accordance with Chinese law, this study was authorized by the Ethics Review Committee of our hospital. \u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 388 patients receiving DOAC were enrolled in this study, including 145 (35.1%) in the Dabigatran group and 243 (58.8%) in the rivaroxaban group.\u003c/p\u003e\n\u003cp\u003eAmong the 145 patients in the Dabigatran group, 85 cases (58.6%) were in the 110mgBID group, with an average APTT peak value of 48.6\u0026plusmn;8.8s and APTT valley value of 41.2\u0026plusmn;6.9s; 60 cases (41.4%) were in the 110mgQD group, with an average APTT peak value of 51.1\u0026plusmn;10.9s. The APTT valley value was 41.1\u0026plusmn;8.5s, and there was no significant difference between the two groups in APTT valley and peak value. Compared with dabigatran 110mg BID group, Dabigatran 110mg QD group was older (83.4\u0026plusmn;7.1 years VS. 77.3\u0026plusmn;7.5 years, P \u0026lt; 0.001), and had a higher proportion of patients over 80 years old (70.0% VS. 37.6%, P=0.000). Lower body weight (66.6\u0026plusmn;13.4kg VS. 72.1\u0026plusmn;10.5kg, P=0.007), higher ha-bled score (2.4\u0026plusmn;1.0 VS. 2.0\u0026plusmn;1.0, P=0.034), There were no significant differences in male proportion, BMI, ADL score, anticoagulation indications and CHA2DS2-VASc score between the two groups. eGFR in Dabigatran 110mg QD group was lower than that in Dabigatran 110mg BID group (63.5\u0026plusmn;12.8 ml/min/1.73 m\u0026sup2;VS. 68.5\u0026plusmn;13.1 ml/min/1.73 m\u0026sup2;, P=0.036). The proportion of patients in eGFR \u0026lt; 60 ml/min/1.73 m\u0026sup2; group was higher (41.7% VS. 24.7%, P=0.017), and there were no statistically significant differences in HGB, PLT, ALT, AST, CREA, ARA and ADP between the two groups (Table 1.2).\u003c/p\u003e\n\u003cp\u003eTable 1. Comparison of basic data of Dabigatran group patients\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"623\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.77564102564103%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003eDabigatran (n=145)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003eDabigatran 110mg BID (n=85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003eDabigatran 110mg QD (n=60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.224358974358974%\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.77564102564103%\"\u003e\n \u003cp\u003emale, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e104(71.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e64(75.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e40(66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.224358974358974%\"\u003e\n \u003cp\u003e0.256\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.77564102564103%\"\u003e\n \u003cp\u003eAge (year), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; ˃80 years, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e79.8\u0026plusmn;8.0\u003c/p\u003e\n \u003cp\u003e74(51.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e77.3\u0026plusmn;7.5\u003c/p\u003e\n \u003cp\u003e32(37.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e83.4\u0026plusmn;7.1\u003c/p\u003e\n \u003cp\u003e42(70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.224358974358974%\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.77564102564103%\"\u003e\n \u003cp\u003eWeight (kg), mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e69.9\u0026plusmn;12.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e72.1\u0026plusmn;10.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e66.6\u0026plusmn;13.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.224358974358974%\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.77564102564103%\"\u003e\n \u003cp\u003eBMI (kg/㎡), mean \u0026plusmn; SD \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e25.0\u0026plusmn;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e25.3\u0026plusmn;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e24.4\u0026plusmn;3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.224358974358974%\"\u003e\n \u003cp\u003e0.149\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.77564102564103%\"\u003e\n \u003cp\u003eADL score, mean \u0026plusmn; SD \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026le;60 score, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e86.2\u0026plusmn;12.9\u003c/p\u003e\n \u003cp\u003e19(13.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e87.1\u0026plusmn;19.9\u003c/p\u003e\n \u003cp\u003e11(12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e84.9\u0026plusmn;18.5\u003c/p\u003e\n \u003cp\u003e8(13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.224358974358974%\"\u003e\n \u003cp\u003e0.498\u003c/p\u003e\n \u003cp\u003e0.945\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.77564102564103%\"\u003e\n \u003cp\u003eAnticoagulation indication \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003enon-valvular atrial fibrillation, n(%)\u003c/p\u003e\n \u003cp\u003evenous thromboembolism, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e127(87.6)\u003c/p\u003e\n \u003cp\u003e18(12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e76(89.4)\u003c/p\u003e\n \u003cp\u003e9\u0026nbsp;(10.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e51(85.0)\u003c/p\u003e\n \u003cp\u003e9\u0026nbsp;(15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.224358974358974%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.427\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.77564102564103%\"\u003e\n \u003cp\u003eCHA2DS2-VASc score, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e4.4\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e4.3\u0026plusmn;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e4.7\u0026plusmn;1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.224358974358974%\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.77564102564103%\"\u003e\n \u003cp\u003eHAS-BLED score, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e2.2\u0026plusmn;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e2.0\u0026plusmn;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e2.4\u0026plusmn;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.224358974358974%\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2. Comparison of laboratory indicators in Dabigatran group\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"629\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.53968253968254%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003eDabigatran (n=145)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41269841269841%\"\u003e\n \u003cp\u003eDabigatran 110mg BID (n=85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003eDabigatran 110mg QD (n=60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.80952380952381%\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.53968253968254%\"\u003e\n \u003cp\u003eHB (g/L), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e130.5\u0026plusmn;16.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41269841269841%\"\u003e\n \u003cp\u003e130.6\u0026plusmn;16.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e130.4\u0026plusmn;15.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.80952380952381%\"\u003e\n \u003cp\u003e0.916\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.53968253968254%\"\u003e\n \u003cp\u003ePLT (10^9/L), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e180.2\u0026plusmn;53.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41269841269841%\"\u003e\n \u003cp\u003e181.5\u0026plusmn;53.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e178.4\u0026plusmn;54.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.80952380952381%\"\u003e\n \u003cp\u003e0.737\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.53968253968254%\"\u003e\n \u003cp\u003eALT (IU/L), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e19.8\u0026plusmn;12.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41269841269841%\"\u003e\n \u003cp\u003e21.1\u0026plusmn;13.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e18.0\u0026plusmn;11.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.80952380952381%\"\u003e\n \u003cp\u003e0.121\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.53968253968254%\"\u003e\n \u003cp\u003eAST (IU/L), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e24.2\u0026plusmn;14.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41269841269841%\"\u003e\n \u003cp\u003e23.5\u0026plusmn;13.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e25.3\u0026plusmn;16.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.80952380952381%\"\u003e\n \u003cp\u003e0.496\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.53968253968254%\"\u003e\n \u003cp\u003eCREA (umol /L), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e88.9\u0026plusmn;18.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41269841269841%\"\u003e\n \u003cp\u003e88.9\u0026plusmn;16.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e88.8\u0026plusmn;20.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.80952380952381%\"\u003e\n \u003cp\u003e0.952\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.53968253968254%\"\u003e\n \u003cp\u003eeGFR, (ml/min/1.73㎡), mean\u0026plusmn;SD\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; ˂60ml/min/1.73㎡, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e66.5\u0026plusmn;13.2\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e46(31.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41269841269841%\"\u003e\n \u003cp\u003e68.5\u0026plusmn;13.1\u003c/p\u003e\n \u003cp\u003e21(24.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e63.5\u0026plusmn;12.8 \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25(41.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.80952380952381%\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.53968253968254%\"\u003e\n \u003cp\u003eARA(%), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; lack, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e33.2\u0026plusmn;30.6\u003c/p\u003e\n \u003cp\u003e65(44.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41269841269841%\"\u003e\n \u003cp\u003e29.7\u0026plusmn;27.9\u003c/p\u003e\n \u003cp\u003e25(44.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e39.1\u0026plusmn;31.0\u003c/p\u003e\n \u003cp\u003e40(44.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.80952380952381%\"\u003e\n \u003cp\u003e0.103\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.53968253968254%\"\u003e\n \u003cp\u003eADP(%), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; lack, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003e57.7\u0026plusmn;14.3\u003c/p\u003e\n \u003cp\u003e68(46.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.41269841269841%\"\u003e\n \u003cp\u003e57.5\u0026plusmn;14.6\u003c/p\u003e\n \u003cp\u003e26(46.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e58.0\u0026plusmn;14.1\u003c/p\u003e\n \u003cp\u003e42(47.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.80952380952381%\"\u003e\n \u003cp\u003e0.869\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eOf the 243 patients in rivaroxaban group, 134 (55.1%) were in the 5mgBID group, the average AXA peak value was 0.69\u0026plusmn;0.29IU/ml, the AXA valley value was 0.22\u0026plusmn;0.15IU/ml, and 109 (44.9%) were in the 2.5mgBID group. The average AXA peak value was 0.54\u0026plusmn;0.23IU/ml, and the AXA valley value was 0.18\u0026plusmn;0.12IU/ml. There was no statistical difference between the two groups. Compared with the rivaroxaban 5mg BID group, the rivaroxaban 2.5mg BID group was older (83.6\u0026plusmn;7.5 years VS. 76.6\u0026plusmn;8.2 years, P \u0026lt; 0.001) and had a higher proportion of patients over 80 years of age (73.4% VS. 37.3%, P \u0026lt; 0.001). Lower body weight (65.0\u0026plusmn;12.0kg VS. 71.5\u0026plusmn;11.5kg, P \u0026lt; 0.001), lower ADL scores (72.4\u0026plusmn;22.4 VS. 88.5\u0026plusmn;11.3, P=0.000), and a higher proportion of patients with persistent atrial fibrillation (32.1% VS. 27.6%, P=0.048), the CHA2DS2-VASc score was higher (4.7\u0026plusmn;1.3 VS. 3.9\u0026plusmn;1.5, P \u0026lt; 0.001), and the hasbled score was higher (2.4\u0026plusmn;0.9 VS. 1.8\u0026plusmn;0.9, P \u0026lt; 0.001). There were no significant differences in the proportion of males and the indications for anticoagulation between the two groups. Compared with rivaroxaban 5mgBID group, Rivaroxaban 2.5mgBID group had a lower HGB (120.2\u0026plusmn;19.2g/L VS. 132.1\u0026plusmn;16.1g/L, P=0.000). eGFR was lower (60.9\u0026plusmn;19.2 ml/min/1.73 m\u0026sup2; VS. 70.0\u0026plusmn;15.4 ml/min/1.73 m\u0026sup2;, P=0.002), and the proportion of patients with eGFR \u0026lt; 60 ml/min/1.73 m\u0026sup2; was higher (40.4% VS. 21.6%, P=0.001). There were no significant differences in PLT, ALT, AST, CREA, ARA and ADP between the two groups (Table 3.4).\u003c/p\u003e\n\u003cp\u003eTable 3. Comparison of basic data of Rivaroxaban group patients\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"595\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.27731092436975%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003eRivaroxaban (n=243)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.991596638655462%\"\u003e\n \u003cp\u003eRivaroxaban 5mg BID (n=134)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003eRivaroxaban 2.5mg BID (n=109)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.77310924369748%\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.27731092436975%\"\u003e\n \u003cp\u003emale, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e180(74.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.991596638655462%\"\u003e\n \u003cp\u003e105(78.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e75(68.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.77310924369748%\"\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.27731092436975%\"\u003e\n \u003cp\u003eAge (year), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; ˃80 years, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e79.7\u0026plusmn;8.5\u003c/p\u003e\n \u003cp\u003e130(53.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.991596638655462%\"\u003e\n \u003cp\u003e76.6\u0026plusmn;8.2\u003c/p\u003e\n \u003cp\u003e50(37.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e83.6\u0026plusmn;7.5\u003c/p\u003e\n \u003cp\u003e80(73.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.77310924369748%\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.27731092436975%\"\u003e\n \u003cp\u003eWeight (kg), mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e68.7\u0026plusmn;12.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.991596638655462%\"\u003e\n \u003cp\u003e71.5\u0026plusmn;11.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e65.0\u0026plusmn;12.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.77310924369748%\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.27731092436975%\"\u003e\n \u003cp\u003eBMI (kg/㎡), mean \u0026plusmn; SD \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e24.4\u0026plusmn;3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.991596638655462%\"\u003e\n \u003cp\u003e25.1\u0026plusmn;3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e23.4\u0026plusmn;3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.77310924369748%\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.27731092436975%\"\u003e\n \u003cp\u003eADL score, mean \u0026plusmn; SD \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026le;60 score, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e81.3\u0026plusmn;26.0\u003c/p\u003e\n \u003cp\u003e49(20.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.991596638655462%\"\u003e\n \u003cp\u003e88.5\u0026plusmn;11.3\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16(11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e72.4\u0026plusmn;22.4\u003c/p\u003e\n \u003cp\u003e33\u0026nbsp;(30.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.77310924369748%\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.27731092436975%\"\u003e\n \u003cp\u003eAnticoagulation indication \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003enon-valvular atrial fibrillation, n(%)\u003c/p\u003e\n \u003cp\u003evenous thromboembolism, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e154(63.4)\u003c/p\u003e\n \u003cp\u003e89(36.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.991596638655462%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e92(68.7)\u003c/p\u003e\n \u003cp\u003e42\u0026nbsp;(31.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e62(56.9)\u003c/p\u003e\n \u003cp\u003e47(43.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.77310924369748%\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.27731092436975%\"\u003e\n \u003cp\u003eCHA2DS2-VASc score, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e4.2\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.991596638655462%\"\u003e\n \u003cp\u003e3.9\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e4.7\u0026plusmn;1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.77310924369748%\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.27731092436975%\"\u003e\n \u003cp\u003eHAS-BLED score, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e2.0\u0026plusmn;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.991596638655462%\"\u003e\n \u003cp\u003e1.8\u0026plusmn;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.478991596638654%\"\u003e\n \u003cp\u003e2.4\u0026plusmn;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.77310924369748%\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 4. Comparison of laboratory indicators in Rivaroxaban group\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"595\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.45117845117845%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003eRivaroxaban (n=243)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50841750841751%\"\u003e\n \u003cp\u003eRivaroxaban 5mg BID (n=134)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003eRivaroxaban 2.5mg BID (n=109)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.993265993265993%\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.45117845117845%\"\u003e\n \u003cp\u003eHB (g/L), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e126.8\u0026plusmn;18.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50841750841751%\"\u003e\n \u003cp\u003e132.1\u0026plusmn;16.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e120.2\u0026plusmn;19.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.993265993265993%\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.45117845117845%\"\u003e\n \u003cp\u003ePLT (10^9/L), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e191.4\u0026plusmn;74.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50841750841751%\"\u003e\n \u003cp\u003e197.4\u0026plusmn;91.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e184.0\u0026plusmn;64.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.993265993265993%\"\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.45117845117845%\"\u003e\n \u003cp\u003eALT (IU/L), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e20.6\u0026plusmn;16.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50841750841751%\"\u003e\n \u003cp\u003e21.4\u0026plusmn;14.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e19.7\u0026plusmn;18.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.993265993265993%\"\u003e\n \u003cp\u003e0.418\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.45117845117845%\"\u003e\n \u003cp\u003eAST (IU/L), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e26.2\u0026plusmn;20.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50841750841751%\"\u003e\n \u003cp\u003e24.6\u0026plusmn;10.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e28.1\u0026plusmn;28.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.993265993265993%\"\u003e\n \u003cp\u003e0.224\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.45117845117845%\"\u003e\n \u003cp\u003eCREA (umol/L), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e91.3\u0026plusmn;31.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50841750841751%\"\u003e\n \u003cp\u003e88.7\u0026plusmn;21.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e94.6\u0026plusmn;40.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.993265993265993%\"\u003e\n \u003cp\u003e0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.45117845117845%\"\u003e\n \u003cp\u003eeGFR, (ml/min/1.73㎡), mean\u0026plusmn;SD\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; ˂60ml/min/1.73㎡, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e66.8\u0026plusmn;17.5\u003c/p\u003e\n \u003cp\u003e43(30.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50841750841751%\"\u003e\n \u003cp\u003e70.0\u0026plusmn;15.4\u003c/p\u003e\n \u003cp\u003e29(21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e60.9\u0026plusmn;19.2\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e44(40.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.993265993265993%\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.45117845117845%\"\u003e\n \u003cp\u003eARA(%), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; lack, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e28.5\u0026plusmn;25.3\u003c/p\u003e\n \u003cp\u003e113(46.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50841750841751%\"\u003e\n \u003cp\u003e29.2\u0026plusmn;25.1\u003c/p\u003e\n \u003cp\u003e63(47.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e27.9\u0026plusmn;25.4\u003c/p\u003e\n \u003cp\u003e50(45.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.993265993265993%\"\u003e\n \u003cp\u003e0.961\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.45117845117845%\"\u003e\n \u003cp\u003eADP(%), mean \u0026plusmn; SD\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; lack, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e54.4\u0026plusmn;17.2\u003c/p\u003e\n \u003cp\u003e118(48.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50841750841751%\"\u003e\n \u003cp\u003e57.0\u0026plusmn;16.8\u003c/p\u003e\n \u003cp\u003e65(48.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.023569023569024%\"\u003e\n \u003cp\u003e51.2\u0026plusmn;17.3\u003c/p\u003e\n \u003cp\u003e53(48.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.993265993265993%\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe mean follow-up time in the Dabiga group was 49.5\u0026plusmn;23.4 months. Compared with dabigatran 110mg BID group, the proportion of long-term maintenance was lower in the dabigatran 110mg QD group (45.0% VS. 70.6%, P=0.008). There was no significant difference in follow-up outcomes between the other two groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe isogeneity test of survival analysis for bleeding events was performed between Dabigatran 110mg BID group and 110mg QD group, and the chi-square value of Log Rank was 0.180, P=0.671, with no statistical significance. Isogeneity test of survival analysis for thrombotic events was performed between Dabigatran 110mg BID group and 110mg QD group, and the Log Rank chi-square value was 0.021, P=0.886, with no statistical significance. The isogeneity test of survival analysis for death was performed between Dabigatran 110mg BID group and 110mg QD group, and the chi-square value of Log Rank was 2.594, P=0.107, with no statistical significance (Figure 2-4).\u003c/p\u003e\n\u003cp\u003eThe mean follow-up time of the rivaroxaban group was 32.1\u0026plusmn;20.1 months. The rivaroxaban 2.5mg BID group had a lower rate of long-term maintenance (61.6% VS. 79.9%, P=0.000) and a higher mortality rate (25.7% VS. 7.5%, P=0.001) than the rivaroxaban 5mg BID group. Non-cardiogenic mortality was higher (20.2% VS. 4.5%, P=0.000). There was no significant difference in follow-up outcomes between the other two groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the survival analysis distribution equality test for bleeding events between the rivaroxaban 5mg BID group and the 2.5mg BID group, the Log-Rank Chi-square value was 0.732, P=0.392, and the difference was not statistically significant. The distribution of survival analysis for thrombotic events in the rivaroxaban 5mg BID group and 2.5mg BID group was identical, and the Log-Rank Chi-square value was 0.615, P=0.433, with no statistical significance. The equivalence test of survival analysis for death between the rivaroxaban 5mg BID group and the 2.5mg BID group showed that the Log-Rank Chi-square value was 11.530, P=0.001, and the difference was not statistically significant (Figure 5-7).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe patients included in this study are the elderly population, more than half of them are over 80 years old, and the risk of bleeding and thrombosis is high, and there are more complications and combined drugs. Anticoagulant drugs and specific dosage plan are determined and adjusted by clinicians according to the general conditions and coagulation indexes of patients, which reflects the clinical reality of individualized anticoagulant therapy in elderly patients in China to a certain extent.\u003c/p\u003e \u003cp\u003eIn clinical work, the clinician adjusts the DOAC dose according to the patient's specific situation. Studies have shown that DOAC dose can be reduced in patients with the following clinical characteristics: elderly (\u0026ge;\u0026thinsp;75 years old), female, low weight (\u0026le;\u0026thinsp;60kg), renal insufficiency (CrCl\u0026thinsp;\u0026le;\u0026thinsp;50ml/min), previous bleeding history, combined history of hypertension, combined use of dronedarone or antiplatelet drugs, etc.\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e Studies have shown that Asian patients with low body weight, cancer, low baseline hemoglobin levels, prolonged prothrombin time, and low creatinine clearance are at increased risk of edoxaban related bleeding\u003csup\u003e[\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. This study found that the clinical characteristics of patients taking low-dose DOAC regimen included: age\u0026thinsp;\u0026ge;\u0026thinsp;80 years old, weight\u0026thinsp;\u0026le;\u0026thinsp;60kg, ADL score\u0026thinsp;\u0026le;\u0026thinsp;60 points, HAS-BLED score\u0026thinsp;\u0026ge;\u0026thinsp;3.0 points, eGFR\u0026thinsp;\u0026lt;\u0026thinsp;60ml/min/1.73m\u0026sup2;, and baseline hemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;120g/L.\u003c/p\u003e \u003cp\u003eIn this study, there was no difference in the survival analysis of bleeding events, thrombotic events, and death in the two dabigatran dose groups, and the incidence was lower than in previous studies. Both doses of rivaroxaban were not the recommended dose, and the incidence of major bleeding was 0% in the 5mg BID group and the 2.5mg BID group. 0%) and the incidence of thrombosis (2.2%; 2.7%) were lower than previous studies\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. The above results showed that in elderly people with high bleeding risk, the incidence of bleeding events did not increase and the incidence of thrombotic events decreased with the anticoagulation program formulated by individualized therapy, suggesting that there are clinical benefits of individualized DOAC therapy in elderly people.\u003c/p\u003e \u003cp\u003eIn this study, compared with the two doses of rivaroxaban, the 2.5mg BID group had a higher mortality rate (26.6% VS. 7.5%, P\u0026thinsp;=\u0026thinsp;0.000) and a higher non-cardiogenic mortality rate (20.2% VS. 4.5%, P\u0026thinsp;=\u0026thinsp;0.000). There was no significant difference in the incidence of bleeding events and thrombotic events. There was no difference in the survival analysis of bleeding events, thrombotic events and death in the rivaroxaban group. Although mortality was higher in the rivaroxaban 2.5mg BID group, survival analyses of death were not significantly different between the two groups, and the cause of death was more non-cardiogenic, which was considered to be associated with older patients enrolled in the 2.5mg BID group, worse general conditions, and more comorbidities.\u003c/p\u003e \u003cp\u003eIn this study, the correlation analysis between different doses and outcome events was limited by the number of enrolled cases and the influence of other clinical factors on outcome was not considered, which had certain limitations. The analysis could be further expanded after the sample size was adjusted for confounding factors.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe clinical characteristics of patients with individualized low-dose DOAC regimen were as follows: age\u0026thinsp;\u0026ge;\u0026thinsp;80 years old, weight\u0026thinsp;\u0026le;\u0026thinsp;60kg, ADL score\u0026thinsp;\u0026le;\u0026thinsp;60 points, HAS-BLED score\u0026thinsp;\u0026ge;\u0026thinsp;3 points, eGFR\u0026thinsp;\u0026lt;\u0026thinsp;60ml/min/1.73m\u0026sup2;, baseline hemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;120g/L. There was no significant difference in the incidence of bleeding and thrombotic events between individualized low-dose therapy based on patient clotting indicators and standard therapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthical Approval and Informed Consent to Participate\u003c/p\u003e\n\u003cp\u003ePatient’s identity is not disclosed anywhere, and informed consent has been obtained from all subjects and/or their legal guardians. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003eConsent for Publication\u003c/p\u003e\n\u003cp\u003eNot applicable for this segment.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eFunding information\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003eConflict of interest\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003eAuthors’ contributions\u003c/p\u003e\n\u003cp\u003eConception or design of the work: RZ; data collection: RZ; data analysis and interpretation: RZ; drafting the article: RZ; critical revision of the article: JD, ML; final approval of the version to be published: RZ, JD, ML\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eRose D K, Bar B, Direct Oral Anticoagulant Agents: Pharmacologic Profile, Indications, Coagulation Monitoring, and Reversal Agents [J], J Stroke Cerebrovasc Dis, 2018, 27(8): 2049-2058.\u003c/li\u003e\n \u003cli\u003eSrikajornlarp S, Amnueypol M, Vathesatogkit P, et al., Effectiveness and Safety of Direct Oral Anticoagulants in Thai Patients with Atrial Fibrillation: A Real-World Retrospective Cohort Study [J], Clin Appl Thromb Hemost, 2022, 28: 10760296221130058.\u003c/li\u003e\n \u003cli\u003eAlosaimi H M, Alqahtani S, Balkhi B, et al., A retrospective study of real-world effectiveness and safety of rivaroxaban in patients with non-valvular atrial fibrillation and venous thromboembolism in Saudi Arabia [J], PeerJ, 2022, 10: e13974.\u003c/li\u003e\n \u003cli\u003eDu X, Guo L, Xia S, et al., Atrial fibrillation prevalence, awareness and management in a nationwide survey of adults in China [J], Heart, 2021, 107(7): 535-541.\u003c/li\u003e\n \u003cli\u003eFukaya H, Oikawa J, Nakamura H, et al., Impact of different dose reduction criteria for anti-Xa direct oral anticoagulants on bleeding complications: A single center observational study [J], J Arrhythm, 2022, 38(3): 386-394.\u003c/li\u003e\n \u003cli\u003eSugrue A, Sanborn D, Amin M, et al., Inappropriate Dosing of Direct Oral Anticoagulants in Patients with Atrial Fibrillation [J], Am J Cardiol, 2021, 144: 52-59.\u003c/li\u003e\n \u003cli\u003eWarkentin L, Hueber S, Deiters B, et al., Vitamin-K-antagonist phenprocoumon versus low-dose direct oral anticoagulants (DOACs) in patients with atrial fibrillation: a real-world analysis of German claims data [J], Thromb J, 2022, 20(1): 31.\u003c/li\u003e\n \u003cli\u003eWheelock K M, Ross J S, Murugiah K, et al., Clinician Trends in Prescribing Direct Oral Anticoagulants for US Medicare Beneficiaries [J], JAMA Netw Open, 2021, 4(12): e2137288.\u003c/li\u003e\n \u003cli\u003eKvasnicka T, Malikova I, Zenahlikova Z, et al., Rivaroxaban - Metabolism, Pharmacologic Properties and Drug Interactions [J], Curr Drug Metab, 2017, 18(7): 636-642.\u003c/li\u003e\n \u003cli\u003eZhang H, Liu Z, Mu G, et al., Diagnostic performance of coagulation indices for direct oral anticoagulant concentration [J], Thromb Res, 2020, 195: 171-179.\u003c/li\u003e\n \u003cli\u003eLee S R, Lee Y S, Park J S, et al., Label Adherence for Non-Vitamin K Antagonist Oral Anticoagulants in a Prospective Cohort of Asian Patients with Atrial Fibrillation [J], Yonsei Med J, 2019, 60(3): 277-284.\u003c/li\u003e\n \u003cli\u003eMikami T, Hirabayashi K, Okawa K, et al., Laboratory Test Predictors for Major Bleeding in Elderly (\u0026ge;80\u0026thinsp;Years) Patients With Nonvalvular Atrial Fibrillation Treated With Edoxaban 15\u0026thinsp;mg: Sub-Analysis of the ELDERCARE-AF Trial [J], Journal of the American Heart Association, 2022, 11(17): e024970.\u003c/li\u003e\n \u003cli\u003eLee O S, Kim W, Jang B M, et al., Association of risk factors and bleeding complications in Asian patients taking edoxaban [J], Br J Clin Pharmacol, 2021, 87(4): 2121-2127.\u003c/li\u003e\n \u003cli\u003eTakase T, Ikesue H, Nakagawa H, et al., Risk Factors for Major Bleeding and Clinically Relevant Non-major Bleeding in Japanese Patients Treated with Edoxaban [J], Biol Pharm Bull, 2020, 43(3): 458-462.\u003c/li\u003e\n \u003cli\u003eHalperin J L, Hankey G J, Wojdyla D M, et al., Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) [J], Circulation, 2014, 130(2): 138-146.\u003c/li\u003e\n\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":"Direct oral anticoagulant, Dabigatran, Rivaroxaban, Anti-factor Xa activity, Aged","lastPublishedDoi":"10.21203/rs.3.rs-3800887/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3800887/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction:\u003c/strong\u003e It is common to adjust direct oral anticoagulant (DOAC) dosage individually according to the clinical characteristics and coagulation indexes of patients in clinical practice, but its effectiveness and safety are still controversial. The purpose of this study was to analyze the clinical characteristics and follow-up outcomes of elderly patients who adjusted anticoagulant therapy according to coagulation index.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e Included were patients who were admitted to the geriatric Department of Peking University First Hospital from January 1, 2016 to December 31, 2021, with indications of anticoagulation therapy, receiving DOAC (Dabigatran, Rivaroxaban) therapy, individualized dose adjustment according to APTT (peak value of 46-60s) or AXA (peak value of 0.5-1.0IU/ml), aged ≥60 years, and complete clinical data. Outpatient or telephone follow-up every three months after discharge until termination or death or end of study (December 31, 2022). The clinical features and follow-up results of Dabigatran 110mg BID group and Dabigatran 110mg QD group, Rivaroxaban 5mg BID group and Rivaroxaban 2.5mg BID group were compared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult: \u003c/strong\u003eA total of 388 patients were enrolled, including 145 (35.1%) in the Dabigatrangroup and 243 (58.8%) in the rivaroxaban group. The Dabigatrangroup was divided into the 110mg BID group (85 cases) and the 110mg QD group (60 cases), and patients in the 110mg QD group were older, lighter, and had lower glomerular filtration rate (eGFR). The Rivaroxaban group was divided into the 5mg BID group (134 cases) and the 2.5mg BID group (109 cases), and patients in the 2.5mg BID group were older, weighed less, had lower activity of daily living (ADL) scores, and had lower eGFR. The mean follow-up time was 49.5±23.4 months in the Dabigatrangroup and 32.1±20.1 months in the Rivaroxaban group. Survival analysis of bleeding events, thrombotic events, and death was not significantly different between Dabigatran 110mgBID and 110mgQD and Rivaroxaban 5mgBID and 2.5mgBID groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The clinical characteristics of patients with individualized low-dose DOAC regimen were as follows: age ≥80 years old, weight ≤60kg, ADL score ≤60 points, HAS-BLED score ≥3 points, eGFR \u0026lt; 60ml/min/1.73m², baseline hemoglobin \u0026lt; 120g/L. There was no significant difference in the incidence of bleeding and thrombotic events between individualized low-dose therapy based on patient clotting indicators and standard therapy.\u003c/p\u003e","manuscriptTitle":"Clinical Features and Follow-up Outcomes of Individualized Low-dose DOAC Therapy in Chinese Patients Aged 60 Years and Older: A Single-center Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-02 17:17:21","doi":"10.21203/rs.3.rs-3800887/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":"ebb40d22-789d-4d2d-af36-ba1493a5b882","owner":[],"postedDate":"January 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-05T06:29:44+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-02 17:17:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3800887","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3800887","identity":"rs-3800887","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}