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- Title
Effect of Rivaroxaban vs Enoxaparin on Major Cardiac Adverse Events and Bleeding Risk in the Acute Phase of Acute Coronary Syndrome: The H-REPLACE Randomized Equivalence and Noninferiority Trial.
- Authors
Zhou, Shenghua; Xiao, Yichao; Zhou, Chonglun; Zheng, Zhaofen; Jiang, Weihong; Shen, Qiang; Zhu, Can; Pan, Hongwei; Liu, Changhui; Zeng, Gaofeng; Ge, Liangqing; Zhang, Yumin; Ouyang, Zewei; Fu, Guang; Pan, Gang; Chen, Feng; Huang, Lihong; Liu, Qiming
- Abstract
Key Points: Question: Is short-term oral rivaroxaban a noninferior alternative to parenteral enoxaparin in the acute phase of acute coronary syndrome (ACS)? Findings: This equivalence and noninferiority trial including 2046 patients found that short-term rivaroxaban 5 mg twice daily was noninferior to enoxaparin in terms of bleeding risk and efficacy in reducing major adverse cardiovascular events during 6 months of follow-up among patients with ACS who missed the primary reperfusion window and before selective revascularization. Meaning: These findings suggest that rivaroxaban-5 mg twice daily may be a reasonable alternative to enoxaparin in the acute phase of ACS, which may provide useful information for designing future definitive randomized clinical trials with sufficient sample sizes. This randomized equivalence and noninferiority trial compares safety and efficacy of enoxaparin vs rivaroxaban 2.5 or 5 mg for patients with acute coronary syndrome (ACS) in the acute phase. Importance: Parenteral enoxaparin is a preferred anticoagulant used in the acute phase for patients with acute coronary syndrome (ACS). The safety and efficacy of short-term low-dose rivaroxaban in this clinical setting remain unknown. Objective: To compare the safety and efficacy of rivaroxaban vs enoxaparin in the acute phase of ACS. Design, Setting, and Participants: This multicenter, prospective, open-label, active-controlled, equivalence and noninferiority trial was conducted from January 2017 through May 2021 with a 6-month follow-up at 21 hospitals in China. Participants included patients with ACS missing the primary reperfusion window or before selective revascularization. Data were analyzed from November 2021 to November 2022. Interventions: Participants were randomized 1:1:1 to oral rivaroxaban 2.5 mg or 5 mg or 1 mg/kg subcutaneous enoxaparin twice daily in addition to dual antiplatelet therapy (DAPT; aspirin 100 mg and clopidogrel 75 mg once daily) for a mean of 3.7 days. Main Outcomes and Measures: The primary safety end point was bleeding events, as defined by the International Society on Thrombosis and Haemostasis, and the primary efficacy end point was major adverse cardiovascular events (MACEs), including cardiac death, myocardial infarction, rerevascularization, or stroke during the 6-month follow-up. Results: Of 2055 enrolled patients, 2046 (99.6%) completed the trial (mean [SD] age 65.8 [8.2] years, 1443 [70.5%] male) and were randomized to enoxaparin (680 patients), rivaroxaban 2.5 mg (683 patients), or rivaroxaban 5 mg (683 patients). Bleeding rates were 46 patients (6.8%) in the enoxaparin group, 32 patients (4.7%) in the rivaroxaban 2.5 mg group, and 36 patients (5.3%)in the rivaroxaban 5 mg group (rivaroxaban 2.5 mg vs enoxaparin: noninferiority hazard ratio [HR], 0.68; 95% CI, 0.43 to 1.07; P =.005; rivaroxaban 5 mg vs enoxaparin: noninferiority HR, 0.88; 95% CI, 0.70 to 1.09; P =.001). The incidence of MACEs was similar among groups, and noninferiority was reached in the rivaroxaban 5 mg group (HR, 0.60; 95% CI, 0.31 to 1.16, P =.02) but not in the rivaroxaban 2.5 mg group (HR, 0.68; 95% CI, 0.36 to 1.30; P =.05) compared with the enoxaparin group. Conclusions and Relevance: In this equivalence and noninferiority trial, oral rivaroxaban 5 mg showed noninferiority to subcutaneous enoxaparin (1 mg/kg) for patients with ACS treated with DAPT during the acute phase. Results of this feasibility study provide useful information for designing future randomized clinical trials with sufficient sample sizes. Trial Registration: ClinicalTrials.gov Identifier: NCT03363035
- Subjects
CHINA; MORTALITY risk factors; HEMORRHAGE prevention; STROKE risk factors; ENOXAPARIN; DRUG efficacy; RESEARCH; PILOT projects; CLINICAL trials; CONFIDENCE intervals; MYOCARDIAL reperfusion; COMBINATION drug therapy; MAJOR adverse cardiovascular events; REVASCULARIZATION (Surgery); SELF-evaluation; ACUTE coronary syndrome; PATIENT readmissions; RACE; RIVAROXABAN; ST elevation myocardial infarction; RANDOMIZED controlled trials; LOW-molecular-weight heparin; CRITICAL care medicine; DESCRIPTIVE statistics; SURVIVAL analysis (Biometry); KAPLAN-Meier estimator; PLATELET aggregation inhibitors; RESEARCH funding; DATA analysis software; STATISTICAL sampling; LONGITUDINAL method; PROPORTIONAL hazards models; PATIENT safety; EVALUATION
- Publication
JAMA Network Open, 2023, Vol 6, Issue 2, pe2255709
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2022.55709