Department of Cardiovascular Medicine, Ningbo Hwamei Hospital, University of Chinese Academy of Sciences, No. 41, Northwest Street, Haishu District, Ningbo City, 315000, Zhejiang Province, China.
School of Health, Brooks College (Sunnyvale), Milpitas, CA, USA.
Am J Cardiovasc Drugs. 2023 May;23(3):257-267. doi: 10.1007/s40256-023-00574-9. Epub 2023 Mar 3.
The aim of this study was to evaluate the efficacy and safety of antithrombotic regimens and their combinations in preventing thrombotic incidents in patients with stable atherosclerotic cardiovascular disease (S-ASCVD).
A systematic literature search was conducted in the PubMed, Embase, Cochrane Library, Scopus, and Google Scholar databases. The primary comprehensive endpoint was a major adverse cardiovascular event (MACE) composite of cardiovascular death, stroke, or myocardial infarction, while the secondary endpoints were cardiovascular death, all-cause stroke, ischemic stroke, myocardial infarction, and all-cause death. The safety endpoint was major bleeding. Bayesian network meta-regression analysis in R software was used to calculate the final effect size and to correct for the effect of follow-up time on the outcome effect size.
Twelve studies reporting 122,190 patients with eight antithrombotic regimens were included in this systematic review. For the primary composite endpoint, low-dose aspirin plus clopidogrel 75 mg (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.33-0.87) and low-dose aspirin plus rivaroxaban 2.5 mg twice daily (HR 0.53, 95% CI 0.34-0.82) showed significantly better efficacy than clopidogrel monotherapy, and the efficacy was comparable among the first two regimens. Unfortunately, none of the active regimens significantly decreased all-cause death, cardiovascular death branch, and all-cause stroke as part of the secondary endpoints. Low-dose aspirin plus ticagrelor 90 mg twice daily (HR 0.81, 95% CI 0.69-0.94) and low-dose aspirin plus ticagrelor 60 mg twice daily (HR 0.84, 95% CI 0.74-0.95) had a significant advantage in myocardial infarction compared with low-dose aspirin monotherapy, while low-dose aspirin plus 2.5 mg rivaroxaban twice daily (HR 0.62, 95% CI 0.41-0.94) was better than low-dose aspirin in the treatment of ischemic stroke. In the major bleeding branch, low-dose aspirin plus ticagrelor 90 mg twice daily (HR 2.2, 95% CI 1.70-2.90), low-dose aspirin plus ticagrelor 60 mg twice daily (HR 2.1, 95% CI 1.70-2.60), low-dose aspirin plus rivaroxaban 2.5 mg twice daily (HR 1.7, 95% CI 1.30-2.00), and rivaroxaban 5 mg twice daily (HR 1.5, 95% CI 1.20-1.90) showed higher major bleeding risk compared with low-dose aspirin.
Considering MACEs, myocardial infarction, all kinds of stroke, ischemic stroke, and major bleeding, low-dose aspirin plus rivaroxaban 2.5 mg twice daily should be considered the preferred regimen for S-ASCVD patients with low bleeding risk.
本研究旨在评估抗栓治疗方案及其组合在预防稳定型动脉粥样硬化性心血管疾病（S-ASCVD）患者血栓事件中的疗效和安全性。
在 PubMed、Embase、Cochrane 图书馆、Scopus 和 Google Scholar 数据库中进行系统文献检索。主要综合终点为心血管死亡、卒中和心肌梗死组成的主要不良心血管事件（MACE）复合终点，次要终点为心血管死亡、全因卒中和缺血性卒中和全因死亡。安全性终点为大出血。采用 R 软件中的贝叶斯网络荟萃回归分析计算最终效应大小，并校正随访时间对结局效应大小的影响。
本系统评价纳入了 12 项研究，共 122190 例患者，涉及 8 种抗栓治疗方案。对于主要复合终点，小剂量阿司匹林加氯吡格雷 75mg（HR 0.53，95%置信区间 [CI] 0.33-0.87）和小剂量阿司匹林加利伐沙班 2.5mg 每日两次（HR 0.53，95%CI 0.34-0.82）的疗效明显优于氯吡格雷单药治疗，且前两种方案的疗效相当。遗憾的是，没有一种活性方案能显著降低次要终点的全因死亡、心血管死亡和全因卒中等。小剂量阿司匹林加替格瑞洛 90mg 每日两次（HR 0.81，95%CI 0.69-0.94）和小剂量阿司匹林加替格瑞洛 60mg 每日两次（HR 0.84，95%CI 0.74-0.95）在心肌梗死方面优于小剂量阿司匹林单药治疗，而小剂量阿司匹林加 2.5mg 每日两次利伐沙班（HR 0.62，95%CI 0.41-0.94）在治疗缺血性卒中有优势。在大出血方面，小剂量阿司匹林加替格瑞洛 90mg 每日两次（HR 2.2，95%CI 1.70-2.90）、小剂量阿司匹林加替格瑞洛 60mg 每日两次（HR 2.1，95%CI 1.70-2.60）、小剂量阿司匹林加利伐沙班 2.5mg 每日两次（HR 1.7，95%CI 1.30-2.00）和利伐沙班 5mg 每日两次（HR 1.5，95%CI 1.20-1.90）与小剂量阿司匹林相比，大出血风险更高。
考虑到 MACE、心肌梗死、各种卒中和缺血性卒中和大出血，对于低出血风险的 S-ASCVD 患者，小剂量阿司匹林加利伐沙班 2.5mg 每日两次应作为首选方案。
