Chen Can, Kan Yuanqing, Shi Zhenyu, Guo Daqiao, Fu Weiguo, Li Yanli, Lv Qianzhou, Li Xiaoyu, Si Yi
Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Front Pharmacol. 2021 Feb 8;11:608247. doi: 10.3389/fphar.2020.608247. eCollection 2020.
This study aims to explore the role of low-dose rivaroxaban (≤10 mg daily) for the treatment of atherosclerotic cardiovascular disease (ASCVD). PubMed, Embase and the Cochrane Library were searched for randomized controlled trials (RCTs) of low-dose rivaroxaban in patients with ASCVD including coronary artery disease (CAD) and peripheral artery disease (PAD). Literature screening, data extraction, and risk of bias assessment were carried out independently by two researchers. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using random-effect models to determine risks of outcomes in ASCVD patients treated with rivaroxaban and comparators, and meta-analysis was conducted via Review Manager 5.3.5 software. 3,768 records were obtained through literature search, and 9 articles representing 6 RCTs ultimately qualified for this study. The meta-analysis indicated that for patients with CAD, the addition of rivaroxaban (5 mg daily) to aspirin could significantly reduce the risk of major adverse cardiovascular events (MACEs) compared with aspirin alone (HR 0.81, 95% CI, 0.72 to 0.91, = 0.0004, I = 60%, 4 studies). For PAD patients receiving rivaroxaban (5 mg daily) plus aspirin, there was no significant reduction in the risk of MACEs (HR 0.84, 95% CI, 0.63 to 1.13, = 0.25, I = 74%, 2 studies); however, there was significant reduction in major adverse limb events (MALEs) (HR 0.54, 95% CI, 0.35 to 0.83, = 0.005, one studies) and in the composite of MACEs or MALEs (HR 0.78, 95% CI, 0.64 to 0.95, = 0.02, I = 66%, 2 studies) when compared with patients receiving aspirin alone. Meanwhile, rivaroxaban combined with aspirin significantly increased the risk of International Society on Thrombosis and Haemostasis (ISTH) major bleeding compared with aspirin alone in patients with CAD (HR 1.74, 95% CI, 1.43 to 2.13, < 0.00001, I = 0%, 2 studies) and PAD (HR 1.47, 95% CI, 1.19 to 1.83, = 0.0004, I = 0%, 2 studies). Compared with standard antiplatelet therapy, the addition of a 5 mg daily dose of rivaroxaban to standard antiplatelet therapy may improve cardiovascular or limb outcomes of patients with ASCVD, with an increase in major bleeding. Patients who would benefit from the addition of low-dose rivaroxaban to antiplatelet agents and appropriate dual-pathway antithrombotic strategies should be identified in clinical practice to individualize antithrombotic therapy.
本研究旨在探讨低剂量利伐沙班（每日≤10毫克）在治疗动脉粥样硬化性心血管疾病（ASCVD）中的作用。检索了PubMed、Embase和Cochrane图书馆，以查找低剂量利伐沙班用于ASCVD患者（包括冠状动脉疾病（CAD）和外周动脉疾病（PAD））的随机对照试验（RCT）。由两名研究人员独立进行文献筛选、数据提取和偏倚风险评估。使用随机效应模型计算风险比（HR）和95%置信区间（CI），以确定接受利伐沙班和对照药物治疗的ASCVD患者的结局风险，并通过Review Manager 5.3.5软件进行荟萃分析。通过文献检索获得3768条记录，最终有9篇文章代表6项RCT符合本研究要求。荟萃分析表明，对于CAD患者，与单独使用阿司匹林相比，在阿司匹林基础上加用利伐沙班（每日5毫克）可显著降低主要不良心血管事件（MACE）的风险（HR 0.81，95% CI，0.72至0.91，P = 0.0004，I² = 60%，4项研究）。对于接受利伐沙班（每日5毫克）加阿司匹林治疗的PAD患者，MACE风险没有显著降低（HR 0.84，95% CI，0.63至1.13，P = 0.25，I² = 74%，2项研究）；然而，与单独接受阿司匹林治疗的患者相比，主要不良肢体事件（MALE）风险显著降低（HR 0.54，95% CI，0.35至0.83，P = 0.005，1项研究），MACE或MALE复合结局风险也显著降低（HR 0.78，95% CI，0.64至0.95，P = 0.02，I² = 66%，2项研究）。同时，与单独使用阿司匹林相比，利伐沙班联合阿司匹林在CAD患者（HR 1.74，95% CI，1.43至2.13，P < 0.00001，I² = 0%，2项研究）和PAD患者（HR 1.47，95% CI，1.19至1.83，P = 0.0004，I² = 0%，2项研究）中显著增加了国际血栓与止血学会（ISTH）严重出血的风险。与标准抗血小板治疗相比，在标准抗血小板治疗基础上加用每日5毫克利伐沙班可能改善ASCVD患者的心血管或肢体结局，但会增加严重出血风险。在临床实践中应确定哪些患者可从在抗血小板药物中加用低剂量利伐沙班及适当的双途径抗栓策略中获益，以实现抗栓治疗的个体化。
