Division of Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Quebec, Canada.
Am J Cardiol. 2013 Aug 1;112(3):454-60. doi: 10.1016/j.amjcard.2013.03.054. Epub 2013 May 1.
Rivaroxaban, a factor Xa inhibitor, is a new oral anticoagulant that has been developed as an alternative to vitamin K antagonists. However, its safety remains unclear. Reported randomized controlled trials comparing the safety of rivaroxaban with that of vitamin K antagonists (warfarin, acenocoumarol, phenprocoumon, and fluindione) were systematically searched. Inclusion was restricted to studies of ≥30 days' treatment duration. Safety end points examined included major and clinically relevant nonmajor bleeding, as well as mortality. Data were pooled across randomized controlled trials using random-effects meta-analysis models. Five randomized controlled trials including 23,063 patients that met the inclusion criteria were identified. Patients received treatment for nonvalvular atrial fibrillation (n = 14,264), deep vein thrombosis (n = 3,967), or acute symptomatic pulmonary embolism (n = 4,832). Overall, rivaroxaban was not associated with the risk of a composite end point of major or clinically relevant nonmajor bleeding (relative risk 0.99, 95% confidence interval 0.93 to 1.06). However, rivaroxaban was associated with a significant decrease in fatal bleeding (relative risk 0.48, 95% confidence interval 0.31 to 0.74). In 2 studies reporting intracranial bleeding events, rivaroxaban was associated with decreased risk compared with vitamin K antagonists. It was not associated with decreased risk for all-cause mortality (relative risk 0.89, 95% confidence interval 0.73 to 1.09). In conclusion, with a decrease in fatal bleeding and no suggestion of an increase in all-cause mortality, rivaroxaban has a favorable safety profile with respect to bleeding.
利伐沙班是一种新型的 Xa 因子抑制剂，是作为维生素 K 拮抗剂的替代物而开发的。然而，其安全性仍不清楚。系统检索了比较利伐沙班与维生素 K 拮抗剂（华法林、醋硝香豆素、苯丙香豆素和双香豆素）安全性的随机对照试验。纳入研究仅限于治疗持续时间≥30 天的研究。检查的安全性终点包括主要和临床相关的非主要出血以及死亡率。使用随机效应荟萃分析模型对随机对照试验的数据进行汇总。确定了 5 项符合纳入标准的包括 23063 例患者的随机对照试验。患者接受非瓣膜性心房颤动（n=14264）、深静脉血栓形成（n=3967）或急性有症状的肺栓塞（n=4832）的治疗。总体而言，利伐沙班与主要或临床相关的非主要出血复合终点风险无关（相对风险 0.99，95%置信区间 0.93 至 1.06）。然而，利伐沙班与致命性出血显著减少相关（相对风险 0.48，95%置信区间 0.31 至 0.74）。在 2 项报告颅内出血事件的研究中，与维生素 K 拮抗剂相比，利伐沙班与降低风险相关。它与全因死亡率降低无关（相对风险 0.89，95%置信区间 0.73 至 1.09）。总之，利伐沙班在致命性出血减少的情况下没有提示全因死亡率降低，其在出血方面具有有利的安全性特征。
