Meta-analysis of rivaroxaban and bleeding risk

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.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cause of Death
  • Hemorrhage / chemically induced*
  • Hemorrhage / mortality
  • Humans
  • Morpholines / adverse effects*
  • Morpholines / therapeutic use
  • Randomized Controlled Trials as Topic
  • Risk
  • Rivaroxaban
  • Thiophenes / adverse effects*
  • Thiophenes / therapeutic use
  • Vitamin K / antagonists & inhibitors


  • Morpholines
  • Thiophenes
  • Vitamin K
  • Rivaroxaban