A meta-analysis of randomized controlled trials of the risk of bleeding with apixaban versus vitamin K antagonists

Am J Cardiol. 2015 Feb 15;115(4):533-41. doi: 10.1016/j.amjcard.2014.11.039. Epub 2014 Dec 2.

Abstract

Apixaban is one of the new oral anticoagulants, which is prescribed as an alternative to vitamin K antagonists (VKAs). Concerns regarding its bleeding profile persist and require further evaluation. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to compare the risks of bleeding and all-cause mortality between apixaban and VKAs. The MEDLINE, EMBASE, and Cochrane Library of Clinical Trials databases were systematically searched for RCTs comparing the risks of bleeding and all-cause mortality of apixaban (2.5 or 5 mg twice daily) with those of VKAs. We included RCTs conducted in adults and published in English or French. Data were pooled across RCTs using random-effects meta-analytical models. Our systematic search identified 5 RCTs meeting our inclusion criteria (n = 24,435). They included patients with atrial fibrillation (n = 18,358), total knee replacement surgery (n = 458), and venous thromboembolism (n = 5,619). Data pooled across RCTs revealed that apixaban was associated with reduced risks of any bleeding (relative risk [RR] 0.73, 95% confidence interval [CI] 0.59 to 0.90) and a composite of major or clinically relevant nonmajor bleeding (RR 0.60, 95% CI 0.40 to 0.88). Apixaban was also associated with a lower risk of intracranial bleeding (RR 0.42, 95% CI 0.31 to 0.58) whereas analyses of major and minor bleeding were inconclusive. Moreover, apixaban was associated with decreased all-cause mortality (RR 0.89, 95% CI 0.81 to 0.99) although this finding was driven by the results of the ARISTOTLE trial. In conclusion, our meta-analysis found that apixaban is associated with a lower risk of bleeding than VKAs, providing some reassurance regarding its safety.

Publication types

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

MeSH terms

  • Anticoagulants / adverse effects*
  • Anticoagulants / therapeutic use
  • Factor Xa Inhibitors / adverse effects
  • Factor Xa Inhibitors / therapeutic use
  • Global Health
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology*
  • Humans
  • Incidence
  • Pyrazoles / adverse effects*
  • Pyrazoles / therapeutic use
  • Pyridones / adverse effects*
  • Pyridones / therapeutic use
  • Randomized Controlled Trials as Topic*
  • Risk Factors
  • Venous Thromboembolism / prevention & control*
  • Vitamin K / antagonists & inhibitors*

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • Vitamin K
  • apixaban