Comparative coronary risks of apixaban, rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison

Br J Clin Pharmacol. 2014 Oct;78(4):707-17. doi: 10.1111/bcp.12376.

Abstract

Aims: There are concerns regarding increased risk of acute coronary syndrome with dabigatran. We aimed to assess whether alternative treatment options such as rivaroxaban or apixaban carry a similar risk as compared with dabigatran.

Methods: We searched MEDLINE and EMBASE for randomized controlled trials of apixaban, dabigatran or rivaroxaban against control (placebo, heparin or vitamin K antagonist). We pooled odds ratios (OR) for adverse coronary events (acute coronary syndrome or myocardial infarction) using fixed effect meta-analysis and assessed heterogeneity with I(2) . We conducted adjusted indirect comparisons to compare risk of adverse coronary events with apixaban or rivaroxaban vs. dabigatran.

Results: Twenty-seven randomized controlled trials met the inclusion criteria. Dabigatran was associated with a significantly increased risk of adverse coronary events in pooled analysis of nine trials (OR 1.45, 95% CI 1.14, 1.86). There was no signal for coronary risk with apixaban from nine trials (pooled OR 0.89, 95% CI 0.78, 1.03) or rivaroxaban from nine trials (pooled OR 0.81, 95% CI 0.72, 0.93). Overall, adjusted indirect comparison suggested that both apixaban (OR 0.61, 95% CI 0.44, 0.85) and rivaroxaban (OR 0.54; 95% CI 0.39, 0.76) were associated with lower coronary risk than dabigatran. Restricting the indirect comparison to a vitamin K antagonist as a common control, yielded similar findings, OR 0.57 (95% CI 0.39, 0.85) for apixaban vs. dabigatran and 0.53 (95% CI 0.37, 0.77) for rivaroxaban vs. dabigatran.

Conclusions: There are significant differences in the comparative safety of apixaban, rivaroxaban and dabigatran with regards to acute coronary adverse events.

Keywords: acute coronary syndrome; apixaban; dabigatran; rivaroxaban.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Acute Coronary Syndrome / chemically induced*
  • Antithrombins / adverse effects*
  • Benzimidazoles / adverse effects*
  • Dabigatran
  • Factor Xa Inhibitors / adverse effects*
  • Humans
  • Morpholines / adverse effects*
  • Pyrazoles / adverse effects*
  • Pyridones / adverse effects*
  • Randomized Controlled Trials as Topic
  • Rivaroxaban
  • Thiophenes / adverse effects*
  • beta-Alanine / adverse effects
  • beta-Alanine / analogs & derivatives*

Substances

  • Antithrombins
  • Benzimidazoles
  • Factor Xa Inhibitors
  • Morpholines
  • Pyrazoles
  • Pyridones
  • Thiophenes
  • beta-Alanine
  • apixaban
  • Rivaroxaban
  • Dabigatran