Abstract 15500: Dabigatran is Associated with Higher Risk of Myocardial Infarction or Acute Coronary Syndromes: a Meta-analysis of Non-Inferiority Randomized Controlled Trials
Introduction: The original RE-LY trial suggested a small increased risk of myocardial infarction (MI) with the use of dabigatran vs. warfarin in atrial fibrillation (Afib) patients. We systematically evaluated the risk of MI or acute coronary syndrome (ACS) with the use of dabigatran for several clinical indications and against different controls.
Methods: We searched in Pubmed non-inferiority randomized controlled trials evaluating the efficacy of dabigatran that reported MI or ACS as secondary outcomes. Due to scarcity of outcomes, we performed a meta-analysis with the fixed effects Mantel-Haenzel (M-H) method to evaluate the effect of dabigatran on MI or ACS. We expressed the associations as Odds Ratios (OR) and their 95% Confidence Intervals (CI). Heterogeneity of effect among trials was tested with the Q test and quantified with the I2. Other measures of association (Risk ratios, Risk Differences) and other methods (Peto, Inverse Variance, Random Effects) were also used. Analyses were repeated after excluding the short follow-up (≤1month) trials, as harmful effects of dabigatran may be higher with long-term use.
Results: Seven trials were selected (n=31097), including two studies of stroke prophylaxis in AFib, one in acute venous thomboembolism, one in ACS patients, and three of short-term prophylaxis of deep venous thrombosis. The control arms included warfarin, enoxaparin or placebo. Dabigatran was significantly associated with a higher risk for MI or ACS than the control group (Dabigatran 255/20718 [1.23%] vs. Control 91/10379 [0.88%], ORM-H 1.31, 95%CI 1.03-1.67, p=0.03). The risk for MI or ACS was similar when using revised RE-LY trial results (ORM-H 1.25, 95%CI 1.00-1.57, p=0.05). When excluding the short-term trials, the risk of MI or ACS was similar and significant (ORM-H 1.33, 95%CI 1.03-1.72, p=0.03). Risks were not heterogeneous for all analyses (I2=0%, p>0.4), and consistent when using different methods and measures of association.
Conclusions: Dabigatran is associated with an increased risk of MI or ACS in a broad spectrum of patients and when tested against different controls. Patients and providers should consider the potential of these serious harmful cardiovascular effects of dabigatran.
- © 2011 by American Heart Association, Inc.