Dabigatran Etexilate and Risk of Myocardial Infarction, Other Cardiovascular Events, Major Bleeding, and All‐Cause Mortality: A Systematic Review and Meta‐analysis of Randomized Controlled Trials

Abstract

Background Signals of an increased risk of myocardial infarction ( MI ) have been identified with dabigatran etexilate in randomized controlled trials ( RCTs ). Methods and Resules We conducted searches of the published literature and a clinical trials registry maintained by the drug manufacturer. Criteria for inclusion in our meta‐analysis included all RCT s and the availability of outcome data for MI , other cardiovascular events, major bleeding, and all‐cause mortality. Among the 501 unique references identified, 14 RCT s fulfilled the inclusion criteria. Stratification analyses by comparators and doses of dabigatran etexilate were conducted. Peto odds ratio ( OR PETO ) values using the fixed‐effect model ( FEM ) for MI , other cardiovascular events, major bleeding, and all‐cause mortality were 1.34 (95% CI 1.08 to 1.65, P =0.007), 0.93 (95% CI 0.83 to 1.06, P =0.270), 0.88 (95% CI 0.79 to 0.99, P =0.029), and 0.89 (95% CI 0.80 to 1.00, P =0.041). When compared with warfarin, OR PETO values using FEM were 1.41 (95% CI 1.11 to 1.80, P =0.005), 0.94 (95% CI 0.83 to 1.06, P =0.293), 0.85 (95% CI 0.76 to 0.96, P =0.007), and 0.90 (95% CI 0.81 to 1.01, P =0.061), respectively. In RCT s using the 150‐mg BID dosage, the OR PETO values using FEM were 1.45 (95% CI 1.11 to 1.91, P =0.007), 0.95 (95% CI 0.82 to 1.09, P =0.423), 0.92 (95% CI 0.81 to 1.05, P =0.228), and 0.88 (95% CI 0.78 to 1.00, P =0.045), respectively. The results of the 110‐mg BID dosage were mainly driven by the RE ‐ LY trial. Conclusions This meta‐analysis provides evidence that dabigatran etexilate is associated with a significantly increased risk of MI . This increased risk should be considered taking into account the overall benefit in terms of major bleeding and all‐cause mortality.