PubMed, Scopus, and the Web of Science were searched for randomized controlled trials of dabigatran that reported on MI or ACS as secondary outcomes. The fixed-effects Mantel-Haenszel (M-H) test was used to evaluate the effect of dabigatran on MI or ACS. Associations were expressed as odds ratios (ORs) and their 95% CIs.Seven trials were selected (N = 30 514), including 2 studies of stroke prophylaxis in atrial fibrillation, 1 in acute venous thromboembolism, 1 in ACS, and 3 of short-term prophylaxis of deep venous thrombosis. Control arms included warfarin, enoxaparin, or placebo administration.
Dabigatran was significantly associated with a higher risk of MI or ACS than that seen with agents used in the control group (dabigatran, 237 of 20 000 [1.19%] vs control, 83 of 10 514 [0.79%]; ORM-H, 1.33; 95% CI, 1.03-1.71; P = .03). The risk of MI or ACS was similar when using revised RE-LY trial results (ORM-H, 1.27; 95% CI, 1.00-1.61; P = .05) or after exclusion of short-term trials (ORM-H, 1.33; 95% CI, 1.03-1.72; P = .03). Risks were not heterogeneous for all analyses (I2 = 0%; P .30) and were consistent using different methods and measures of association.
The authors conclude that dabigatran is associated with an increased risk of MI or ACS in a broad spectrum of patients when tested against different controls.
In an accompanying comment (2), the journal editor states that continued data collection and analysis ‘allows to learn important additional information about new drugs after US Food and Drug Administration approval and highlight the importance of continued collection and analysis of data after drug approval’.
1. Ken Uchino, MD; Adrian V. Hernandez, MD, PhD. Dabigatran Association With Higher Risk of Acute Coronary Events. Meta-analysis of Noninferiority Randomized Controlled Trials. Arch Intern Med. 2012;172(5):397-402.
2. Rita F. Redberg, MD. Important Data After Drug Approval. Comment on "Dabigatran Association With Higher Risk of Acute Coronary Events". Arch Intern Med. 2012;172(5):404.