Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials.
BACKGROUND
The original RE-LY (Randomized Evaluation of Long-term Anticoagulant Therapy) trial suggested a small increased risk of myocardial infarction (MI) with the use of dabigatran etexilate vs warfarin in patients with atrial fibrillation. We systematically evaluated the risk of MI or acute coronary syndrome (ACS) with the use of dabigatran.


METHODS
We searched PubMed, Scopus, and the Web of Science 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. We expressed the associations as odds ratios (ORs) and their 95% CIs.


RESULTS
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%]; OR(M-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 (OR(M-H), 1.27; 95% CI, 1.00-1.61; P = .05) or after exclusion of short-term trials (OR(M-H), 1.33; 95% CI, 1.03-1.72; P = .03). Risks were not heterogeneous for all analyses (I(2) = 0%; P ≥ .30) and were consistent 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 when tested against different controls. Clinicians should consider the potential of these serious harmful cardiovascular effects with use of dabigatran.
Cerebrovascular Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, Mail Code S80, Cleveland, OH 44195, USA. uchinok@ccf.org
Ken
K
Uchino
Adrian V
AV
Hernandez
D054058:Acute Coronary Syndrome / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D000328:Adult; D001562:Benzimidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D000069604:Dabigatran; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D013923:Thromboembolism / Q000517:prevention & control*; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D001562:Benzimidazoles; D015091:beta-Alanine; D000069604:Dabigatran