According to a meta-analysis published early online in the Archives of Internal Medicine, dabigatran is associated with an increased risk of myocardial infarction (MI) or acute coronary syndromes (ACS) in a broad spectrum of patients when tested against different controls.
The meta-analysis of randomised controlled trials incorporated data from 7 trials (involving a total of 30,514 patients) which met inclusion criteria, reporting MI or ACS events as secondary outcomes. The primary outcomes were acute coronary events: MI or ACS (confirmed unstable angina, MI, and cardiac death) if the study did not report MI as an adverse event. Overall mortality was the secondary outcome. Two studies involved the evaluation of dabigatran for stroke prevention in patients with atrial fibrillation (AF), 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. The following results were reported:
• Dabigatran was 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, 1.33; 95% CI, 1.03-1.71; P = 0.03).
• The risk of MI or ACS was similar when using revised RE-LY trial results (OR, 1.27; 1.00-1.61; P = 0.05) or after exclusion of short-term trials (OR, 1.33; 1.03-1.72; P = 0.03).
• Six studies reported on overall mortality. Dabigatran was associated with lower mortality than the control group (dabigatran, 945 of 19,555 [4.83%] vs control, 524 of 10 444 [5.02%]; OR, 0.89; 95% CI, 0.80-0.99; P=0.04).
The authors conclude that this meta-analysis indicates that the risk of MI or ACS is increased with dabigatran compared with various control treatments, which included adjusted-dose warfarin, enoxaparin, or placebo. However, although the relative risk increase was 33%, the absolute risk increase was very small, at 0.27%. The overall benefit and risk balance of dabigatran use appears to be favourable in patients with AF because of reduction in ischaemic stroke. However, the cardiac risk of dabigatran should be investigated further, especially if it is used in populations at high risk of MI or ACS.
A related editorial discusses the study.