New analyses differ on whether dabigatran raises MI risk

Two analyses published in the past week compared rates of myocardial infarction (MI) in patients taking dabigatran or warfarin and came to differing results.

Initial reports from the RE-LY trial had indicated that in patients with atrial fibrillation, dabigatran could be associated with an elevated rate of MI, although a post-publication reanalysis authorized by the FDA concluded that the difference was not significant. In a new analysis published online by Circulation on Jan. 3, researchers used data from RE-LY to specifically compare rates of MI, unstable angina, cardiac arrest and cardiac death between patients taking dabigatran and those on warfarin. They found that MI occurred in 98 patients on 110 mg of dabigatran, 97 patients on 150 mg of dabigatran, and 75 patients on warfarin. This worked out to annual event rates of 0.82%, 0.81% and 0.64%, a nonsignificant difference (P ≥0.09 for comparison between dabigatran and warfarin).

The analysis also compared the drugs on the composite of adverse events (MI, unstable angina, cardiac arrest, cardiac death), and found annual rates of 3.16% with 110 mg of dabigatran, 3.33% for 150 mg of dabigatran and 3.41% for warfarin, also a nonsignificant difference. When the outcome was expanded to include strokes, systemic embolism, pulmonary embolism, major bleeding and all-cause death (which were the pre-specified events included in the RE-LY trial), annual rates were 7.34% for 110 mg of dabigatran, 7.11% for 150 mg of dabigatran and 7.91% for warfarin. The researchers also divided patients by presence or absence of history of coronary artery disease or MI, and they found no difference in the relative effects of the drugs.

Based on the results, the authors concluded that dabigatran was associated with a nonsignificant increase in MI compared to warfarin, but no increase in other myocardial ischemic events. However, they cautioned that the RE-LY trial was not powered to detect a difference in rates of MI between the various treatments, and that the outcomes included in this analysis were not prespecified. Still, given that dabigatran was associated with lower rates of the combined outcomes measured by the RE-LY trial, any possible increase in MI is likely to be outweighed by the other benefits of the drug, the authors concluded.

However, a meta-analysis published online by Archives of Internal Medicine on Jan. 9 concluded that dabigatran was associated with a significantly higher risk of MI and acute coronary syndrome (ACS). This analysis combined data from the RE-LY trial with six other trials comparing dabigatran with warfarin, enoxaparin, or placebo for stroke prophylaxis, ACS, acute venous thromboembolism and short-term prophylaxis of deep venous thrombosis. Overall, patients on dabigatran had significantly more cases of MI or ACS than those taking any of the other drugs (dabigatran, 237 events in 20,000 patients [1.19%] vs. control, 83 events in 10,514 patients [0.79%]; odds ratio, 1.33; P=0.03). The authors noted that the mechanism behind this association is unknown. They speculated, “Dabigatran might not directly increase the risk of MI, but it may lack the beneficial effects that warfarin and aspirin have in MI prevention.” They agreed with the authors of the first analysis that for patients with atrial fibrillation, the stroke prevention effects of dabigatran make it beneficial overall. However, they called for further investigation of the drug's possible cardiac risks.