Do non-vitamin K antagonist oral anticoagulants increase the risk of myocardial infarction?

Abstract

Non-vitamin K antagonist oral anticoagulants (NOACs), compared with warfarin, have a favorable risk-benefit profile.  However, in the RE-LY study in patients with atrial fibrillation (AF), the number of patients with MI was higher in the dabigatran group as compared to the warfarin group. Many meta-analyses showed that dabigatran treatment led to an increased risk of myocardial infarction (MI).  Large real-world data (RWD) did not confirm an increase in the risk of MI during dabigatran treatment. In our meta-analysis we excluded RWD, and each of the four drugs was evaluated in two key-phase III randomized controlled trials: in patients with AF and patients with AF and chronic coronary syndrome or acute coronary syndrome treated with percutaneous coronary interventions. In each study, warfarin was the comparator for NOACs. In this homogeneous group of patients, dabigatran, in direct comparison with warfarin, significantly increased the risk of MI by about 30%. Moreover, the risk of MI was also significantly higher than the opposite effect of activated factor (F)  X inhibitors (FXa inhibitors) vs. warfarin. In our network meta-analysis, considering individual NOACs in recommended doses, we found an increased risk of MI compared to warfarin only in patients treated with dabigatran 150 mg twice a day and, in particular, 110 mg twice a day. In this review we present evidence supporting our opinion that in patients with AF and coronary stenting, the choice of NOACs (direct FXa vs. thrombin inhibitors) is equally as important as choosing the optimal antiplatelet therapy (single or dual antiplatelet therapy).