CYP3A4 and atrial fibrillation: The increased frequency of nonfatal MI, which is the main “driver” of the unfavorable effect found in ischemic subgroup, can be partially explained by the higher frequency of atrial fibrillation (+1.5%, p < 0.001) in the ivabradine group [20], due to a bradycardia-dependent mechanism (in particular for patients treated with verapamil/diltiazem, or CYP3A4 inhibitors).