Effect of ivabradine on cardiac arrhythmias: Antiarrhythmic or proarrhythmic?

Cardiac arrhythmias are a major source of mortality and morbidity. Unfortunately, their treatment remains suboptimal. Major classes of antiarrhythmic drugs pose a significant risk of proarrhythmia, and their side effects often outweigh their benefits. Therefore, implantable devices remain the only truly effective antiarrhythmic therapy, and new strategies of antiarrhythmic treatment are required. Ivabradine is a selective heart rate-reducing agent, an inhibitor of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, currently approved for treatment of coronary artery disease and chronic heart failure. In this review, we focus on the clinical and basic science evidence for the antiarrhythmic and proarrhythmic effects of ivabradine. We attempt to dissect the mechanisms behind the effects of ivabradine and indicate the focus of future studies.