Physiological effects of ivabradine in heart failure and beyond

Ivabradine is a pharmacologic agent that inhibits the funny current responsible for determining heart rate in the sinoatrial node. Ivabradine's clinical potential has been investigated in the context of heart failure since it is associated with reduced myocardial oxygen demand, enhanced diastolic filling, stroke volume, and coronary perfusion time; however, it is yet to demonstrate definitive mortality benefit. Alternative effects of ivabradine include modulation of the renin-angiotensin-aldosterone system, sympathetic activation, and endothelial function. Here, we review key clinical trials informing the clinical use of ivabradine and explore opportunities for leveraging its potential pleiotropic effects in other diseases, including treatment of hyperadrenergic states and mitigating complications of COVID-19 infection.