Clinical Medicine Insights: Therapeutics

The first selective If current inhibitor, ivabradine, lowers heart rate (HR) at rest and during exercise with no vasomotor, negative inotropic, or negative lusitropic effects. Given that elevated resting HR is a key factor in the onset of myocardial ischemia and a strong independent predictor of cardiovascular outcomes, ivabradine provides new therapeutic prospects in coronary artery disease (CAD). Its selective HR-lowering action has proven anti-ischemic and anti-anginal efficacy, and ivabradine is currently indicated for the symptomatic treatment of stable angina pectoris. Ivabradine can also be safely combined with other anti-anginal agents, and addition of ivabradine to beta-blocker therapy further improves anti-ischemic efficacy and exercise capacity of patients with stable angina. The recent BEAUTIFUL trial demonstrated that although the primary endpoint was not met in the overall population, addition of ivabradine on top of standard preventive treatments significantly reduced the risk of coronary events in stable CAD patients with left ventricular systolic dysfunction among the subgroup of patients with a resting HR ≥ 70 bpm. This is in accordance with pre-clinical data showing that long-term HR reduction improves endothelial function and reduces the progression of atherosclerosis. A significant proportion of patients with stable angina have elevated resting HR and ivabradine should therefore be considered as an important therapy in these cases. In combination with other standard treatments, ivabradine can improve angina and could potentially improve coronary outcomes. Ongoing and future clinical studies will evaluate the presence and magnitude of the cardio-protective benefits of HR lowering with ivabradine in patients with cardiovascular diseases.