Ivabradine

Abstract

Ivabradine (Procoralan®) is a pure heart rate-lowering drug that produces selective and specific inhibition of the cardiac pacemaker funny current (I(f)) in the sinus node that regulates heart rate. The drug acts directly on the sinus node and does not affect atrioventricular or intraventricular conduction times, myocardial contractility or ventricular repolarization. Ivabradine is used in the treatment of adults with New York Heart Association class II-IV chronic heart failure with systolic dysfunction, in sinus rhythm, with a heart rate of ≥75 beats per minute (bpm). This article reviews the pharmacology of ivabradine, and data on its clinical profile in adults with chronic heart failure. The large, randomized, double-blind, placebo-controlled, multicenter, SHIFT (Systolic Heart failure treatment with the I(f) inhibitor ivabradine Trial) study was conducted to evaluate the effect of reducing heart rate with ivabradine on outcomes in adults with symptomatic chronic heart failure and left ventricular systolic dysfunction, in sinus rhythm, and with a resting heart rate of ≥70 bpm, receiving stable background therapy. Study participants had reduced left ventricular ejection fraction of ≤35%. Results from the SHIFT study showed that compared with placebo (n = 3264), a clinically and statistically significant reduction of 18% in the relative risk of the primary composite endpoint (i.e. the composite of cardiovascular death or hospital admission for worsening heart failure) occurred in the ivabradine treatment group (n = 3241) within 3 months of the start of treatment. Study treatment was discontinued by significantly more ivabradine than placebo recipients in the SHIFT study; however, the incidence of serious adverse events was significantly higher in the placebo treatment group. Cardiovascular adverse events, including bradycardia, were the most common adverse events reported with ivabradine.