Clinical Pharmacology of If Current Inhibition

Elevated resting heart rate is linked to an increase in both cardiovascular and all-cause mortality, and agents that reduce heart rate have obvious applications in improving the prognosis of coronary artery disease and heart failure. In this short review, we examine the pathophysiological grounds for the original clinical benefits of pure heart rate lowering through the development of a new class of heart-rate-reducing agents. Ivabradine, a novel selective and specific inhibitor of the If pacemaker current in the sinoatrial node cells, is the prototype of this pharmacological class. It has shown anti-ischemic and antianginal efficacy superior to placebo and comparable to β-blockers and calcium channel blockers. In early clinical pharmacological studies, ivabradine was shown to reduce heart rate in a dose-dependent manner without modifying other cardiac parameters such as conduction, contractility, and ventricular repolarization. Ivabradine improves myocardial oxygen delivery and decreases oxygen consumption. Together, these properties make ivabradine a valuable alternative to existing drug therapies for stable angina and other myocardial conditions.