Therapeutic effects of I(f) blockade: evidence and perspective.

Heart rate slowing has been accepted for decades as a primary therapeutic approach to prevention (and even to treatment) of angina pectoris. Pure heart rate slowing has not been achieved with previously available rate-slowing pharmacological agents (beta adrenergic blockers, certain calcium channel blockers), all of which have other pharmacological effects that may be beneficial but also may underlie adverse drug effects. Modulation of heart rate is a function of variation in the I(f) current, a sodium-potassium mediated membrane phenomenon that is active physiologically only in the heart's sinoatrial node. Though the current first was described more than 25 years ago, a practical pharmacological method for its inhibition only recently has been developed, tested and approved for use in Europe. The effective drug, ivabradine, has demonstrated anti-anginal, anti-ischemic efficacy and now is being tested for its effect on survival in patients with coronary artery disease and impaired left ventricular function, as well as for heart failure. The data supporting the use of the drug for angina prevention, and the potential for additional applications, are reviewed in this article.