Specific and selective If inhibition: expected clinical benefits from pure heart rate reduction in coronary patients

Heart rate is increasingly being considered as a prognostic factor in cardiovascular disease, and the need to measure and control heart rate in all coronary patients is clear. When comparisons of heart rate and life expectancy are adjusted for body weight in mammals, it appears that life span is pre-determined by the basic energetics of living cells. This inverse relationship between heart rate and life expectancy reflects an epiphenomenon in which heart rate is a marker for, or a determinant of, metabolic rate and energetic needs. The heart rate is controlled by the If current, which plays a central role as a pacemaker in the sinoatrial node. Ivabradine, the first representative of a new class of exclusive heart rate-reducing agents, selectively inhibits the If current in the sinoatrial node. The direct electrophysiological consequence of this inhibition is a reduction in the slope of the diastolic depolarization curve and a decrease in heart rate. Pharmacological inhibition of the If current with ivabradine has been shown to preserve coronary vasodilatation upon exercise, i.e. myocardial perfusion, with no negative inotropic effects and maintenance of cardiac contractility. Ivabradine also protects the myocardium during ischaemia, improves left ventricular function in congestive heart failure, and reduces remodelling subsequent to myocardial infarction. Pure heart rate reduction by specific and selective If inhibition decreases oxygen demand and improves myocardial energetics, and so we can expect distinct clinical benefits from long-term heart rate reduction in patients with chronic ischaemic disease.