Sinus Node If Channel Inhibition – A New Therapeutic Approach to Heart Rate Lowering

Abstract

Heart rate lowering has an important role in the treatment of coronary artery disease. Lower heart rates extend diastolic filling, facilitating improved myocardial perfusion and reduced myocardial oxygen demand. This has traditionally been achieved with beta-blockers or calcium-channel blockers. Unfortunately both these classes of drugs have sideeffects in a significant minority of patients. The recent development of ivabradine, which acts specifically on the sinoatrial node, offers promise in achieving heart rate reduction without major side effects. Ivabradine selectively and specifically inhibits the If channel which is integral to the generation of the pacemaker current in the sinoatrial node. Initial studies utilising ivabradine show improvements in exercise tolerance and time to developing ischaemia during exercise in patients with chronic stable angina. Ivabradine has no negative inotropic effects and does not appear to have any major side-effects. It has been shown to have similar antianginal and anti-ischaemic effects to atenolol and amlodipine. Animal studies have suggested that ivabradine may have beneficial effects in chronic heart failure leading to improvements in left ventricular function. In humans with stable coronary artery disease, left ventricular dysfunction and heart rates of 70bpm or more, ivabradine appears to reduce rates of revascularisation and hospitalisation for myocardial infarction.