Ivabradine -- the First Selective Sinus Node I(f) Channel Inhibitor in the Treatment of Stable Angina

Heart rate, a major determinant of angina in coronary disease, is also an important predictor of cardiovascular mortality. Lowering heart rate is therefore one of the most important therapeutic approaches in the treatment of stable angina pectoris. To date, beta-blockers and some calcium-channel antagonists reduce heart rate, but their use may be limited by adverse reactions or contraindications. Heart rate is determined by spontaneous electrical pacemaker activity in the sinoatrial node controlled by the I(f) current. Ivabradine is the first specific heart rate-lowering agent that has completed clinical development for stable angina pectoris. It is selective for the I(f) current, lowering heart rate at concentrations that do not affect other cardiac ionic currents. Specific heart-rate lowering with ivabradine reduces myocardial oxygen demand, simultaneously improving oxygen supply. Ivabradine has no negative inotropic or lusitropic effects, preserving ventricular contractility, and does not change any major electrophysiological parameters unrelated to heart rate. Randomised clinical studies in patients with stable angina show that ivabradine effectively reduces heart rate, improves exercise capacity and reduces the number of angina attacks. It has superior anti-anginal and anti-ischaemic activity to placebo and is non-inferior to atenolol and amlodipine. Ivabradine therefore offers a valuable approach to lowering heart rate exclusively and provides an attractive alternative to conventional treatment for a wide range of patients with confirmed stable angina.