Long-Term Safety and Efficacy of Ivabradine in Patients with Chronic Stable Angina

OBJECTIVE: To assess the long-term safety and antianginal efficacy of two doses of ivabradine, a novel selective and specific inhibitor of the sinus node I(f) current. METHODS: In a randomized double-blind, parallel-group study 386 patients with chronic stable angina were randomized to either ivabradine 5 mg b.i.d. (n = 198, group 1) or ivabradine 7.5 mg b.i.d. (n = 188, group 2) for 12 months. Concomitant medication included antithrombotic agents, lipid-lowering agents, long-acting nitrates and dihydropyridine calcium antagonists. Safety was assessed on the basis of reported adverse events at 1, 3, 6, 9 and 12 months. Antianginal efficacy was based on the reduction in the weekly number of angina attacks and in the consumption of short-acting nitrates from month 0 (baseline) to month 12. RESULTS: Ivabradine was well tolerated. Phosphene-like mild transient visual symptoms were the most frequently reported adverse events but led to treatment withdrawal in only 4 patients. Resting heart rate was reduced by 9 bpm in group 1 and 12 bpm in group 2. Sinus bradycardia caused treatment withdrawal in only three cases. The QTc (Bazett) interval did not increase. At month 12 relative to month 0 there was a significant reduction in the number of angina attacks per week. CONCLUSION: Ivabradine at the recommended doses of 5 and 7.5 mg b.i.d. was well tolerated and demonstrated antianginal efficacy in patients with documented coronary artery disease treated with concomitant antianginal medications.