723-5 Evaluation of the Antianginal and Anti-ischemic Effects of the Sinus Node Inhibitor Zatebradine Used in Combination with Extended-Release Nifedipine In Patients with Angina Pectoris

Abstract

Zatebradine (Z) is a directsinus node inhibitor which is orally active and, unlike p-adrenergic blockers, has no effect on blood pressure, vascular resistances, and ventricular contractility. We evaluated the anginal and anti-ischemic effects of Z 15 mg administered twice daily) and placebo in 124 patients (pts) already receiving 30–90 mg of extended-release nifedipine once daily, whose treadmill exercise tolerance was still limited. After 2–3 wks of single-blind placebo therapy with reproducible exercise-induced angina on the treadmill, pts were randomized to receive in double-blind fashion twice daily Z (n = 64) or twice daily placebo (n = 60) in addition to nifedipine. Subjects were followed with serial exercise tests 13 hrs post dose) for 4 wks and angina diaries were maintained. At 4 wks, Z was shown to reduce resting heart rate (HR) in contrast to placebo (12.9 ± 1,23 vs 2.3 ± 1.6 bpm, p < 0.0001), and at the end of comparable stages of exercise (Bruce). Z reduced HR in contrast to placebo (16.7 ± 1.2 vs 3.4 ± 1.2 bpm, p < 0.001). Despite these significant effects on HR with Z at rest and exercise, there were no additional antianginal benefits of Z from placebo baseline in measurements of total exercise duration, time to 1 mm ST segment depression, or time to onset of angina. Z appears to provide no additional antianginal benefit to pts already receiving nifedipine, and raises questions regarding the benefit of HR reduction alone as an antianginal approach in pts.