Author + information
- Received December 6, 1994
- Revision received March 22, 1995
- Accepted March 31, 1995
- Published online August 1, 1995.
- William H. Frishman, MD, FACC1,a,
- Carl J. Pepine, MD, FACCb,
- Robert J. Weiss, MD, FACCc and
- Wolfgang M. Baiker, MDd
- ↵1Address for correspondence: William H. Frishman, MD, Jack D. Weiler Hospital of the Albert Einstein College of Medicine, 1825 Eastchester Road, Bronx, New York 10461.
Objectives. We examined the antianginal and anti-ischemic effects of oral zatebradine, a direct sinus node inhibitor that has no blood pressure-lowering or negative inotropic effects in patients with chronic stable angina pectoris taking extended-release nifedipine.
Background. Heart rate reduction is considered an important pharmacologic mechanism for providing anginal pain relief and anti-ischemic action in patients with chronic stable angina, suggesting a benefit for sinus node-inhibiting drugs.
Methods. In a single-blind placebo run-in, randomized double-blind, placebo-controlled, multicenter study, patients already receiving extended-release nifedipine (30 to 90 mg once a day) were randomized to receive zatebradine (5 mg twice a day [n = 64]) or placebo (n = 60). All subjects had reproducible treadmill exercise-induced angina at baseline, and after randomization they performed a serial exercise test 3 h after each dose for 4 weeks.
Results. Zatebradine reduced rest heart rate both at 4 weeks ([mean ± SEM] 12.9 ± 1.23 vs. 2.3 ± 1.6 [placebo] beats/min, p < 0.0001) and at the end of comparable stages of Bruce exercise (16.7 ± 1.2 vs. 3.4 ± 1.2 [placebo] beats/min, p < 0.0001). Despite the significant effects on heart rate at rest and exercise, there were no additional benefits of zatebradine from placebo baseline in measurements of total exercise duration, time to 1-mm ST segment depression or time to onset of angina. Subjects taking zatebradine also had more visual disturbances as adverse reactions.
Conclusions. Zatebradine seems to provide no additional anti-anginal benefit to patients already receiving nifedipine, and it raises questions regarding the benefit of heart rate reduction alone as an antianginal approach to patients with chronic stable angina.
☆ This study was supported by a grant from Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut.
- Received December 6, 1994.
- Revision received March 22, 1995.
- Accepted March 31, 1995.