Frishman W H, Pepine C J, Weiss R J, Baiker W M
Department of Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA.
J Am Coll Cardiol. 1995 Aug;26(2):305-12. doi: 10.1016/0735-1097(95)80000-7.
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.
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.
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.
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.
Zatebradine seems to provide no additional antianginal 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.
我们研究了口服扎替雷定（一种直接的窦房结抑制剂）对慢性稳定型心绞痛患者的抗心绞痛和抗缺血作用，这些患者正在服用缓释硝苯地平，且扎替雷定无降压或负性肌力作用。
心率降低被认为是为慢性稳定型心绞痛患者缓解心绞痛疼痛和发挥抗缺血作用的重要药理机制，这表明窦房结抑制药物可能有益。
在一项单盲安慰剂导入、随机双盲、安慰剂对照、多中心研究中，已在服用缓释硝苯地平（每日一次，30至90毫克）的患者被随机分配接受扎替雷定（每日两次，5毫克[n = 64]）或安慰剂（n = 60）。所有受试者在基线时均有可重复性的平板运动诱发心绞痛，随机分组后，他们在每次给药后3小时进行连续运动试验，共进行4周。
扎替雷定在4周时（[均值±标准误]12.9±1.23对2.3±1.6[安慰剂]次/分钟，p < 0.0001）以及布鲁斯运动相当阶段结束时（16.7±1.2对3.4±1.2[安慰剂]次/分钟，p < 0.0001）均降低了静息心率。尽管对静息和运动时的心率有显著影响，但在总运动持续时间、1毫米ST段压低时间或心绞痛发作时间的测量中，与安慰剂基线相比，扎替雷定并无额外益处。服用扎替雷定的受试者还出现了更多视觉障碍等不良反应。
扎替雷定似乎对已服用硝苯地平的患者没有额外的抗心绞痛益处，这也引发了对于仅通过降低心率作为慢性稳定型心绞痛患者抗心绞痛方法的益处的质疑。
