Frishman W H, Glasser S, Stone P, Deedwania P C, Johnson M, Fakouhi T D
Department of Medicine, New York Medical College, Valhalla 10595, USA.
Am J Cardiol. 1999 Feb 15;83(4):507-14. doi: 10.1016/s0002-9149(98)00904-7.
This multicenter, randomized, double-blind, parallel group, placebo lead-in, placebo-controlled study compared the antianginal and anti-ischemic effects of once-daily bedtime dosing of controlled-onset extended-release (COER-24) verapamil to a once-daily morning dosing of amlodipine +/- atenolol in patients with chronic stable angina. A total of 551 patients with exercise-induced myocardial ischemia and evidence of coronary artery disease were randomized to a 4-week, forced-dose titration treatment period with (1) COER-24 verapamil 240 mg titrated to 480 mg at bedtime (n = 173), (2) amlodipine 5 mg titrated to 10 mg/day (n = 149), (3) amlodipine 5 mg (titrated to 10 mg) plus atenolol 50 mg/day in the A.M. (n = 154), or (4) placebo (n = 75). Treadmill exercise tolerance testing (standard Bruce protocol), and 48-hour ambulatory electrocardiographic (Holter) monitoring were performed at the end of placebo lead-in and double-blind treatment. Each active treatment significantly improved symptom-limited exercise duration and time to moderate angina (p < or = 0.01 vs placebo). For patients with baseline ischemia, amlodipine resulted in a statistically significant increase in total duration of ischemic episodes compared with placebo, whereas COER-24 verapamil and amlodipine plus atenolol resulted in statistically significant decreases compared with placebo and amlodipine. Heart rate at onset of ischemic episodes and ST product were also significantly increased with amlodipine (p < 0.05) compared with either COER-24 or amlodipine plus atenolol. COER-24 and amlodipine alone or in combination with atenolol improved exercise capacity in patients with angina pectoris. COER-24 verapamil monotherapy or amlodipine plus atenolol combination therapy were more effective than amlodipine monotherapy in decreasing ambulatory myocardial ischemia, especially during the hours of 6 A.M. to 12 noon.
这项多中心、随机、双盲、平行组、安慰剂导入、安慰剂对照研究比较了慢性稳定型心绞痛患者每日一次睡前服用控释长效（COER - 24）维拉帕米与每日一次早晨服用氨氯地平+/-阿替洛尔的抗心绞痛和抗缺血作用。共有551例运动诱发心肌缺血且有冠状动脉疾病证据的患者被随机分配到为期4周的强制剂量滴定治疗期，治疗方案为：（1）睡前服用COER - 24维拉帕米240 mg，滴定至480 mg（n = 173）；（2）氨氯地平5 mg，滴定至10 mg/天（n = 149）；（3）上午服用氨氯地平5 mg（滴定至10 mg）加阿替洛尔50 mg/天（n = 154）；或（4）安慰剂（n = 75）。在安慰剂导入期和双盲治疗结束时进行了平板运动耐量测试（标准Bruce方案）和48小时动态心电图（Holter）监测。每种活性治疗均显著改善了症状限制运动持续时间和中度心绞痛发作时间（与安慰剂相比，p≤0.01）。对于基线有缺血的患者，与安慰剂相比，氨氯地平使缺血发作总持续时间有统计学意义的增加，而COER - 24维拉帕米和氨氯地平加阿替洛尔与安慰剂和氨氯地平相比，使缺血发作总持续时间有统计学意义的减少。与COER - 24或氨氯地平加阿替洛尔相比，氨氯地平使缺血发作开始时的心率和ST段乘积也显著增加（p < 0.05）。COER - 24和单独使用氨氯地平或与阿替洛尔联合使用均可改善心绞痛患者的运动能力。COER - 24维拉帕米单药治疗或氨氯地平加阿替洛尔联合治疗在减少动态心肌缺血方面比氨氯地平单药治疗更有效，尤其是在上午6点至中午12点期间。
