Hauf-Zachariou U, Blackwood R A, Gunawardena K A, O'Donnell J G, Garnham S, Pfarr E
Department of Clinical Research, Boehringer Mannheim GmbH, Germany.
Eur J Clin Pharmacol. 1997;52(2):95-100. doi: 10.1007/s002280050256.
In a multicentre, double-blind, parallel group study, the anti-anginal and the anti-ischaemic efficacy of 12 weeks of therapy with the vasodilating beta-adrenoceptor-blocker carvedilol 25 mg b.i.d. was compared with verapamil 120 mg t.i.d.
During a 2-week placebo run-in period, patients were required to have two treadmill exercise tests (modified Bruce Protocol) differing by not more than 15% with regard to total exercise time (TET). Of 313 patients enrolled, 248 were randomized and 212 completed the study according to the protocol.
The primary variable TET was analysed using the Cox Proportional Hazards Model to take into account censored values due to the patient stopping the exercise test for reasons other than angina. Forty-three per cent of patients allocated to carvedilol and 36% to verapamil did not stop with angina at the final visit. There was no difference in the TET between the groups, the risk ratio being 1.14 in favour of carvedilol (90% CI 0.85-1.52). TET increased from 378 s at baseline to 436 s at the final visit in the carvedilol group and from 386 to 438 s in the verapamil group. Results for time to angina and time to 1 mm ST-segment depression were similar. Compared to verapamil, carvedilol significantly reduced HR, systolic BP and rate pressure product at peak exercise. Analysis of 48 h Holter monitor data showed a greater reduction of HR and PVCs with carvedilol. Lown grading improved in both groups. Adverse events were reported by 48% (3.2% serious adverse events) of patients taking carvedilol and 58% (5.7% serious adverse events) taking verapamil.
Carvedilol is at least as effective as verapamil in the management of chronic stable angina and demonstrated a favourable adverse event profile.
在一项多中心、双盲、平行组研究中，比较了血管舒张性β肾上腺素受体阻滞剂卡维地洛25mg每日两次治疗12周的抗心绞痛和抗缺血疗效与维拉帕米120mg每日三次的疗效。
在为期2周的安慰剂导入期内，要求患者进行两次平板运动试验（改良Bruce方案），总运动时间（TET）相差不超过15%。在纳入的313例患者中，248例被随机分组，212例按方案完成了研究。
使用Cox比例风险模型分析主要变量TET，以考虑因患者因非心绞痛原因停止运动试验而产生的删失值。分配到卡维地洛组的患者中有43%以及分配到维拉帕米组的患者中有36%在最后一次访视时并非因心绞痛而停止试验。两组之间的TET无差异，风险比为1.14，有利于卡维地洛（90%可信区间0.85 - 1.52）。卡维地洛组的TET从基线时的378秒增加到最后一次访视时的436秒，维拉帕米组从386秒增加到438秒。心绞痛发作时间和ST段压低1mm的时间结果相似。与维拉帕米相比，卡维地洛在运动高峰时显著降低心率、收缩压和心率血压乘积。对48小时动态心电图监测数据的分析显示，卡维地洛对心率和室性早搏的降低幅度更大。两组的Lown分级均有所改善。服用卡维地洛的患者中有48%（严重不良事件为3.2%）报告了不良事件，服用维拉帕米的患者中有58%（严重不良事件为5.7%）报告了不良事件。
卡维地洛在治疗慢性稳定型心绞痛方面至少与维拉帕米一样有效，并显示出良好的不良事件谱。
