Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) Trial
Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) Trial
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DOI：
10.1001/jama.289.16.2073
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发表时间：
2003-04-23
影响因子：
120.7
通讯作者：
Anders, RJ
中科院分区：
文献类型：
--
作者：
Black, HR;Elliott, WJ;Anders, RJ
背景高血压患者经常给予钙拮抗剂以降低心血管疾病的风险，但与其他药物类别相比的益处是有争议的。目的确定在预防心血管疾病方面，控制起效延长释放（COER）维拉帕米的初始治疗是否等同于医生选择的阿替洛尔或氢氯噻嗪。在15个国家的661个中心进行的随机临床试验。在1996年9月至1998年12月期间，共有16602名被诊断为高血压且有1个或多个额外心血管疾病危险因素的参与者入选，并随访至2000年12月31日。经过平均3年的随访，主办方关闭了研究之前揭盲的results.Intervention最初，8241名参与者接受了180毫克的COER维拉帕米和8361接受了50毫克的阿替洛尔或12.5毫克的氢氯噻嗪。其他药物如果需要，可以按特定顺序添加利尿剂、β受体阻滞剂或血管紧张素转换酶抑制剂。或心血管疾病-结果COER维拉帕米组的收缩压和舒张压分别降低13.6 mm Hg和7.8 mm Hg，COER维拉帕米组的收缩压和舒张压分别降低13.5 mm Hg和7.1 mm Hg对于分配至ateholol或氢氯噻嗪组的受试者。COER维拉帕米组有364例原发性心血管疾病相关事件，阿替洛尔或氢氯噻嗪组有365例（风险比[HR]，1.02; 95%置信区间[CI]，0.88-1.18; P= 0.77）。对于致死性或非致死性卒中，HR为1.15（95% CI，0.90-1.48）;对于致死性或非致死性心肌梗死，HR为0.82（95% CI，0.65-1.03）;对于心血管疾病相关死亡，HR为1.09（95% CI，0.87-1.37）。任何预先规定的心血管疾病相关事件的HR为1.05（95% CI，0.95-1.16），全因死亡率的HR为1.08（95% CI，0.93-1.26）。与阿替洛尔或氢氯噻嗪组（n=79）相比，COER-维拉帕米组（n=118）的受试者非卒中出血更常见（HR，1.54 [95% CI，1.16-2.04]; P=.003）。COER维拉帕米组（99/277）和阿替洛尔或氢氯噻嗪组（88/274）在上午6点至中午之间发生更多的心血管疾病相关事件; FIR，1.15（95%CI，0.86-1.53）。结论CONVINCE试验并未证明COER维拉帕米为基础的降压方案与利尿剂或β受体阻滞剂为基础的降压方案具有等效性。当在其他钙拮抗剂试验的背景下考虑时，这些数据表明钙通道治疗在减少心血管疾病方面的有效性与利尿剂或β受体阻滞剂治疗相似，但并不优于利尿剂或β受体阻滞剂治疗。
Context Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial.Objective To determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease.Design, Setting, and Participants Double-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results.Intervention Initially, 8241 participants received 180 mg of COER Verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, beta-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed.Main Outcome Measures First occurrence of stroke, myocardial infarction, or cardiovascular disease-related death.Results Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the ateholol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.88-1.18; P=.77). For fatal or nonfatal stroke, the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95% Cl, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Non-stroke hemorrhage was more common with participants in the COER-verapamil group (n=118) compared with the atenolol or hydrochlorothiazide group (n=79) (HR, 1.54 [95% CI, 1.16-2.04]; P=.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; FIR, 1.15 (95% CI, 0.86-1.53).Conclusions The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or beta-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or beta-blocker treatment.