Packer M, Bristow M R, Cohn J N, Colucci W S, Fowler M B, Gilbert E M, Shusterman N H
Division of Circulatory Physiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
N Engl J Med. 1996 May 23;334(21):1349-55. doi: 10.1056/NEJM199605233342101.
Controlled clinical trials have shown that beta-blockers can produce hemodynamic and symptomatic improvement in chronic heart failure, but the effect of these drugs on survival has not been determined.
We enrolled 1094 patients with chronic heart failure in a double-blind, placebo-controlled, stratified program, in which patients were assigned to one of the four treatment protocols on the basis of their exercise capacity. Within each of the four protocols patients with mild, moderate, or severe heart failure with left ventricular ejection fractions < or = 0.35 were randomly assigned to receive either placebo (n = 398) or the beta-blocker carvedilol (n = 696); background therapy with digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor remained constant. Patient were observed for the occurrence death or hospitalization for cardiovascular reasons during the following 6 months, after the beginning (12 months for the group with mild heart failure).
The overall mortality rate was 7.8 percent in the placebo group and 3.2 percent in the carvedilol group; the reduction in risk attributable to carvedilol was 65 percent (95 percent confidence interval, 39 to 80 percent; P < 0.001). This finding led the Data and Safety Monitoring Board to recommend termination of the study before its scheduled completion. In addition, as compared with placebo, carvedilol therapy was accompanied by a 27 percent reduction in the risk of hospitalization for cardiovascular causes (19.6 percent vs. 14.1 percent, P = 0.036), as well as a 38 percent reduction in the combined risk of hospitalization or death (24.6 percent vs, 15.8 percent, P < 0.001). Worsening heart failure as an adverse reaction during treatment was less frequent in the carvedilol than in the placebo group.
Carvedilol reduces the risk or death as well as the risk of hospitalization for cardiovascular causes in patients with heart failure who are receiving treatment with digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor.
对照临床试验表明，β受体阻滞剂可使慢性心力衰竭患者的血流动力学及症状得到改善，但这些药物对生存率的影响尚未确定。
我们将1094例慢性心力衰竭患者纳入一项双盲、安慰剂对照、分层试验，根据运动能力将患者分配至四种治疗方案之一。在这四种方案中，左心室射血分数≤0.35的轻度、中度或重度心力衰竭患者被随机分配接受安慰剂（n = 398）或β受体阻滞剂卡维地洛（n = 696）治疗；地高辛、利尿剂和血管紧张素转换酶抑制剂的背景治疗保持不变。开始治疗后（轻度心力衰竭组为12个月），观察患者在接下来6个月内发生心血管原因死亡或住院的情况。
安慰剂组的总死亡率为7.8%，卡维地洛组为3.2%；卡维地洛所致的风险降低为65%（95%置信区间为39%至80%；P < 0.001）。这一结果促使数据与安全监测委员会建议在预定结束前终止该研究。此外，与安慰剂相比，卡维地洛治疗使心血管原因住院风险降低27%（19.6%对14.1%，P = 0.036），住院或死亡的联合风险降低38%（24.6%对15.8%，P < 0.001）。治疗期间作为不良反应的心力衰竭恶化在卡维地洛组比安慰剂组少见。
对于正在接受地高辛、利尿剂和血管紧张素转换酶抑制剂治疗的心力衰竭患者，卡维地洛可降低死亡风险以及心血管原因住院风险。
