Effects of initiating carvedilol in patients with severe chronic heart failure - Results from the COPERNICUS study
Effects of initiating carvedilol in patients with severe chronic heart failure - Results from the COPERNICUS study
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DOI：
10.1001/jama.289.6.712
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发表时间：
2003-02-12
影响因子：
120.7
通讯作者：
Packer, M
中科院分区：
文献类型：
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作者：
Krum, H;Roecker, EB;Packer, M
背景β受体阻滞剂仍然未得到充分利用，尽管它们已被证实可用于改善心力衰竭的结局。研究设计：随机、双盲、安慰剂对照试验，从1997年10月28日至2000年3月20日进行。在21个国家的334个医院中心，对2289名在静息或轻微运动时有心力衰竭症状的患者进行了研究，这些患者临床上是正常血容量的，左心室射血分数低于25%。起始剂量为3.125 mg，每日两次，上调至目标剂量25 mg，每日两次（n=1156），或安慰剂（n=1133），除常规治疗心力衰竭的药物外。主要结果测量死亡，住院，结果卡维地洛组心血管风险没有增加，但死亡人数减少（19 vs 25;风险比[HR]，0.75; 95%置信区间[CI]，0.41-1.35）;死亡或住院（134 vs 153; HR，0.85; 95% CI，0.67-1.07）;或死亡、住院或永久退出治疗（162 vs 188; HR，0.83; 95% CI，0.68-1.03）。这些影响在方向和程度上与整个研究期间观察到的相似，特别是在624例近期或复发性失代偿或左心室射血分数非常低的患者中。早在治疗开始后14至21天，支持卡维地洛的差异就变得明显。心力衰竭恶化是唯一的严重不良事件的频率大于2%，并报告了类似的频率在安慰剂和卡维地洛组（6.4%比5.1%）。结论这些数据表明，在临床上血容量正常的患者，在开始治疗卡维地洛的获益与风险的关系是类似的长期治疗过程中看到的药物。我们的研究结果应该提供必要的保证，以鼓励长期临床试验结果所保证的高水平使用。
Context beta-Blockers remain underused despite their established utility for improving outcome in heart failure. Concerns that initiation of treatment produces few immediate benefits and may have important risks may be deterring widespread use.Objective To evaluate the early effects of the beta-blocker carvedilol in patients with severe heart failure.Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial conducted from October 28, 1997, to March 20, 2000, at 334 hospital centers in 21 countries among 2289 patients with symptoms of heart failure at rest or with minimal exertion who were clinically euvolemic and had a left ventricular ejection fraction of less than 25%.Intervention Patients were randomly assigned to receive carvedilol, with start dosage of at 3.125 mg twice daily with uptitration to a target dosage of 25 mg twice daily (n=1156), or placebo (n=1133), in addition to their usual medications for heart failure.Main Outcome Measures Death, hospitalization, or permanent withdrawal from study drug, as well as adverse events during the first 8 weeks of treatment.Results The carvedilol group experienced no increase in cardiovascular risk but instead had fewer patients who died (19 vs 25; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.41-1.35); who died or were hospitalized (134 vs 153; HR, 0.85; 95% CI, 0.67-1.07); or who died, were hospitalized, or were permanently withdrawn from treatment (162 vs 188; HR, 0.83; 95% CI, 0.68-1.03). These effects were similar in direction and magnitude to those observed during the entire study, and were apparent particularly in the 624 patients with recent or recurrent decompensation or a very depressed left ventricular ejection fraction. Differences in favor of carvedilol became apparent as early as 14 to 21 days following initiation of treatment. Worsening heart failure was the only serious adverse event with a frequency greater than 2% and was reported with similar frequency in the placebo and carvedilol groups (6.4% vs 5.1%).Conclusions These data suggest that, in clinically euvolemic patients, the relation of benefit to risk during initiation of treatment with carvedilol is similar to that seen during long-term therapy with the drug. Our findings should provide the reassurance needed to encourage the high levels of use that are warranted by the results of long-term clinical trials.