Lechat P, Packer M, Chalon S, Cucherat M, Arab T, Boissel J P
Service de Pharmacologie, Hôpital Pitié-Salpêtrière, Paris, France.
Circulation. 1998 Sep 22;98(12):1184-91. doi: 10.1161/01.cir.98.12.1184.
beta-Blockers have improved symptoms and reduced the risk of cardiovascular events in studies of patients with heart failure, but it is unclear which end points are most sensitive to the therapeutic effects of these drugs.
We combined the results of all 18 published double-blind, placebo-controlled, parallel-group trials of beta-blockers in heart failure. From this combined database of 3023 patients, we evaluated the strength of evidence supporting an effect of treatment on left ventricular ejection fraction, NYHA functional class, hospitalizations for heart failure, and death. beta-Blockers exerted their most persuasive effects on ejection fraction and on the combined risk of death and hospitalization for heart failure. beta-Blockade increased the ejection fraction by 29% (P<10(-9)) and reduced the combined risk of death or hospitalization for heart failure by 37% (P<0.001). Both effects remained significant even if >90% of the trials were eliminated from the analysis or if a large number of trials with a neutral result were added to the analysis. In contrast, the effect of beta-blockade on NYHA functional class was of borderline significance (P=0.04) and disappeared with the addition or removal of only 1 moderate-size study. Although beta -blockade reduced all-cause mortality by 32% (P=0.003), this effect was only moderately robust and varied according to the type of ss-blocker tested, ie, the reduction of mortality risk was greater for nonselective beta-blockers than for beta1-selective agents (49% versus 18%, P=0.049). However, selective and nonselective beta-blockers did not differ in their effects on other measures of clinical efficacy.
These analyses indicate that there is persuasive evidence supporting a favorable effect of beta-blockade on ejection fraction and the combined risk of death and hospitalization for heart failure. In contrast, the effect of these drugs on other end points requires additional study.
在心力衰竭患者的研究中，β受体阻滞剂改善了症状并降低了心血管事件的风险，但尚不清楚哪些终点对这些药物的治疗效果最为敏感。
我们汇总了已发表的18项关于β受体阻滞剂治疗心力衰竭的双盲、安慰剂对照、平行组试验的结果。从这个包含3023例患者的综合数据库中，我们评估了支持治疗对左心室射血分数、纽约心脏协会（NYHA）心功能分级、因心力衰竭住院及死亡影响的证据强度。β受体阻滞剂对射血分数以及心力衰竭死亡和住院的综合风险产生了最具说服力的影响。β受体阻滞使射血分数提高了29%（P<10⁻⁹），并使心力衰竭死亡或住院的综合风险降低了37%（P<0.001）。即使从分析中剔除>90%的试验，或者在分析中加入大量结果为中性的试验，这两种效应仍然显著。相比之下，β受体阻滞对NYHA心功能分级的影响处于临界显著水平（P=0.04），仅增减一项中等规模研究就会使其消失。虽然β受体阻滞使全因死亡率降低了32%（P=0.003），但这种效应仅具有中等强度，且因所测试的β受体阻滞剂类型而异，即非选择性β受体阻滞剂降低死亡风险的幅度大于β1选择性药物（49%对18%，P=0.049）。然而，选择性和非选择性β受体阻滞剂在其他临床疗效指标上的作用并无差异。
这些分析表明，有充分证据支持β受体阻滞对射血分数以及心力衰竭死亡和住院的综合风险具有有益影响。相比之下，这些药物对其他终点的影响需要进一步研究。
