Aims Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF ≥ 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Conclusion Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.

中文翻译：

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β-受体阻滞剂治疗射血分数降低、中等和保留的心力衰竭：双盲随机试验的个体患者水平分析


目标 最近的指南建议，心力衰竭且左心室射血分数 (LVEF) 为 40-49% 的患者应采用类似于 LVEF ≥ 50% 的治疗方法。我们根据 LVEF 在双盲、随机、安慰剂对照试验中研究了 β 受体阻滞剂的效果。方法和结果 对 11 项试验的个体患者数据进行荟萃分析，按基线 LVEF 和心律分层（Clinicaltrials.gov：NCT0083244；PROSPERO：CRD42014010012）。主要结局是中位随访 1.3 年的全因死亡率和心血管死亡，并进行意向治疗分析。对于 14 262 名窦性心律患者，中位 LVEF 为 27%（四分位数范围 21-33%），其中 575 名患者 LVEF 为 40-49%，244 名 ≥ 50%。与安慰剂相比，β-受体阻滞剂降低了窦性心律下的全因死亡率和心血管死亡率，这种效果在整个 LVEF 各层中是一致的，除了 LVEF ≥ 50% 的小亚组。对于 LVEF 40-49% 的患者，随机接受 β 受体阻滞剂治疗的患者中有 21/292 [7.2%] 发生死亡，而安慰剂组的死亡人数为 35/283 [12.4%]；调整后的风险比 (HR) 0.59 [95% 置信区间 (CI) 0.34-1.03]。 β-受体阻滞剂组中 13/292 [4.5%] 发生心血管死亡，安慰剂组中 26/283 [9.2%] 发生心血管死亡；调整后 HR 0.48 (95% CI 0.24-0.97)。随机化后中位 1.0 年 (n = 4601)，除 LVEF ≥ 50% 外，所有窦性心律组中使用 β 受体阻滞剂后 LVEF 均有所增加。对于基线时患有房颤的患者 (n = 3050)，当基线时 LVEF < 50% 时，β 受体阻滞剂会增加 LVEF，但不会改善预后。结论 β 受体阻滞剂可改善 LVEF 降低的窦性心律心力衰竭患者的 LVEF 和预后。 LVEF < 40% 的数据最为稳健，但在 LVEF 40-49% 的患者亚组中也观察到了类似的益处。