Kotecha Dipak, Manzano Luis, Krum Henry, Rosano Giuseppe, Holmes Jane, Altman Douglas G, Collins Peter D, Packer Milton, Wikstrand John, Coats Andrew J S, Cleland John G F, Kirchhof Paulus, von Lueder Thomas G, Rigby Alan S, Andersson Bert, Lip Gregory Y H, van Veldhuisen Dirk J, Shibata Marcelo C, Wedel Hans, Böhm Michael, Flather Marcus D
University of Birmingham Institute of Cardiovascular Sciences, Birmingham, UK Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, Australia
Internal Medicine Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
BMJ. 2016 Apr 20;353:i1855. doi: 10.1136/bmj.i1855.
To determine the efficacy and tolerability of β blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials.
Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45.
13,833 patients from 11 trials; median age 64; 24% women.
The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model.
Compared with placebo, β blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by β blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give β blockers, 15.6% in those receiving placebo).
Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive β blockers to reduce the risk of death and admission to hospital.Registration PROSPERO CRD42014010012; Clinicaltrials.gov NCT00832442.
通过汇总安慰剂对照随机试验中的个体患者数据，确定β受体阻滞剂对广泛年龄范围的射血分数降低的心力衰竭（HFrEF）男女患者的疗效和耐受性。
对基线时窦性心律、左心室射血分数<0.45、年龄在40 - 85岁的患者的个体患者数据进行前瞻性设计的荟萃分析。
来自11项试验的13833名患者；中位年龄64岁；24%为女性。
主要结局为全因死亡率；主要次要结局为因心力衰竭住院。采用调整后的单阶段Cox比例风险模型进行意向性治疗分析。
与安慰剂相比，β受体阻滞剂在所有年龄段均能有效降低死亡率：年龄分布第一季度（中位年龄50岁）的风险比为0.66（95%置信区间0.53至0.83）；第二季度（中位年龄60岁）为0.71（0.58至0.87）；第三季度（中位年龄68岁）为0.65（0.53至0.78）；第四季度（中位年龄75岁）为0.77（0.64至0.92）。对年龄进行连续建模时无显著交互作用（P = 0.1），在中位随访1.3年期间死亡率的绝对降低为4.3%（需治疗人数23）。β受体阻滞剂显著降低了因心力衰竭住院的发生率，尽管这种效应在老年时减弱（交互作用P = 0.05）。在任何年龄组中均无证据表明治疗效果与性别之间存在交互作用。无论治疗分配、年龄或性别如何，停药情况相似（给予β受体阻滞剂者为14.4%，接受安慰剂者为15.6%）。
无论年龄或性别，窦性心律的HFrEF患者均应接受β受体阻滞剂治疗以降低死亡和住院风险。
PROSPERO CRD42014010012；Clinicaltrials.gov NCT00832442。
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