Institute of Clinical Sciences, University of Oslo, Sognsvannsveien 9, Oslo, Norway.
Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Sogn Arena, Nydalen, Oslo, Norway.
Eur Heart J Cardiovasc Pharmacother. 2019 Jan 1;5(1):12-20. doi: 10.1093/ehjcvp/pvy034.
Guidelines concerning β-blocker treatment following acute myocardial infarction (AMI) are based on studies undertaken before the implementation of reperfusion and secondary prevention therapies. We aimed to estimate the effect of oral β-blockers on mortality in contemporary post-AMI patients with low prevalence of heart failure and/or reduced left ventricular ejection fraction.
A random effects model was used to synthetize results of 16 observational studies published between 1 January 2000 and 30 October 2017. Publication bias was evaluated, and heterogeneity between studies examined by subgroup and random effects meta-regression analyses considering patient-related and study-level variables. The pooled estimate showed that β-blocker treatment [among 164 408 (86.8%) patients, with median follow-up time of 2.7 years] was associated with a 26% reduction in all-cause mortality [rate ratio (RR) 0.74, 95% confidence interval (CI) 0.64-0.85] with moderate heterogeneity (I2 = 67.4%). The patient-level variable mean age of the cohort explained 31.5% of between study heterogeneity. There was presence of publication bias, or small study effect, and when controlling for bias by the trim and fill simulation method, the effect disappeared (adjusted RR 0.90, 95% CI 0.77-1.04). Also, small study effect was demonstrated by a cumulative meta-analysis starting with the largest study showing no effect, with increasing effect as the smaller studies were accumulated.
Evidence from this study suggests that there is no association between β-blockers and all-cause mortality. A possible beneficial effect in AMI survivors needs to be tested by large randomized clinical trials.
急性心肌梗死(AMI)后β受体阻滞剂治疗的指南是基于再灌注和二级预防治疗实施前进行的研究。我们旨在评估在心力衰竭和/或左心室射血分数降低发生率低的当代 AMI 后患者中,口服β受体阻滞剂对死亡率的影响。
使用随机效应模型综合了 2000 年 1 月 1 日至 2017 年 10 月 30 日期间发表的 16 项观察性研究的结果。评估了发表偏倚,并通过亚组和随机效应荟萃回归分析,考虑患者相关和研究水平的变量,检查研究之间的异质性。汇总估计表明,β受体阻滞剂治疗(在 164408 名[86.8%]患者中,中位随访时间为 2.7 年)与全因死亡率降低 26%相关[风险比(RR)0.74,95%置信区间(CI)0.64-0.85],存在中度异质性(I2=67.4%)。队列中患者水平变量的平均年龄解释了研究间异质性的 31.5%。存在发表偏倚或小样本效应,并且通过 Trim and Fill 模拟方法控制偏倚时,该效应消失(调整 RR 0.90,95%CI 0.77-1.04)。此外,通过从最初没有效果的最大研究开始的累积荟萃分析也证明了小样本效应,随着较小研究的累积,效果逐渐增加。
本研究的证据表明,β受体阻滞剂与全因死亡率之间没有关联。需要通过大型随机临床试验来检验 AMI 幸存者中是否存在有益作用。