伊伐布雷定对危重症患者主要不良心血管事件和死亡率的影响：一项系统评价和随机对照试验荟萃分析，采用试验序贯分析。

Effect of ivabradine on major adverse cardiovascular events and mortality in critically ill patients: a systematic review and meta-analyses of randomised controlled trials with trial sequential analyses.

机构信息

Division of Anaesthesiology, Department of Acute Medicine, Geneva University Hospitals, Switzerland; Perioperative Basic, Translational and Clinical Research Group, Division of Anaesthesiology, Geneva University Hospitals, Geneva, Switzerland.

Division of Anaesthesiology, Department of Acute Medicine, Geneva University Hospitals, Switzerland; Institute of Global Health, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

出版信息

Br J Anaesth. 2020 Jun;124(6):726-738. doi: 10.1016/j.bja.2020.01.027. Epub 2020 Mar 6.

DOI:10.1016/j.bja.2020.01.027

PMID:32147100

Abstract

BACKGROUND

Ivabradine lowers heart rate (HR) without affecting contractility or vascular tone. It is licensed for HR control in chronic heart diseases. We performed a systematic review and meta-analyses to examine whether ivabradine could decrease major adverse cardiovascular events (MACE) and mortality in critically ill patients.

METHODS

We searched Medline, Embase, Cochrane Library, and Web of Science for RCTs. Trial quality was assessed using the Cochrane risk of bias tool. Random-effects meta-analyses were performed if at least three trials or 100 patients were available. Results are reported as weighted mean difference (WMD), odds ratio (OR), and 95% confidence intervals (CIs). Trial sequential analyses were performed to estimate the sample size needed to reach definitive conclusions of efficacy or futility.

RESULTS

We included 13 RCTs (n=1497 patients). We found no evidence of an impact of ivabradine on MACE (three RCTs, 819 patients; OR=0.77; 95% CI, 0.53-1.11) or mortality (10 RCTs, 1356 patients; OR=1.07; 95% CI, 0.63-1.82), but sample sizes were not reached to allow definitive conclusions. Compared with placebo or standard care, ivabradine reduced HR (eight RCTs, 464 patients; WMD, -9.5 beats min; 95% CI, -13.3 to -5.8). Risk of bradycardia was not different between ivabradine and control (five RCTs, 434 patients; OR=1.2; 95% CI, 0.60-2.38). Risk of bias was overall high or unclear.

CONCLUSIONS

Ivabradine reduces HR compared with placebo or standard care. The effect on MACE or mortality in acute care remains unclear. Further RCTs powered to detect changes in clinically relevant outcomes are warranted.

CLINICAL TRIAL REGISTRATION

Prospero CRD42018086109.

摘要

背景

伊伐布雷定可降低心率（HR）而不影响心肌收缩力或血管张力。它在慢性心脏病中被批准用于 HR 控制。我们进行了系统评价和荟萃分析，以检查伊伐布雷定是否可以降低危重病患者的主要不良心血管事件（MACE）和死亡率。

方法

我们检索了 Medline、Embase、Cochrane 图书馆和 Web of Science 中的 RCT。使用 Cochrane 偏倚风险工具评估试验质量。如果至少有三项试验或 100 名患者可用，则进行随机效应荟萃分析。结果以加权均数差（WMD）、比值比（OR）和 95%置信区间（CI）表示。进行试验序贯分析以估计达到疗效或无效结论所需的样本量。

结果

我们纳入了 13 项 RCT（n=1497 名患者）。我们没有发现伊伐布雷定对 MACE（三项 RCT，819 名患者；OR=0.77；95%CI，0.53-1.11）或死亡率（10 项 RCT，1356 名患者；OR=1.07；95%CI，0.63-1.82）有影响的证据，但样本量尚未达到可以得出明确结论的程度。与安慰剂或标准治疗相比，伊伐布雷定降低了 HR（八项 RCT，464 名患者；WMD，-9.5 次/分钟；95%CI，-13.3 至-5.8）。伊伐布雷定与对照组之间的心动过缓风险无差异（五项 RCT，434 名患者；OR=1.2；95%CI，0.60-2.38）。总体偏倚风险较高或不明确。