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-1; 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.

中文翻译：

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伊伐布雷定对危重患者的主要不良心血管事件和死亡率的影响：随机对照试验的系统评价和荟萃分析，并进行试验顺序分析。

背景技术伊伐布雷定在不影响收缩力或血管张力的情况下降低心率（HR）。它被许可用于慢性心脏病的HR控制。我们进行了系统的回顾和荟萃分析，以检查伊伐布雷定是否可以降低危重患者的主要不良心血管事件（MACE）和死亡率。方法我们在Medline，Embase，Cochrane图书馆和Web of Science中搜索了RCT。使用Cochrane偏倚风险工具评估审判质量。如果至少有3个试验或100名患者可用，则进行随机效应荟萃分析。结果报告为加权平均差（WMD），优势比（OR）和95％置信区间（CIs）。进行了试验性顺序分析，以估计达到功效或无效性的明确结论所需的样本量。结果我们纳入了13项RCT（n = 1497例患者）。我们没有发现伊伐布雷定对MACE有影响的证据（3个RCT，819例患者; OR = 0.77; 95％CI，0.53-1.11）或死亡率（10个RCT，1356例患者; OR = 1.07; 95％CI，0.63-1.82） ），但没有得出样本数量以得出明确的结论。与安慰剂或标准治疗相比，伊伐布雷定可降低HR（8个RCT，464例患者； WMD，-9.5次min-1； 95％CI，-13.3至-5.8）。伊伐布雷定和对照组之间发生心动过缓的风险没有差异（五个RCT，434例患者； OR = 1.2； 95％CI，0.60-2.38）。总体上偏见风险很高或不清楚。结论与安慰剂或标准治疗相比，伊伐布雷定可降低HR。急性护理对MACE或死亡率的影响尚不清楚。还需要进一步的RCT，以检测临床相关结果的变化。