Outcome data.

Background
Haloperidol is a commonly used antipsychotic drug and a frequent source of medication safety alerts because of its listing as a “known risk” QT interval-prolonging medication (QTPmed). We aimed to summarize the high-quality literature on the frequency and nature of proarrhythmic major adverse cardiac events (MACE) associated with haloperidol.
Methods
We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central for randomized controlled trials (RCTs) involving patients 18 years or older comparing haloperidol to placebo. The FDA-adapted MACE composite included death, non-fatal cardiac arrest, ventricular tachyarrhythmia including torsades de pointes, and seizure or syncope. Random-effects meta-analyses were performed with a treatment-arm continuity correction for single and double zero event studies.
Results
84 RCTs (n = 12180, 46% female), 23.8% of trials reported mean or median ages of their participants to be older than 65 years with 37 (44.0%) involving participants with psychiatric diagnoses, and 50 (59.5%) including electrocardiograms. Median follow-up duration was 28.0 days (interquartile range [IQR]=51.0). There were 1144 events, of which 97.8% were deaths, with 22 ventricular arrhythmias and 3 seizures or syncope. There was no difference in MACE with exposure to haloperidol compared to placebo (risk ratio [RR] 0.93, 95% CI: 0.80–1.08; I2 = 0%). IV haloperidol was not associated with increased risk of mortality (n = 5873, RR: 0.88, 95%CI:0.72–1.08).
Conclusions
We did not find that haloperidol was arrhythmogenic or increased mortality in these largely short-duration trials. Further research to clarify actual clinical outcomes related to QTPmeds is important to inform safe prescribing practices.

背景
氟哌啶醇（Haloperidol）是临床常用抗精神病药物，因其被列为“已知风险”QT间期延长药物（QT interval-prolonging medication, QTPmed），常成为药物安全警报的频发来源。本研究旨在总结与氟哌啶醇相关的致心律失常性主要不良心血管事件（major adverse cardiac events, MACE）的发生频率与特征。

方法
本研究检索了Medline、Embase、国际药学文摘（International Pharmaceutical Abstracts）及Cochrane中心数据库，纳入对比氟哌啶醇与安慰剂、纳入18岁及以上受试者的随机对照试验（randomized controlled trials, RCTs）。经美国食品药品监督管理局（FDA）调整的MACE复合终点包括死亡、非致命性心搏骤停、包括尖端扭转型室速（torsades de pointes）在内的室性快速性心律失常，以及癫痫发作或晕厥。针对零事件及单零事件研究，采用随机效应meta分析并进行治疗组连续性校正。

结果
共纳入84项随机对照试验，涉及12180例受试者（46%为女性）；其中23.8%的试验报告受试者的平均或中位年龄≥65岁，37项试验（占比44.0%）纳入存在精神疾病诊断的受试者，50项试验（占比59.5%）纳入了心电图检查。中位随访时长为28.0天（四分位间距[interquartile range, IQR]=51.0）。共计发生1144例不良事件，其中97.8%为死亡事件，另有22例室性心律失常事件及3例癫痫发作或晕厥事件。与安慰剂组相比，氟哌啶醇暴露组的主要不良心血管事件发生风险无显著差异（风险比[risk ratio, RR]=0.93，95%置信区间[confidence interval, CI]：0.80~1.08；I²=0%）。静脉输注氟哌啶醇未增加死亡风险（n=5873，RR=0.88，95%CI：0.72~1.08）。

结论
在这些大多为短期随访的试验中，未发现氟哌啶醇具有致心律失常作用或增加死亡风险。进一步研究明确QT间期延长药物相关的真实临床结局，对指导临床安全处方实践具有重要意义。