Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Pharmacovigilance Department, Ministry of Health, Jerusalem, Israel.
Antimicrob Agents Chemother. 2018 May 25;62(6). doi: 10.1128/AAC.00438-18. Print 2018 Jun.
Studies reporting an increased risk for cardiac toxicities with macrolide antibiotics have raised concern regarding their cardiovascular safety. We sought to assess the cardiac safety of macrolide antibiotics as a class and of the individual agents by conducting a systematic review and network meta-analysis. Medline, Embase, and the Cochrane Library were searched up to February 2018 for studies reporting on cardiovascular outcomes with macrolides. We followed the PRISMA 2009 guidelines for data selection and extraction. Outcomes were pooled using random-effects models and odds ratios (OR), and 95% confidence intervals (CI) were calculated for arrhythmia, cardiovascular death, and myocardial infarction (MI). A total of 33 studies and data on 22,601,032 subjects were retrieved and included in the current meta-analyses. Macrolide use was not associated with the risk of arrhythmia or cardiovascular mortality. In the primary analysis, macrolide use was associated with a small but statistically significant 15% increase in risk for MI (OR = 1.15 [95% CI, 1.01 to 1.30]). In indirect network meta-analysis, erythromycin and clarithromycin were ranked considerably more likely to be associated with a higher risk for MI and significantly associated with increased risk of MI compared to azithromycin (OR = 1.58 [95% CI, 1.18 to 2.11] and OR = 1.41 [95% CI, 1.11 to 1.81], respectively). Our findings indicate that macrolide antibiotics as a group are associated with a significant risk for MI but not for arrhythmia and cardiovascular mortality. Among the macrolides, erythromycin and clarithromycin were associated with a greater risk of MI. However, it is possible that the association between macrolide use and risk of MI is the result of residual confounding.
研究报告称，使用大环内酯类抗生素会增加心脏毒性的风险，这引起了人们对其心血管安全性的关注。我们旨在通过系统评价和网络荟萃分析评估大环内酯类抗生素作为一类药物以及个别药物的心脏安全性。我们检索了 Medline、Embase 和 Cochrane 图书馆，以获取截至 2018 年 2 月关于大环内酯类药物心血管结局的研究报告。我们遵循 PRISMA 2009 指南进行数据选择和提取。使用随机效应模型和比值比（OR）汇总结果，并计算心律失常、心血管死亡和心肌梗死（MI）的 OR 和 95%置信区间（CI）。共检索到 33 项研究和 22601032 名受试者的数据，并纳入当前的荟萃分析。大环内酯类药物的使用与心律失常或心血管死亡率的风险无关。在主要分析中，大环内酯类药物的使用与 MI 风险增加 15%（OR = 1.15 [95%CI，1.01 至 1.30]）相关，但具有统计学意义。在间接网络荟萃分析中，红霉素和克拉霉素与 MI 风险增加相关的可能性明显更大，与阿奇霉素相比，与 MI 风险显著相关（OR = 1.58 [95%CI，1.18 至 2.11] 和 OR = 1.41 [95%CI，1.11 至 1.81]）。我们的研究结果表明，大环内酯类抗生素作为一类药物与 MI 风险显著相关，但与心律失常和心血管死亡率无关。在大环内酯类药物中，红霉素和克拉霉素与 MI 风险增加相关。然而，大环内酯类药物使用与 MI 风险之间的关联可能是残余混杂的结果。
