Wong Angel Y S, Chan Esther W, Anand Shweta, Worsley Alan J, Wong Ian C K
Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Research Department of Practice and Policy, School of Pharmacy, University College London, 9-39 Brunswick Square, London, WC1N 1AX, UK.
Drug Saf. 2017 Aug;40(8):663-677. doi: 10.1007/s40264-017-0533-2.
It was postulated that antibiotics including macrolides could be used for the secondary prevention of coronary heart disease but recent studies showed that macrolides increase the cardiovascular risk. We aimed to review the evidence of cardiovascular risk associated with macrolides regarding duration of effect and risk factors; and to explore the potential effect of statins for the prevention of cardiovascular events as a result of macrolide use.
Several electronic databases (PubMed, EMBASE, Cochrane library) were searched to identify eligible studies. Observational studies and randomized controlled trials that investigated the association between macrolides and cardiovascular events in adults aged ≥18 years were included. A meta-analysis was conducted to investigate the short- and long-term risks of cardiovascular mortality, myocardial infarction, arrhythmia, and stroke. Methodological quality was assessed by the Newcastle-Ottawa scale and the Cochrane Collaboration's tool. The body of evidence was evaluated by the Grading of Recommendations Assessment, Development, and Evaluation guidelines.
Observational studies were found to have a short-term risk of cardiovascular outcomes including cardiovascular mortality, myocardial infarction, and arrhythmia associated with macrolides but no risk was found in randomized controlled trials. However, no association for long-term risk (ranging from >30 days to >3 years) was observed in observational studies or randomized controlled trials.
The included studies reported different units of denominators for absolute risk and used different outcome definitions, which might increase the heterogeneity.
More studies are required to investigate the short-term cardiovascular outcomes associated with different types of macrolides. Future studies are warranted to evaluate the effect of statins for preventing excess acute cardiovascular events associated with clarithromycin or other macrolides.
曾有假设认为，包括大环内酯类抗生素在内的抗生素可用于冠心病的二级预防，但近期研究表明，大环内酯类抗生素会增加心血管疾病风险。我们旨在回顾与大环内酯类抗生素相关的心血管疾病风险在作用持续时间和风险因素方面的证据；并探讨他汀类药物对预防因使用大环内酯类抗生素而导致的心血管事件的潜在作用。
检索了多个电子数据库（PubMed、EMBASE、Cochrane图书馆）以识别符合条件的研究。纳入了调查≥18岁成年人中，大环内酯类抗生素与心血管事件之间关联的观察性研究和随机对照试验。进行了一项荟萃分析，以调查心血管死亡率、心肌梗死、心律失常和中风的短期和长期风险。采用纽卡斯尔-渥太华量表和Cochrane协作组的工具评估方法学质量。依据推荐分级的评估、制定和评价指南对证据体进行评估。
观察性研究发现，大环内酯类抗生素存在导致心血管结局的短期风险，包括心血管死亡率、心肌梗死和心律失常，但随机对照试验未发现此类风险。然而，在观察性研究或随机对照试验中，均未观察到长期风险（范围从>30天至>3年）的关联。
纳入的研究报告的绝对风险分母单位不同，且使用了不同的结局定义，这可能会增加异质性。
需要更多研究来调查与不同类型大环内酯类抗生素相关的短期心血管结局。未来的研究有必要评估他汀类药物对预防与克拉霉素或其他大环内酯类抗生素相关的急性心血管事件过多发生的作用。
