Table_2_Administration of macrolide antibiotics increases cardiovascular risk.DOCX

BackgroundThe increased risk of cardiovascular events in patients prescribed macrolides has been subject to debate for decades. MethodsMedline, EMBASE databases and ClinicalTrials.gov were searched from inception until August 31, 2022 for studies investigating the link between macrolides and cardiovascular risk. A meta-analysis was performed using a random-effects model. ResultsA total of 80 studies involving 39,374,874 patients were included. No association was found between macrolides and all-cause death. However, compared with the non-macrolide group, macrolides were associated with a significantly increased risk of ventricular arrhythmia or sudden cardiac death (VA or SCD) (azithromycin, relative ratio [RR]: 1.53; 95% confidence interval [CI]: 1.19 to 1.97; clarithromycin, RR: 1.52; 95% CI: 1.07 to 2.16). Besides, administration of macrolides was associated with a higher risk of cardiovascular disease (CVD) death (azithromycin, RR: 1.63; 95% CI: 1.17 to 2.27) and a slightly increased risk of myocardial infarction (MI) (azithromycin, RR: 1.08; 95% CI: 1.02 to 1.15). Interestingly, no association was observed between roxithromycin and adverse cardiac outcomes. Increased risk of VA or SCD was observed for recent or current use of macrolides, MI for former use, and CVD death for current use. ConclusionAdministration of macrolide antibiotics and timing of macrolide use are associated with increased risk for SCD or VTA and cardiovascular death, but not all-cause death.背景 数十年来，大环内酯类（macrolides）药物处方患者发生心血管事件的风险升高这一议题始终存在争议。 方法 本研究检索了Medline、EMBASE数据库以及ClinicalTrials.gov平台自建库至2022年8月31日的相关文献，以筛选探讨大环内酯类与心血管风险相关性的研究。本研究采用随机效应模型开展荟萃分析。 结果 本研究共纳入80项研究，涉及39374874例患者。未发现大环内酯类与全因死亡存在相关性。然而，与非大环内酯类药物组相比，大环内酯类药物与室性心律失常（ventricular arrhythmia, VA）或心源性猝死（sudden cardiac death, SCD）风险显著升高相关：阿奇霉素的相对风险比（relative ratio, RR）为1.53，95%置信区间（confidence interval, CI）为1.19~1.97；克拉霉素的相对风险比为1.52，95%置信区间为1.07~2.16。此外，使用大环内酯类药物与心血管疾病（cardiovascular disease, CVD）死亡风险升高相关（阿奇霉素：相对风险比=1.63，95%置信区间=1.17~2.27），同时可轻度升高心肌梗死（myocardial infarction, MI）风险（阿奇霉素：相对风险比=1.08，95%置信区间=1.02~1.15）。值得注意的是，未观察到罗红霉素与不良心脏结局存在相关性。进一步分析显示，近期或当前使用大环内酯类药物与VA/SCD风险升高相关，既往使用大环内酯类药物与MI风险升高相关，而当前使用大环内酯类药物则与CVD死亡风险升高相关。 结论 大环内酯类抗生素的使用及其用药时机与心源性猝死或室性快速性心律失常（ventricular tachyarrhythmia, VTA）、心血管死亡风险升高相关，但与全因死亡无显著关联。