Division of Clinical Pharmacy, School of Pharmacy, The Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, 9112001, Jerusalem, Israel.
Department of Pharmacovigilance, Ministry of Health, Jerusalem, Israel.
Drug Saf. 2019 Apr;42(4):529-538. doi: 10.1007/s40264-018-0751-2.
Several fluoroquinolone antibiotics have been associated with cardiac adverse effects, leading to the withdrawal of some of these agents from the market. Cardiac side effects such as QT prolongation and torsades de pointes (TdP) have also been observed with fluoroquinolones currently on the market. In order to evaluate the cardiac risk of fluoroquinolones as a class, and the comparative risk for each individual drug, we conducted a systematic review, meta-analysis, and network meta-analysis.
MEDLINE, EMBASE and the Cochrane Library were searched, up to March 2018, for randomized controlled trials, cohort studies, and case-control studies that investigated the association between fluoroquinolone treatment and the risk of cardiovascular events and cardiovascular mortality. We followed the PRISMA 2009 guidelines for data selection and extraction. Outcomes were pooled using random effects models. Direct and indirect comparisons in network meta-analysis were performed using frequentist methods.
Thirteen studies were included in our analyses. Fluoroquinolone use was associated with a statistically significant 85% increase in the risk for arrhythmia (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.22-2.81) and 71% increase in the risk for cardiovascular mortality (OR 1.71; 95% CI 1.39-2.09). Moxifloxacin ranked most likely to have the highest risk for arrhythmia (P-score 0.99) and for cardiovascular mortality (P-score 0.95) by network meta-analysis.
Our findings show a significant association between fluoroquinolone use and an increased risk for arrhythmia and cardiovascular mortality. Moxifloxacin ranked with the highest probability for cardiovascular adverse events. Further study is required to determine how to reduce the risk for fluoroquinolone-associated cardiac toxicity.
一些氟喹诺酮类抗生素与心脏不良事件有关，导致其中一些药物从市场上撤出。目前市场上的氟喹诺酮类药物也观察到心脏副作用，如 QT 间期延长和尖端扭转型室性心动过速（TdP）。为了评估氟喹诺酮类药物作为一类药物的心脏风险，以及每种药物的相对风险，我们进行了系统评价、荟萃分析和网络荟萃分析。
我们在 MEDLINE、EMBASE 和 Cochrane 图书馆中进行了检索，截至 2018 年 3 月，检索了调查氟喹诺酮类药物治疗与心血管事件和心血管死亡率风险之间关联的随机对照试验、队列研究和病例对照研究。我们遵循 PRISMA 2009 指南进行数据选择和提取。使用随机效应模型汇总结果。在网络荟萃分析中使用频率方法进行直接和间接比较。
我们的分析纳入了 13 项研究。氟喹诺酮类药物的使用与心律失常风险增加 85%（比值比 [OR] 1.85；95%置信区间 [CI] 1.22-2.81）和心血管死亡率风险增加 71%（OR 1.71；95% CI 1.39-2.09）具有统计学意义。网络荟萃分析显示，莫西沙星最有可能具有心律失常（P 评分 0.99）和心血管死亡率（P 评分 0.95）的最高风险。
我们的研究结果表明，氟喹诺酮类药物的使用与心律失常和心血管死亡率风险增加之间存在显著关联。莫西沙星在心血管不良事件中排名最高。需要进一步研究如何降低氟喹诺酮类药物相关心脏毒性的风险。
