Department of Pharmacy Practice and Science, University of Iowa, Iowa City, IA
Department of Biostatistics, University of Iowa, Iowa City, IA.
J Am Heart Assoc. 2018 Apr 21;7(9):e008074. doi: 10.1161/JAHA.117.008074.
Some studies have found that antimicrobials, especially macrolides, increase the risk of cardiovascular death. We investigated potential cardiac-related events associated with antimicrobial use in a population of patients with acute myocardial infarction.
For 185 010 Medicare beneficiaries, we recorded prescriptions for azithromycin, clarithromycin, levofloxacin, moxifloxacin, doxycycline, and amoxicillin-clavulanate. In the following week, we recorded death, acute myocardial infarction, atrial fibrillation or atrial flutter, a non-atrial fibrillation/atrial flutter arrhythmia, or ventricular arrhythmia. We fit unadjusted and adjusted logistic regression models using generalized estimating equations. Adjusted models included patients' comorbidities, medications, procedures, demographics, insurance status, time since index acute myocardial infarction, number of visits, and the influenza rate. In unadjusted analyses, macrolides and fluoroquinolones were associated with a risk of cardiac events. However, the risk associated with macrolide use was substantially attenuated after adjustment for a wide range of variables, and the risk associated with fluoroquinolones was no longer statistically significant. For example, for azithromycin, the odds ratio for any cardiac event or death was 1.35 (95% confidence interval, 1.27-1.44; <0.0001), but after controlling for a wide range of covariates, the odds ratio decreased to 1.01 (95% confidence interval, 0.95-1.08; <0.6688).
Controlling for covariates explains much of the adverse cardiac risk associated with antimicrobial use found in other studies. Most antimicrobials are not associated with risk of cardiac events, and others, specifically azithromycin and clarithromycin, may pose a small risk of certain cardiac events. However, the modest potential risks attributable to these antimicrobials must be weighed against the drugs' considerable and immediate benefits.
一些研究发现，抗菌药物，尤其是大环内酯类药物，会增加心血管死亡的风险。我们研究了在急性心肌梗死患者人群中使用抗菌药物与潜在心脏相关事件之间的关系。
对于 185010 名医疗保险受益人群，我们记录了阿奇霉素、克拉霉素、左氧氟沙星、莫西沙星、多西环素和阿莫西林克拉维酸的处方。在接下来的一周内，我们记录了死亡、急性心肌梗死、心房颤动或心房扑动、非心房颤动/心房扑动性心律失常或室性心律失常。我们使用广义估计方程拟合未经调整和调整后的逻辑回归模型。调整后的模型包括患者的合并症、药物、程序、人口统计学、保险状况、从指数急性心肌梗死到现在的时间、就诊次数和流感发生率。在未经调整的分析中，大环内酯类和氟喹诺酮类与心脏事件风险相关。然而，在调整了广泛的变量后，大环内酯类药物使用与风险的相关性显著减弱，而氟喹诺酮类药物与风险的相关性不再具有统计学意义。例如，对于阿奇霉素，任何心脏事件或死亡的比值比为 1.35（95%置信区间，1.27-1.44；<0.0001），但在控制了广泛的混杂因素后，比值比降至 1.01（95%置信区间，0.95-1.08；<0.6688）。
控制混杂因素解释了其他研究中发现的与抗菌药物使用相关的大部分不良心脏风险。大多数抗菌药物与心脏事件风险无关，而其他抗菌药物，特别是阿奇霉素和克拉霉素，可能会增加某些心脏事件的风险。然而，这些抗菌药物所带来的适度潜在风险必须与药物的巨大和直接益处相权衡。
