Estimated Cardiac Risk Associated With Macrolides and Fluoroquinolones Decreases Substantially When Adjusting for Patient Characteristics and Comorbidities

Background 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. Methods and Results 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; P <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; P <0.6688). Conclusions 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.