Cardiac events after macrolides or fluoroquinolones in patients hospitalized for community-acquired pneumonia: post-hoc analysis of a cluster-randomized trial

Background Guidelines recommend macrolides and fluoroquinolones in patients hospitalized with community-acquired pneumonia (CAP), but their use has been associated with cardiac events. Objective To quantify associations between macrolide and fluoroquinolone use and cardiac events in patients hospitalized with CAP in non-ICU wards. Design Post-hoc analysis of a cluster-randomized trial Setting Six hospitals in the Netherlands Patients CAP patients admitted to non-ICU wards and without a cardiac event on admission Measurements Cause-specific hazard ratio’s (HR’s) were calculated for effects of time-dependent macrolide and fluoroquinolone exposure on cardiac events, defined as occurrence of new or worsening heart failure, arrhythmia, or myocardial ischemia during hospitalization. Results Cardiac events occurred in 146 (6.9%) of 2,107 patients and included episodes of heart failure (n=101, 4.8%), arrhythmia (n=53, 2.5%), and myocardial ischemia (n=14, 0.7%). Cardiac events occurred in 11 of 207 (5.3%), 18 of 250 (7.2%), and 31 of 277 (11.2%) patients exposed to azithromycin, clarithromycin, and erythromycin for at least one day, respectively, and in 9 of 234 (3.8%), 5 of 194 (2.6%), and 23 of 566 (4.1%) patients exposed to ciprofloxacin, levofloxacin, and moxifloxacin, respectively. Hazard ratios for any cardiac event, adjusted for confounding, were 0.89 (95% confidence interval (CI) 0.48 to 1.67), 1.06 (95% CI 0.61 to 1.83) and 1.68 (95% CI 1.07 to 2.62) for azithromycin, clarithromycin, and erythromycin, respectively, and adjusted hazard ratios were 0.86 (95% CI 0.47 to 1.57), 0.42 (95% CI 0.18 to 0.96) and 0.62 (95% CI 0.39 to 0.99) for ciprofloxacin, levofloxacin, and moxifloxacin, respectively. Erythromycin was associated with an adjusted hazard ratio of 2.08 (95% CI 1.25 to 3.46) for heart failure. Limitations Possibility of confounding by indication and observational bias Conclusions Among patients with CAP hospitalized to non-ICU wards, erythromycin use was associated with a 68% increased risk of hospital-acquired cardiac events, mainly heart failure. Levofloxacin and moxifloxacin were associated with a lower risk of heart failure. Registration The original trial was registered under ClinicalTrials.gov Identifier [NCT01660204][1] Funding Source The Netherlands Organization for Health Research and Development (ZONmw, Health care efficiency research, project id: 171202002). [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01660204&atom=%2Fbiorxiv%2Fearly%2F2017%2F02%2F14%2F108407.atom