Macrolide antibiotics may be associated with a small increased risk for cardiovascular complications
While the absolute risks for sudden cardiac death and ventricular tachyarrhythmias were small, macrolides are 1 of the more commonly used antibiotic groups in many countries, and millions of patients are prescribed these drugs annually.
Macrolide antibiotics were associated with increased risk for sudden cardiac death (SCD), ventricular tachyarrhythmia (VTA), and cardiovascular death but not increased all-cause mortality, a meta-analysis found.
The analysis included 33 studies from the literature involving more than 20 million participants. Eleven of the studies (3 randomized controlled trials, 5 cohort studies, and 3 case-control studies) with data for more than 6.6 million people and more than 5,800 events reported risk estimates for SCD or VTA. Twelve studies (6 randomized controlled trials and 6 cohort studies), involving more than 17 million participants and almost 4,200 events, were included for the outcome of cardiovascular death. Results appeared in the Nov. 17/24 Journal of the American College of Cardiology.
Patients taking macrolides, compared with those who took no macrolides, had an increased risk of SCD or VTA (relative risk [RR], 2.42; 95% CI, 1.61 to 3.63), SCD (RR, 2.52; 95% CI, 1.91 to 3.31), and cardiovascular death (RR, 1.31; 95% CI, 1.06 to 1.62). No association was found between macrolides use and all-cause death. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTAs and 38.2 additional cardiovascular deaths per 1 million treatment courses, the authors calculated.
“Interpretation of the clinical importance of this finding is delicate,” they wrote. “The estimates for additional SCDs and cardiac deaths per 1 million treatment courses are remarkably close, suggesting that most VTA observed in the macrolide groups might not result in fatal outcomes. The absolute risks for SCD and cardiac death are small, so this finding should probably have limited effect on prescribing practice in individual patients. However, given that macrolides are 1 of the more commonly used antibiotic groups in many countries and that millions of patients are prescribed these drugs annually, the total number of excess SCD or VTAs and cardiac deaths may not be negligible.”
An editorial noted that “roughly 1:8,500 patients treated with a macrolide antibiotic is expected to develop a serious arrhythmic event, and 1:30,000 could die suddenly, because of our treatment.” However, the editorial continued, other treatments have their own drawbacks, and risks for drug-induced long QT syndromes can be further reduced by screening for well-recognized risk factors. The editorial called for development of guidelines on the topic.