Role of Macrolide Antibiotics in Increasing Cardiovascular Risk

Study Questions:

Is there an association between macrolide antibiotics and any of the following: sudden cardiac death (SCD), ventricular tachyarrhythmias (VTAs), cardiovascular death, or death from any cause?


The authors performed a literature search using MEDLINE and EMBASE with no restrictions. Studies reporting relative risk estimates with 95% confidence intervals for the associations of interest were included.


The authors identified 33 studies involving 20,779,963 individuals. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (relative risk [RR], 2.42), SCD (RR, 2.52), and cardiovascular death (RR, 1.31). There was no association between macrolide use and all-cause death or any cardiovascular events. Treatment with macrolides was associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses.


Administration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death, but not increased all-cause mortality.


Over a decade ago, patients with coronary artery disease were randomized to azithromycin vs. placebo with the hope that the macrolide antibiotic would lower adverse cardiac outcomes, which it failed to do. Since then, an increasing number of studies have reported the association of this and other antibiotics on ventricular arrhythmias and sudden death. The present study is a comprehensive analysis of the published literature and points to a small, but due to the prevalence of macrolide administration, significant increase in SCD, VTA, and cardiovascular death. The putative mechanism is block of the Ikr and prolongation of the QT interval. In the analysis, roxithromycin, a macrolide antibiotic not available in the United States, was the only agent not associated with increased SCD, VTA, and cardiovascular death. Further studies should focus on the identification of the clinical profile of patients who experience the increased risk.

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