Azithromycin and cardiovascular risk

Does azithromycin increase cardiovascular (CV) risk? A recent observational study showed that azithromycin was associated with a 2-3 times higher risk of death from CV disease in patients at high risk for CV disease (N Engl J Med 2012;366:1881-1890). A new study looks at the risk of the drug vs placebo and a comparator antibiotic (penicillin V) in Danish adults ages 18-64. As compared with no use of antibiotics, use of azithromycin was associated with a significantly increased risk of CV death (rate ratio 2.85; 95% CI, 1.13-7.24); however, when compared to penicillin V, there was no increased risk (crude rate CV death 1.1/1000 person years azithromycin vs 1.5/1000 penicillin V). With adjustment for CV risk, current azithromycin use was not associated with increased risk of CV death compared with penicillin V in a general population of young and middle-aged adults. (N Engl J Med 2013;368:1704-1712). This study is reassuring, suggesting that the increased risk of death is probably due to the illness rather than the drug, especially in low-risk populations. However, the risk of the macrolides still should be considered among patients with a high baseline risk of CV disease.