Appraisal of the cardiovascular risks of azithromycin: an observational analysis

To assess the association of cardiovascular mortality in patients prescribed azithromycin compared with patients prescribed alternative antibiotics in an outpatient setting.

This study was a retrospective observational analysis using the South Carolina Medicaid claims and pharmacy databases over the years from 2000 to 2011 housed at the Revenue and Fiscal Affairs Office. Study antibiotics included azithromycin, amoxicillin, clindamycin, clarithromycin and quinolones (levofloxacin, ciprofloxacin and moxifloxacin), and excluded patients at a high risk of death from causes other than the study antibiotics. This study used both matching and regression adjustment with propensity scores to reduce possible bias in the estimated treatment (group) effect from confounders.

The total number of prescriptions evaluated in the study include: 283,743 azithromycin; 143,191 amoxicillin; 52,714 clindamycin; 38,133 clarithromycin and 49,734 for the quinolones. After propensity score weighting, cardiac deaths per million within the first 5 days were: 84.6 for azithromycin, 78.3 for clarithromycin, 69.4 for amoxicillin, 61.6 for quinolones and 15.0 for clindamycin. Our multivariate models reveal that the study antibiotics' (amoxicillin, clindamycin, clarithromycin, levofloxacin, ciprofloxacin and moxifloxacin) mortality rates are not statistically different from azithromycin in any time interval (days: 0-5, 6-10, 0-10 and 0-30). In comparison with previous studies, the results are consistent in Amoxicillin. In the first 5 and 10 days, it is associated with lower odds of cardiovascular death than azithromycin (5 days: odds ratio [OR]: 0.70 [95% CI: 0.25-1.99]; 10 days: OR: 0.92 [95% CI: 0.39-2.14]). However, we find no statistically significant difference between the two antibiotics.

Our study shows that the odds of cardiovascular mortality between azithromycin and other antibiotics are not statistically significantly different and previous published findings may not be applicable to the general population. Additionally our results suggest that while we cannot rule out the increased risk of cardiovascular death from azithromycin in patients at low risk of death, the risk may not be as large initial studies suggest. Further research is needed to define the population at greatest risk.