Long Term Risk of Cardiovascular Death With Use of Clarithromycin and Roxithromycin – a Nationwide Cohort Study

Abstract

Recent studies have raised concern that macrolide antibiotics may be associated with a long-term increased risk of cardiovascular death. This study examines the one-year risk associated with treatment with clarithromycin (n = 751,543) and roxithromycin (n = 698,899) compared with penicillin V (n = 2,721,538), matched 1:4 on propensity score, in a nationwide registry-based cohort study in Danish outpatients, 1997–2011. Among clarithromycin courses, the rate ratio (RR) of cardiovascular death was 1.24; 95% CI: 0.96, 1.59). Among roxithromycin courses, the RR was 0.99 (0.86, 1.16). In analyses by time after treatment start, the RR associated with clarithromycin was 1.66 (0.98, 2.79) during days 0–7; this was attenuated in later time periods, RR days 8–89: 1.30 (0.88, 1.94) and RR days 90–364: 0.96 (0.63, 1.47). For roxithromycin, the RRs were 0.88 (0.59, 1.32) during days 0–7, 1.17 (0.92, 1.48) during days 8–89 and 0.88 (0.70, 1.10) during days 90–364. This study found no increased risk of cardiovascular death in a general outpatient population. With clarithromycin, we observed a transient increased risk during days 0–7 after treatment start, which corresponds to the period of active treatment. This association was absent in later time periods, which is consistent with no long-term toxicity resulting in cardiovascular death.