A link between azithromycin, one of the most commonly used antibiotics in the United States, and an increased risk of cardiac events has been suggested in some studies. However, research results are conflicting, possibly because of researchers' limited ability to control for key confounders, such as indication for use. In a retrospective cohort study, researchers examined the risk of cardiovascular death and sudden cardiac death associated with the use of azithromycin compared with amoxicillin in a general member population of Kaiser Permanente California.

The study cohort included outpatients 30 to 74 years old who had a prescription for azithromycin or amoxicillin and prescription benefit coverage for at least 12 months prior to the index date (the day the prescription was dispensed). Patients who received more than one study antibiotic were excluded from the study, as were those without prescription coverage on the index date, those hospitalized for the 30 days prior to the index date, those residing in a nursing home for more than 30 days in the year before dispensing, and those who had a serious underlying condition. Propensity scores were used to control for confounding factors.

The study included 7,824,681 antibiotic exposures (1,736,976 to azithromycin and 6,087,705 to amoxicillin) among 2,929,008 individuals.

Patients receiving azithromycin were at approximately twice the risk of cardiovascular death within five days of the index date compared with those receiving amoxicillin. There was no statistically significant difference in risk of sudden cardiac death within five days of the index date. Neither result was significant within six to 10 days of the index date. Azithromycin was also associated with an increased risk of all-cause death and noncardiovascular death within five days but not within six to 10 days of the index date.

The authors point out that causality was not established, and that residual confounding factors are possible, even though they tried to reduce the potential for confounding factors such as indication for use, severity of infection, and underlying comorbidities.