Azithromycin Exposure in a 10-Day Window of Myocardial Infarction and Short- and Long-Term Outcomes

Background: The U.S. Food and Drug Administration warned in 2012 that azithromycin (AZM) can cause potentially fatal irregular heart rhythm, particularly in patients with known cardiac risk factors. Objectives: This study aimed to examine cardiac and hospital readmission outcomes associated with AZM exposure near the time of a myocardial infarction (MI). Methods: This was a retrospective cohort study using Merative MarketScan databases examining adult inpatients admitted with MI from January 1, 2010 to December 31, 2017. Patients with AZM exposure 7 days pre-MI to 3 days post-MI were compared to unexposed controls. Time to subsequent MI and incident heart failure (HF) were examined up to 5 years post-MI using Cox models. All-cause, MI-related, MI and sequelae-related readmissions and incident HF diagnosis were examined 30 days post-MI using logistic regression. Results: There were 18,066 eligible patients in the full cohort (AZM, N = 3,011), and the HF-free at baseline cohort included 9,180 patients (AZM, N = 1,530). Probability of subsequent MI up to 5 years post-MI was 15.3% in the AZM group vs 9.7% in control (HR: 1.41 [95% CI: 1.10-1.81], P = 0.0076). Probability of incident HF was 39.8% in the AZM group vs 35.5% in control (HR: 1.12 [95% CI: 0.91-1.39], P = 0.2795). Odds of all 4 30-day outcomes were significantly higher in the AZM group vs control. Conclusions: We found an increased risk of long-term subsequent MI, 30-day hospital readmissions, and 30-day incident HF among MI patients with AZM exposure compared to controls. Our findings are consistent with the 2012 Food and Drug Administration warning.