Risk Evaluation and Prediction of Cardiac Events among Azithromycin Users

In the last 30 years, over a billion azithromycin prescriptions have been dispensed since its approval in the US. The drug was once considered the safest macrolide, but ten years after its approval, evidence from case reports suggested a concern cardiac events and eath with its use. In three different studies, we measured the impact of the FDA warning in the use of azithromycin among high-risk patients, identified the baseline predictors of cardiac events among azithromycin users, and compared the risk of cardiac events with azithromycin and amoxicillin users. In the first study, we observed statistically lower prevalence rates of the cardiac risk factors after the FDA warning; however, the absolute prevalence remained similar before and after the warning. In the second study, we identified consistent predictors of the outcome, which included age, sex, history of syncope, cardiac dysrhythmias, non-specific chest pain, and presence of a concurrent QT-prolonging drug. From this list, we created a tool to ease the process of finding patients at a higher risk of cardiac events. In the third study, we evaluated the risk of cardiac events with azithromycin compared to amoxicillin. Using an active comparator, new user design in a large cohort of over 4 million episodes of azithromycin and amoxicillin, we found no increased risk of cardiac events with azithromycin. In sub-group analyses, the risk was 40% higher among patients prescribed concurrent QT-prolonging drugs. The finding of no increased risk was consistent across several other subgroup analyses. We used real-world data to measure the prevalence of cardiac risk factors before and after the FDA warning, quantified the predictors of cardiac risk factors, and evaluated the risk of cardiac risks with azithromycin compared to amoxicillin. We found that there was no change in prevalence of risk factors after the FDA warning, specific baseline patient characteristics put patients treated with azithromycin at a higher risk of cardiac events, and there was an increased risk of cardiac events with azithromycin compared to amoxicillin. Although the risk is rare, providers should avoid the use of QT-prolonging drugs with azithromycin. Future research should focus on examining the risk of cardiac deaths among azithromycin users.