Current scientific literature presents conflicting evidence regarding the association between the commonly prescribed antibiotic, azithromycin, and the likelihood of cardiac events. As a widely used medication, azithromycin is prescribed over 30 million times per year in the United States and is considered one of the safest antibiotics on the market due to its lower arrhythmogenic activity. However, prior studies have found a potential connection between the medication and cardiovascular events.

Data from a recent study aims to further clarify the relationship between azithromycin and cardiovascular complications by revealing the potentially harmful confounding impact of QT-prolonging medications in patients as compared with amoxicillin use.

Likelihood of Cardiac Events with Amoxicillin v. Azithromycin 

The retrospective cohort published in JAMA Network Open was led by Haridarshan Patel, Pharm.D., Ph.D., from the University of Illinois at Chicago. Researchers analyzed data from the Truven Health Analytics MarketScan database to compare the odds of cardiac events occurring among new users of azithromycin versus amoxicillin.

The study cohort included 4,282,570 patients equally split between therapies. Primary outcomes measured were cardiac events: syncope, palpitations, ventricular arrhythmias, cardiac arrest, or death.

According to their results, researchers reported a total of 1,474 cardiac events occurred within 5 days of initiating therapy, including 708 in the amoxicillin cohort and 766 in the azithrymocin group. The two most frequently reported events were syncope occurring at a rate of 70% and heart palpitations at 22.5%.

Increased Risk Tied to QT-Prolonging Drugs

Although at 5, 10, and 30 days after treatment initiation, the risk for cardiac events was not significantly higher in either cohort, researchers discovered an increased risk in a particular group of patients. The odds of cardiac events in patients receiving concurrent QT-prolonging medications were increased with azithromycin use compared with amoxicillin; patients in this group taking azithromycin were up to 40% more likely to suffer a cardiac event. However, no increased risk was observed with azithromycin use in patients aged 65 years and above or those with a history of cardiovascular disease and other risk factors.

While both antibiotics appear to have a similar threat of cardiac events in the majority of patients, this does not apply to individuals who concurrently use QT-prolonging medications. Clinicians may choose to prescribe amoxicillin or other antibiotics in this subgroup of patients as the latest findings warrant greater caution in the prescription of azithromycin. This is especially relevant now as azithromycin is being investigated as a potential COVID-19 treatment without substantial evidence supporting its benefits against the virus.