Risk of Cardiac Events With Azithromycin, Amoxicillin Compared

The aim of the study was to use real-world data to compare the risk of cardiac events in new users of azithromycin vs amoxicillin.

Azithromycin does not appear to increase the risk of cardiac events when compared with amoxicillin, except for when QT-prolonging medications are used concurrently, according to the findings of a recently published retrospective cohort study.

The aim of the study was to use real-world data to compare the risk of cardiac events in new users of azithromycin vs amoxicillin. The study authors searched the Truven Health Analytics MarketScan database between January 1, 2009, and June 30, 2015 for data on patients who were enrolled in a health care plan 365 days prior to (baseline period) the dispensing date (index date) of receiving either amoxicillin or azithromycin. High-dimensional propensity scores were used to match the patients 1:1.

“The primary outcome consisted of cardiac events, including syncope, palpitations, ventricular arrhythmias, cardiac arrest, or death as a primary diagnosis for hospitalization at 5, 10, and 30 days from the index date,” the study authors explained. Odds ratios (ORs) were estimated using logistic regression models.

A total of 2,141,285 episodes of each index therapy (N=4,282,570) were included in the final cohort after matching. The average (SD) age of patients in the cohort was 35.7 (22.3) years old and 52.6% of the patients were female. The study authors reported that a total of 1474 cardiac events (0.03%) occurred within 5 days of initiation of therapy, with 708 events occurring in the amoxicillin group and 766 events occurring in the azithromycin group. Syncope (n=1032; 70.0%) and palpitations (n=331; 22.5%) were the 2 most frequent cardiac events.

Findings of the study revealed that the risk of cardiac events was not significantly higher for patients who received azithromycin vs amoxicillin at 5 days (OR, 1.08; 95% CI, 0.98-1.20), 10 days (OR, 1.05; 95% CI, 0.97-1.15), or 30 days (OR, 0.98; 95% CI, 0.92-1.04). Data analysis did reveal, however, that there was an increased risk of cardiac events among patients who were concomitantly taking a QT-prolonging medication with azithromycin compared with amoxicillin (OR, 1.40; 95% CI, 1.04-1.87). The study authors also reported numerically higher odds of cardiac events with azithromycin in patients over 65 years and in those with a history of cardiovascular disease or other risk factors; however, none of these associations were found to be statistically significant.

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“This study found no association of cardiac events with azithromycin compared with amoxicillin except among patients using other QT-prolonging drugs concurrently,” the study authors concluded. They added, “Although azithromycin is a safe therapy, clinicians should carefully consider its use among patients concurrently using other QT-prolonging drugs.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Haridarshan P, Calip GS, DiDomenico RJ, Schumock GT, Suda KJ, Lee TA. Comparison of cardiac events associated with azithromycin vs amoxicillin [published online September 15, 2020]. JAMA Network Open. 2020;3(9):e2016864. doi:10.1001/jamanetworkopen.2020.16864.