Major Adverse Cardiac Events with Ondansetron: A Systematic Review

Ondansetron frequently triggers medication safety alerts because of its listing as a 'known risk' QT interval-prolonging medication. We aimed to summarize literature on QT-prolongation-related major adverse cardiac events associated with ondansetron. We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central for randomized controlled trials comparing ondansetron to placebo in adults. Major adverse cardiac events (MACE) included death, nonfatal cardiac arrest, ventricular tachyarrhythmia including torsades de pointes, seizure, or syncope. Random-effects meta-analyses were performed with a treatment arm continuity correction for single- and double-zero event studies. We included 170 randomized trials (n = 23,421, 70.7% female, 48.3% aged >65), 119 trials (70.0%) involving surgical patients, and 77 (45.4%) including electrocardiograms. Mean follow-up was 10 days (SD: 21.8) (median: 1 day). Risk of bias was high for 11.8% of trials, and low for 28.8%. Only seven MACE (all deaths) were reported. Ondansetron was not associated with increased mortality (n = 23,421, RR: 1.03, 95% CI: 0.76-1.39, I² = 0.0%), or arrhythmias. Lack of events precluded prespecified meta-analyses. Further research on QT-prolonging medications and their attributed adverse cardiac events and medication alert optimization is needed.