Individuals receiving hemodialysis have high incidence of sudden cardiac death and are susceptible to QT interval prolonging medication-related cardiac complications. Ondansetron, an antiemetic with known QT prolonging potential, is associated with fatal arrythmias in the general population when administered intravenously. The cardiac safety of ondansetron in the hemodialysis population is unknown.

We conducted a new-user, active-comparator, cohort study using US Renal Data System data (2012-2019) to examine the association between the initiation of oral ondansetron vs. antiemetics with lesser QT prolonging potential (promethazine, metoclopramide or prochlorperazine) and the 10-day risk of sudden cardiac death among individuals receiving hemodialysis. We used inverse probability of treatment weighted survival models to estimate adjusted hazard ratios (aHRs), risk differences (aRDs), and 95% confidence intervals (CIs). We used an intention-to-treat approach in which non-sudden cardiac death was considered a competing event. We examined additional cardiac outcomes in secondary analyses.

Of the 119,254 study patients, 64,978 (54.5%) initiated ondansetron, and 54,276 (45.5%) initiated a comparator antiemetic. Initiation of ondansetron versus a comparator antiemetic was associated with higher relative and absolute 10-day risks of sudden cardiac death, aHR (95% CI) = 1.44 (1.08, 1.93); aRD (95% CI) = 0.06% (0.01%, 0.11%). The number needed to harm was 1,688. Analyses of additional cardiac outcomes yielded similar findings.

Compared with initiation of antiemetics with lesser QT prolonging potential, initiation of ondansetron was associated with higher short-term cardiac risks among people receiving hemodialysis.