Ondansetron and the Risk of Sudden Cardiac Death among Individuals Receiving Maintenance Hemodialysis

Abstract

Key Points:

1. In hemodialysis, ondansetron initiation versus initiation of lesser QT-prolonging antiemetics associated with higher 10-day sudden cardiac death risk.

2. Analyses considering additional cardiac outcomes had consistent findings.

Background: Individuals receiving hemodialysis have a 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 arrhythmias in the general population when administered intravenously. The cardiac safety of ondansetron in the hemodialysis population is unknown.

Methods: We conducted a new-user, active-comparator, cohort study using United States Renal Data System data (2012–2019) to examine the association between the initiation of oral ondansetron versus 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, risk differences, 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.

Results: Of 119,254 study patients, 64,978 (55%) initiated ondansetron and 54,276 (45%) 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 (adjusted hazard ratio, 1.44 [95% CI, 1.08 to 1.93]; adjusted risk difference, 0.06% [95% CI, 0.01% to 0.11%]). The number needed to harm was 1688. Analyses of additional cardiac outcomes yielded similar findings.

Conclusions: 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.

Graphical abstract

Figure 1

Study design. The figure depicts how new users of study antiemetics were identified. We identified patients meeting study selection criteria who initiated ondansetron or a comparator antiemetic (promethazine, metoclopramide, or prochlorperazine) after a 30-day washout period free of prescription fills for any of the study antiemetic drugs. The index date was defined as the date of study antiemetic initiation. Baseline covariates were identified in the 180 days before the index date, and follow-up began on the index date.

Figure 2

Ten-day risk of sudden cardiac death among patients initiating ondansetron versus comparator antiemetic. The figure shows the 10-day risk of sudden cardiac death among people receiving hemodialysis who initiated ondansetron versus a comparator antiemetic. CI, confidence interval; HR, hazard ratio; RD, risk difference.

Figure 3

Association between the initiation of ondansetron versus comparator antiemetic and the 10-day risk of sudden cardiac death within clinically relevant subgroups. The figure depicts the association between the initiation of ondansetron versus initiation of a comparator antiemetic and the 10-day risk of sudden cardiac death within clinically relevant subgroups. For each subgroup, we estimated subgroup-specific propensity scores and associated IPT weights to control for confounding analogous to the primary analysis. The adjusted (i.e., weighted) subdistribution HRs are adjusted for patient demographics, dialysis characteristics, comorbid conditions, and relevant medication use, among other factors (see Supplemental Table 6 for a comprehensive list of variables used in the propensity score models). aHR, adjusted hazard ratio; IPT, inverse probability of treatment; TdP, Torsades de Pointes.