Domperidone and the Risks of Sudden Cardiac Death and Ventricular Arrhythmia: A Systematic Review and Meta-Analysis of Observational Studies.

Aims Concerns exist regarding the cardiovascular safety of domperidone. However, many of the previous studies addressing this issue had important limitations. We aimed to examine domperidone and the risks of sudden cardiac death and ventricular arrhythmia through a systematic review and meta-analysis of observational studies, including an in-depth methodological assessment. Methods We systematically searched MEDLINE, PubMed, EMBASE, Scopus, and CINAHL Plus to identify observational studies examining the association of domperidone and sudden cardiac death and/or ventricular arrhythmia. We assessed study quality in duplicate using the ROBINS-I tool supplemented by an assessment of specific biases and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. Data were pooled across studies using DerSimonian and Laird random-effects models. Results Six case-control studies, one case-crossover study, and one retrospective cohort study were included (n: 480,395). Based on ROBINS-I, three studies had moderate risk of bias, four had serious risk, and one had critical risk. The overall GRADE rating is moderate. When data were pooled across non-overlapping studies, domperidone was associated with an increased risk of composite endpoint of sudden cardiac death or ventricular arrhythmia compared to non-use (adjusted odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.46, 1.95; I2 : 0%; τ2 : 0). This association persisted when restricted to higher-quality studies (OR: 1.60; 95% CI: 1.30, 1.97; I2 : 0%; τ2 : 0). Conclusions Domperidone is associated with an increased risk of sudden cardiac death and ventricular arrhythmia compared to non-use. Further investigation comparing domperidone to an active comparator and in younger populations are warranted.