Domperidone and the risks of sudden cardiac death and ventricular arrhythmia: A systematic review and meta-analysis of observational studies

Br J Clin Pharmacol. 2021 Oct;87(10):3649-3658. doi: 10.1111/bcp.14737. Epub 2021 Mar 4.


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, 1 case-crossover study and 1 retrospective cohort study were included (n = 480 395). Based on ROBINS-I, 3 studies had moderate risk of bias, 4 had serious risk, and 1 had critical risk. The overall GRADE rating is moderate. When data were pooled across nonoverlapping studies, domperidone was associated with an increased risk of composite endpoint of sudden cardiac death or ventricular arrhythmia compared to nonuse (adjusted odds ratio: 1.69; 95% confidence interval: 1.46, 1.95; I2 : 0%; τ2 : 0). This association persisted when restricted to higher-quality studies (odds ratio: 1.60; 95% confidence interval: 1.30, 1.97; I2 : 0%; τ2 : 0).

Conclusion: Domperidone is associated with an increased risk of sudden cardiac death and ventricular arrhythmia compared to nonuse. Further investigation comparing domperidone to an active comparator and in younger populations are warranted.

Keywords: cardiovascular safety; domperidone; meta-analysis; observational studies; sudden cardiac death; ventricular arrhythmia.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antiemetics*
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / epidemiology
  • Cross-Over Studies
  • Death, Sudden, Cardiac / epidemiology
  • Death, Sudden, Cardiac / etiology
  • Domperidone* / adverse effects
  • Humans
  • Retrospective Studies


  • Antiemetics
  • Domperidone