Domperidone increases harmful cardiac events in Parkinson's disease: A Bayesian re-analysis of an observational study

J Clin Epidemiol. 2021 Dec;140:93-100. doi: 10.1016/j.jclinepi.2021.09.002. Epub 2021 Sep 8.

Abstract

Objectives: To assess the risks of ventricular tachyarrhythmia/sudden cardiac death (VT/SCD) with domperidone use in Parkinson's disease (PD).

Study designs and settings: Using Bayesian methods, results from an observationalstudy were combined with prior beliefs to calculate posterior probabilities of increasedrelative risk (RR)) of VT/SCD with use of domperidone compared to non-use and ofharm, defined as risk exceeding 15%. The analyses were carried with normallydistributed priors (log (RR)): uninformative (N(0,10)) or informative (N(0.53,179)),derived from a meta-analysis (OR (95%CI):1.70 (1.47-1.97)). Sensitivity analyses used:different priors' strengths, different priors, and Bayesian meta-analysis RESULTS: The uninformative prior yielded a RR: 1.23 (95% credible interval (CrI):0.94-1.62), like the published frequentist RR: 1.22 (95% CI:0.99-1.50), with 69% probabilityof harm. With an informative prior weighted at 100%, 50% and 10%, the RR were 1.63(1.41-1.88), 1.57 (1.31-1.91) and 1.39 (1.10-1.93), respectively. The correspondingprobabilities of harm were 100%, 99%, and 94%, respectively.

Conclusion: While both the frequentist and Bayesian approaches with anuninformative prior were unable to reach a definitive conclusion concerning thearrhythmic risk of domperidone in PD patients, the Bayesian analysis with informativepriors showed a high probability of increased risk that was robust to multiple priorsensitivity analyses.

Keywords: Bayesian analysis; Domperidone safety; Observational study; Parkinson disease.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiparkinson Agents / adverse effects*
  • Antiparkinson Agents / therapeutic use
  • Bayes Theorem
  • Death, Sudden, Cardiac
  • Domperidone / adverse effects*
  • Domperidone / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy*
  • Risk Assessment
  • Tachycardia, Ventricular / chemically induced*

Substances

  • Antiparkinson Agents
  • Domperidone