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

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 observational study were combined with prior beliefs to calculate posterior probabilities of increased relative risk (RR)) of VT/SCD with use of domperidone compared to non-use and of harm, defined as risk exceeding 15%. The analyses were carried with normally distributed 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% probability of 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 corresponding probabilities of harm were 100%, 99%, and 94%, respectively. Conclusion: While both the frequentist and Bayesian approaches with an uninformative prior were unable to reach a definitive conclusion concerning the arrhythmic risk of domperidone in PD patients, the Bayesian analysis with informative priors showed a high probability of increased risk that was robust to multiple prior sensitivity analyses. (c) 2021 Elsevier Inc. All rights reserved.