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

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 useddifferent 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% CI0.99-1.50), 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.