Clinical data have demonstrated prolongation of the QTc interval associated with domperidone use. The risk of serious ventricular arrhythmias (SVA) in clinical practice in China has not been investigated.
The incidence of SVA and all-cause cardiac arrest associated with medications for gastrointestinal disorders in China was assessed in a retrospective cohort study using information from electronic medical record databases from the Xijing and Guangzhou general hospitals. Inpatients and outpatients with at least one prescription for domperidone, mosapride/itopride, metoclopramide, a proton pump inhibitor (PPI), or histamine H2 receptor antagonist were identified in the hospital databases from January 1, 2009 to December 31, 2014.
The inpatient exposure cohorts included 66,282 inpatients at Xijing and 23,643 inpatients at Guangzhou hospitals. There were 67 cases of SVA and two cases of SVA at the respective hospitals during the study period. Three cases (all at Xijing) occurred in patients prescribed domperidone (incidence rate 2.9/100 person-years (PYs), 95% CI 0.9–9.0) compared to 1.3/100 PYs (95% CI 0.2–8.9) for mosapride/itopride and 5.6/100 PYs (95% CI 4.4–7.2) for PPIs. The hazard ratio adjusted for age, sex, and co-morbidities for SVA in patients prescribed domperidone compared to PPIs was 0.79 (95% CI 0.25–2.56). There were 44 cases of all-cause cardiac arrest at Xijing and 21 at Guangzhou hospital. Three patients had received domperidone and all had underlying cardiovascular diseases.
SVA and cardiac arrest are very rare events in patients prescribed medications for gastrointestinal disorders in China. We found no evidence that domperidone carried a higher risk of SVA compared to other gastrointestinal medications.
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Sponsorship for this study and the journal’s Rapid Service Fee were funded by Janssen Research & Development LLC.
Medical Writing and Editorial Assistance
Medical writing and editorial support were provided by Joanne Wolter and Gayle Murry, which was funded by Janssen Research & Development LLC.
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
As principal investigator, Kaichun Wu supervised this study and took responsibility for the integrity and accuracy of the data. Yongjing Zhang, Hong Qiu, and Kaichun Wu developed the study concept and design. Meng Shu, Wenhua Liang, and Kun Jiang led the data transformation, validation, and statistical analysis. Dianxin Zhang and Wenhua Liang contributed to key definition constructions from clinical knowledge and practice perspective. All authors provided input on the interpretation of data and critically revised the manuscript for important intellectual content. The authors would like to thank DF (Janssen Research & Development LLC, US) for scientific consultancy, QL, PW, and SH Chong (Xian Janssen Pharmaceutical Ltd., China) for clinical and regulatory policy consultancy.
Dr. Yongjing Zhang, Meng Shu, and Dr. Hong Qiu are employees of Janssen Research & Development, LLC and Dr. Yongjing Zhang and Dr. Hong Qiu hold stock in Johnson & Johnson Pte, Ltd. Prof. Kaichun Wu, Prof. Dianxin Zhang, Prof. Kun Jiang, and Prof. Wenhua Liang have nothing to disclose.
Compliance with Ethics Guidelines
Patient consent was not required for the retrospective use of de-identified, electronic data. The study protocol was approved by Institutional Review Boards in both Xijing Hospital, the Fourth Military Medical University and the First Affiliated Hospital of Guangzhou Medical University. The ethics approval was waived by the Human Ethics Committees in both study hospitals, because this retrospective observational study could not track any individual patient, nor have any impact on the clinical treatments.
The datasets generated during and/or analyzed during the current study are not publicly available due to the regulatory restrictions of Xijing Hospital, the Fourth Military Medical University and the First Affiliated Hospital of Guangzhou Medical University but are available from the corresponding author on reasonable request.
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Zhang, Y., Shu, M., Liang, W. et al. Risk of Serious Ventricular Arrhythmia in Users of Gastrointestinal Medications: A Retrospective Cohort Study in China. Adv Ther 37, 1564–1578 (2020). https://doi.org/10.1007/s12325-020-01271-8
- Sudden death
- Ventricular arrhythmia