Domperidone and Risk of Ventricular Arrhythmia and Cardiac Death: A Systematic Review and Meta-analysis
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Background and Objective
Domperidone is a drug used globally for relieving nausea and vomiting and stimulating breast milk production. Several case reports and studies linked domperidone usage with major cardiovascular adverse events (cardiac arrhythmia and sudden cardiac death). However, multiple randomized controlled efficacy studies failed to detect such adverse events. Our objectives were to systematically review and meta-analyze the association between current domperidone exposure and cardiovascular adverse events.
The first author performed EMBASE, PubMed and Scopus searches to identify human studies assessing the association between current domperidone exposure and cardiac arrhythmia or sudden death. Thirteen related articles were identified and the first and second authors independently reviewed the articles. Six studies were included in the final analysis. Meta-analysis was performed with a random effect model using the inverse variance approach. Heterogeneity was evaluated using the Q statistic and I 2 test.
Five case-control studies and one case-crossover study were included in this meta-analysis. Pooled risk estimates demonstrated that the current use of domperidone increased the risk of ventricular arrhythmia and sudden cardiac death (pooled adjusted odds ratio = 1.70; 95 % confidence interval 1.47–1.97; I 2 = 0 %). The I 2 test showed that the underlying population was homogeneous.
Evidence from this meta-analysis suggests that current domperidone use increases the risk of cardiac arrhythmia and sudden cardiac death by 70 %. Domperidone usage in older populations should be discouraged. Larger observational studies or randomized controlled trials are needed to confirm the findings of this analysis.
KeywordsCardiac Arrest Ventricular Arrhythmia Sudden Cardiac Death Metoclopramide Cisapride
Nattawut Leelakanok would like to acknowledge the support from The Royal Thai Government Scholarship. We thank Saket Girotra for his assistance. We also thank Xiaomei Gu for her help in developing search terms; Daniel Fife from Johnson & Johnson for his references list; Elizabeth Asztalos, Mathieu Pasquier, and Patrick Pun for providing useful information from their publications.
Compliance with Ethical Standards
There was no external source of funding. MLS receives salary support from a VA Health Services and Research Career Development Award (CDA 11-215).
Conflict of interest
NL, AH and MLS have no conflicts of interest to declare.
- 25.U.S. Department of Health and Human Services, U.S. Food and Drug Administration. FDA cautions breast-feeding moms. FDA Consum. 2004;38(5):6. Available at: http://permanent.access.gpo.gov/lps1609/www.fda.gov/fdac/departs/2004/504_upd.html#moms .
- 28.Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2014 [cited June, 2015 4]; Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
- 34.van Noord C, Dieleman JP, Verhamme K, Sturkenboom MC. Ventricular arrhythmia and sudden unexpected death and domperidone. Pharmacoepidememiol Drug Saf. 2009;18(S1):S155.Google Scholar
- 37.Arana A, Johannes C, Varas C, Rothman KJ, McQuay LJ, Yang Q, et al. Risk of out-of-hospital sudden cardiac death with use of domperidone, proton pump inhibitors, and metoclopramide. Pharmacoepidemiol Drug Saf. 2014;23:189.Google Scholar
- 38.Arana A, Johannes CB, McQuay LJ, Varas-Lorenzo C, Fife D, Rothman KJ. Risk of out-of-hospital sudden cardiac death in users of domperidone, proton pump inhibitors, or metoclopramide: a population-based nested case-control study. Drug Saf. 2015;38(12):1187–99.PubMedCentralCrossRefPubMedGoogle Scholar
- 40.Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. In: Higgins JPT GS, editor. The Cochrane Collaboration, 2011; 2011.Google Scholar
- 43.Manisty C, Hughes-Roberts Y, Kaddoura S. Cardiac manifestations and sequelae of gastrointestinal disorders. Br J Cardiol. 2009;16(4):6.Google Scholar