Arana A, Johannes CB, Varas-Lorenzo C, Rothman KJ, McQuay LJ, Yang Q, Fife D. Risk of out-of-hospital sudden cardiac death with use of domperidone, prototon pump inhibitors, and metoclopramide. Poster presented at the 30th International Conference on Pharmacoepidemiology and Therapeutic Risk Management; October 2014. Taipei, Taiwan. [abstract] Pharmacoepidemiol Drug Saf. 2014 Oct; 23(S1):189.

BACKGROUND: Epidemiologic studies have linked exposure to domperidone (DOM) with serious cardiac arrhythmias, including sudden cardiac death (SCD), but most of these studies were small, and data relating risk to age, dose, and duration of use are limited.

OBJECTIVES: To clarify the risk of out-of-hospital SCD with use of DOM.

METHODS: We conducted a population-based case-control study nested (NCC) within a cohort drawn from theUK Clinical Practice Research Datalink (CPRD), linked to mortality and hospital data in 2005-2011. Controls were matched to SCD cases on age, sex, and practice. Risk of SCD in users of DOM relative to risk among users of proton pump inhibitors (PPI), metoclopramide (MET), and no use at the index date was evaluated with multivariable conditional logistic regression. We also conducted case-crossover (CC) analyses to address possible residual confounding by features of exposed subjects.

RESULTS: In the NCC analysis (3,397 SCD cases; 13,179 controls), the adjusted odds ratio (aOR) for SCD with current use of DOM alone (31 cases and 55 controls) compared with non-use of study medications (824 cases and 4,690 controls) was 2.09 (95% CI, 1.16-3.74); for oral MET, 4.29 (95% CI, 2.39-7.70); and for oral PPI, 1.32 (95% CI, 1.18-1.48). Compared with current MET use, the aOR for current DOM use was 0.42 (95% CI, 0.19-0.94) and compared with current PPI use was 1.58 (95% CI, 0.88-2.52). OR estimates were higher in the CC analysis than in the NCC analysis for DOM (3.33; 95% CI, 1.87-5.92) and for MET (4.78, 95% CI, 2.74- 8.36), but the OR for PPIs was near 1. There was a larger effect for current use of DOM alone compared with non-use among those aged > 60 years (aOR, 2.01; 95% CI, 1.12-3.62) than those aged 2-59 years, with a dose of > 30 mg/day (aOR, 4.52; 95% CI, 0.91-22.58) than lower doses, and with duration of use less tha 16 days, (aOR, 6.18; 95% CI, 2.48-15.4) than or equal to 16 days.

CONCLUSIONS: Susceptibility to SCD related to DOM exposure appears to be increased in certain subgroups of DOM users. The findings on MET were unexpected and should be evaluated in further studies.