Risk of serious ventricular arrhythmia and sudden cardiac death in a cohort of users of domperidone: a nested case-control study.
OBJECTIVE
Limited information from spontaneous reports and results of two case-control studies raised concern about the cardiotoxicity of oral domperidone therapy. This case-control study nested in a retrospective cohort evaluated the combined risk of serious ventricular arrhythmia (SVA) and sudden cardiac death (SCD) in users of domperidone compared with users of proton pump inhibitors (PPIs), or non-users of these medications.


METHODS
A cohort of users of domperidone or a PPI from 1990 to 2005 was identified from existing electronic databases of Saskatchewan Health. Possible cases of SVA/SCD were identified using hospital discharge and vital statistics codes. SVA cases were validated by cardiologist review of abstracted hospital medical charts. Up to four controls were matched to each case by index date, year of birth, sex, and diabetes status. The odds ratio (OR) of current domperidone exposure relative to non-use or to current PPI exposure was estimated and adjusted for possible confounding variables using conditional logistic regression.


RESULTS
From 83 212 individuals in the exposure cohort we identified 1608 cases, 49 SVA and 1559 SCD (mean age 79.4 years, females 52.9%, diabetes 22.3%) and 6428 matched controls. The adjusted OR for SVA/SCD with current domperidone use compared with non-use was (1.59, 95%CI: 1.28-1.98), or compared with current PPI use was (1.44, 95%CI: 1.12-1.86). In stratified analyses adjusted ORs were numerically higher in males, older subjects, and non-diabetics.


CONCLUSIONS
The increased risk of SVA/SCD for current domperidone users remained after adjustment for multiple covariates. The risk may vary among subgroups of exposed individuals.
Johannes
Catherine B
CB
Department of Pharmacoepidemiology and Drug Safety, RTI Health Solutions, 1440 Main Street, Suite 310, Waltham, MA 02451, USA. cjohannes@rti.org
Varas-Lorenzo
Cristina
C
McQuay
Lisa J
LJ
Midkiff
Kirk D
KD
Fife
Daniel
D
D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000453:epidemiology; D016022:Case-Control Studies; D016208:Databases, Factual; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D003920:Diabetes Mellitus / Q000453:epidemiology; D004294:Domperidone / Q000009:adverse effects*; D018492:Dopamine Antagonists / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D012525:Saskatchewan / Q000453:epidemiology; D012720:Severity of Illness Index; D012737:Sex Factors; D055815:Young Adult
D018492:Dopamine Antagonists; D054328:Proton Pump Inhibitors; D004294:Domperidone