title: Risk of serious ventricular arrhythmia and sudden cardiac death in a cohort of users of domperidone: a nested case-control study.
abstract: 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.
authors.affiliation: Department of Pharmacoepidemiology and Drug Safety, RTI Health Solutions, 1440 Main Street, Suite 310, Waltham, MA 02451, USA. cjohannes@rti.org
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Johannes
authors.forename: Cristina
authors.initials: C
authors.lastname: Varas-Lorenzo
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: McQuay
authors.forename: Kirk D
authors.initials: KD
authors.lastname: Midkiff
authors.forename: Daniel
authors.initials: D
authors.lastname: Fife
mesh_terms: 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
chemical_list: D018492:Dopamine Antagonists; D054328:Proton Pump Inhibitors; D004294:Domperidone