title: Alcohol misuse, genetics, and major bleeding among warfarin therapy patients in a community setting.
abstract: OBJECTIVE
  Little is known about the impact of alcohol consumption on warfarin safety, or whether demographic, clinical, or genetic factors modify risk of adverse events. We conducted a case-control study to assess the association between screening positive for moderate/severe alcohol misuse and the risk of major bleeding in a community sample of patients using warfarin.
  
  
  METHODS
  The study sample consisted of 570 adult patients continuously enrolled in Group Heath for at least 2 years and receiving warfarin. The main outcome was major bleeding validated through medical record review. Cases experienced major bleeding, and controls did not experience major bleeding. Exposures were Alcohol Use Disorders Identification Test Consumption Questionnaire (AUDIT-C) scores and report of heavy episodic drinking (≥5 drinks on an occasion). The odds of major bleeding were estimated with multivariate logistic regression models. The overall sample was 55% male, 94% Caucasian, and had a mean age of 70 years.
  
  
  RESULTS
  Among 265 cases and 305 controls, AUDIT-C scores indicative of moderate/severe alcohol misuse and heavy episodic drinking were associated with increased risk of major bleeding (OR = 2.10, 95% CI = 1.08-4.07; and OR = 2.36, 95% CI = 1.24-4.50, respectively). Stratified analyses demonstrated increased alcohol-related major bleeding risk in patients on warfarin for ≥1 year and in those with a low-dose genotype (CYP2C9*2/*3, VKORC1(1173G>A), CYP4F2*1), but not in other sub-groups evaluated.
  
  
  CONCLUSIONS
  Alcohol screening questionnaires, potentially coupled with genetic testing, could have clinical utility in selecting patients for warfarin therapy, as well as refining dosing and monitoring practices.
authors: Group Health Research Institute, Group Health, Seattle, WA, USA.|Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Joshua A
authors: JA
authors: Roth
authors: Group Health Research Institute, Group Health, Seattle, WA, USA.
authors: Katharine
authors: K
authors: Bradley
authors: Institute for Public Health Genetics, University of Washington, Seattle, WA, USA.|Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
authors: Kenneth E
authors: KE
authors: Thummel
authors: Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, WA, USA.|Institute for Public Health Genetics, University of Washington, Seattle, WA, USA.
authors: David L
authors: DL
authors: Veenstra
authors: Group Health Research Institute, Group Health, Seattle, WA, USA.|Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, WA, USA.
authors: Denise
authors: D
authors: Boudreau
mesh_terms: D000368:Aged; D000437:Alcoholism; D000925:Anticoagulants / Q000009:adverse effects*; D016022:Case-Control Studies; D003153:Community Health Services; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D006801:Humans; D007061:Idaho / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D011795:Surveys and Questionnaires; D014859:Warfarin / Q000009:adverse effects*; D014861:Washington / Q000453:epidemiology
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System
keywords: AUDIT-C; CYP2C9; CYP4F2; VKORC1; alcohol; major bleeding; pharmacoepidemiology; warfarin