Joshua A Roth1,2, Katharine Bradley1, Kenneth E Thummel3,4, David L Veenstra5,3, Denise Boudreau1,5. 1. Group Health Research Institute, Group Health, Seattle, WA, USA. 2. Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 3. Institute for Public Health Genetics, University of Washington, Seattle, WA, USA. 4. Department of Pharmaceutics, University of Washington, Seattle, WA, USA. 5. Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, WA, USA.
Abstract
PURPOSE: 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.
PURPOSE: 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: Nita A Limdi; T Mark Beasley; Michael R Crowley; Joyce A Goldstein; Mark J Rieder; David A Flockhart; Donna K Arnett; Ronald T Acton; Nianjun Liu Journal: Pharmacogenomics Date: 2008-10 Impact factor: 2.533
Authors: Stuart J Connolly; Michael D Ezekowitz; Salim Yusuf; John Eikelboom; Jonas Oldgren; Amit Parekh; Janice Pogue; Paul A Reilly; Ellison Themeles; Jeanne Varrone; Susan Wang; Marco Alings; Denis Xavier; Jun Zhu; Rafael Diaz; Basil S Lewis; Harald Darius; Hans-Christoph Diener; Campbell D Joyner; Lars Wallentin Journal: N Engl J Med Date: 2009-08-30 Impact factor: 91.245
Authors: Katharine A Bradley; Anna F DeBenedetti; Robert J Volk; Emily C Williams; Danielle Frank; Daniel R Kivlahan Journal: Alcohol Clin Exp Res Date: 2007-04-19 Impact factor: 3.455
Authors: Heather Liszka Rose; Peter M Miller; Lynne S Nemeth; Ruth G Jenkins; Paul J Nietert; Andrea M Wessell; Steven Ornstein Journal: Addiction Date: 2008-04-16 Impact factor: 6.526
Authors: N A Limdi; G McGwin; J A Goldstein; T M Beasley; D K Arnett; B K Adler; M F Baird; R T Acton Journal: Clin Pharmacol Ther Date: 2007-07-25 Impact factor: 6.875
Authors: Michael D Caldwell; Tarif Awad; Julie A Johnson; Brian F Gage; Mat Falkowski; Paul Gardina; Jason Hubbard; Yaron Turpaz; Taimour Y Langaee; Charles Eby; Cristi R King; Amy Brower; John R Schmelzer; Ingrid Glurich; Humberto J Vidaillet; Steven H Yale; Kai Qi Zhang; Richard L Berg; James K Burmester Journal: Blood Date: 2008-02-04 Impact factor: 22.113
Authors: Mohammed Zawiah; Al-Motassem Yousef; Amer Hayat Khan; Fahmi Y Al-Ashwal; Amal Matar; Batool ALKhawaldeh; Rand Nassar; Rami Abduljabbar; Abdullah Abdulmajid Abdo Ahmed Journal: PLoS One Date: 2020-06-17 Impact factor: 3.240
Authors: A Gundlund; Thomas Kümler; Anders Nissen Bonde; Jawad Haider Butt; Gunnar Hilmar Gislason; Christian Torp-Pedersen; Lars Køber; Jonas Bjerring Olesen; Emil Loldrup Fosbøl Journal: BMJ Open Date: 2019-09-20 Impact factor: 2.692