Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Jun;24(6):619-27.
doi: 10.1002/pds.3769. Epub 2015 Apr 8.

Alcohol misuse, genetics, and major bleeding among warfarin therapy patients in a community setting

Joshua A Roth  1   2 , Katharine Bradley  1 , Kenneth E Thummel  3   4 , David L Veenstra  5   3 , Denise Boudreau  1   5
Affiliations

Alcohol misuse, genetics, and major bleeding among warfarin therapy patients in a community setting

Joshua A Roth et al. Pharmacoepidemiol Drug Saf. 2015 Jun.

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.

Keywords: AUDIT-C; CYP2C9; CYP4F2; VKORC1; alcohol; major bleeding; pharmacoepidemiology; warfarin.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Odds of major bleeding associated with moderate/severe alcohol misuse among warfarin therapy patients
Figure 2
Figure 2
Odds of major bleeding associated with heavy episodic drinking among warfarin therapy patients
See this image and copyright information in PMC

References

    1. Kirley K, Qato DM, Kornfield R, Stafford RS, Alexander GC. National trends in oral anticoagulant use in the United States, 2007 to 2011. Circ Cardiovasc Qual Outcomes. 2012;5(5):615–621. - PMC - PubMed
    1. van Walraven C, Oake N, Wells PS, Forster AJ. Burden of potentially avoidable anticoagulant-associated hemorrhagic and thromboembolic events in the elderly. Chest. 2007;131(5):1508–1515. - PubMed
    1. Albers GW, Diener HC, Frison L, et al. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA. 2005;293(6):690–698. - PubMed
    1. Albers GW, Investigators S. Stroke prevention in atrial fibrillation: pooled analysis of SPORTIF III and V trials. Am J Manag Care. 2004;10(14 Suppl):S462–469. discussion S469-473. - PubMed
    1. Douketis JD, Arneklev K, Goldhaber SZ, Spandorfer J, Halperin F, Horrow J. Comparison of bleeding in patients with nonvalvular atrial fibrillation treated with ximelagatran or warfarin: assessment of incidence, case-fatality rate, time course and sites of bleeding, and risk factors for bleeding. Arch Intern Med. 2006;166(8):853–859. - PubMed

Publication types