Identifying the Risks of Anticoagulation in Patients with Substance Abuse
- 329 Downloads
Warfarin is effective in preventing thromboembolic events, but concerns exist regarding its use in patients with substance abuse.
Identify which patients with substance abuse who receive warfarin are at risk for poor outcomes.
Retrospective cohort study. Diagnostic codes, lab values, and other factors were examined to identify risk of adverse outcomes.
Veterans AffaiRs Study to Improve Anticoagulation (VARIA) database of 103,897 patients receiving warfarin across 100 sites.
Outcomes included percent time in therapeutic range (TTR), a measure of anticoagulation control, and major hemorrhagic events by ICD-9 codes.
Nonusers had a higher mean TTR (62 %) than those abusing alcohol (53 %), drugs (50 %), or both (44 %, p < 0.001). Among alcohol abusers, an increasing ratio of the serum hepatic transaminases aspartate aminotransferase/alanine aminotransferase (AST:ALT) correlated with inferior anticoagulation control; normal AST:ALT ≤ 1.5 predicted relatively modest decline in TTR (54 %, p < 0.001), while elevated ratios (AST:ALT 1.50–2.0 and > 2.0) predicted progressively poorer anticoagulation control (49 % and 44 %, p < 0.001 compared to nonusers). Age-adjusted hazard ratio for major hemorrhage was 1.93 in drug and 1.37 in alcohol abuse (p < 0.001 compared to nonusers), and remained significant after also controlling for anticoagulation control and other bleeding risk factors (1.69 p < 0.001 and 1.22 p = 0.003). Among alcohol abusers, elevated AST:ALT >2.0 corresponded to more than three times the hemorrhages (HR 3.02, p < 0.001 compared to nonusers), while a normal ratio AST:ALT ≤ 1.5 predicted a rate similar to nonusers (HR 1.19, p < 0.05).
Anticoagulation control is particularly poor in patients with substance abuse. Major hemorrhages are more common in both alcohol and drug users. Among alcohol abusers, the ratio of AST/ALT holds promise for identifying those at highest risk for adverse events.
KEY WORDSanticoagulation alcohol abuse drug abuse
No further contributors.
This study was supported by a grant from VA Health Services Research and Development (IIR-10-374). Dr. Rose is supported by a career development award from VA Health Services Research and Development (CDA-08-017). The sponsor had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, and approval of the manuscript.
The opinions expressed in this manuscript do not necessarily represent the official views of the Department of Veterans Affairs.
Dr. Rose is the guarantor of the entire manuscript.
No prior presentations.
Conflict of Interest
The authors declare that they do not have any conflicts of interest.
- 1.Compton WM, Thomas YF, Stinson FS, Grant BF. Prevalence, correlates, disability, and comorbidity of DSM-IV drug abuse and dependence in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry. 2007;64:566–76.PubMedCrossRefGoogle Scholar
- 2.Hasin DS, Stinson FS, Ogburn E, Grant BF. Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2007;64:830–42.PubMedCrossRefGoogle Scholar
- 6.Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 365:981–92.Google Scholar
- 10.Liangpunsakul S, Qi R, Crabb DW, Witzmann F. Relationship between alcohol drinking and aspartate aminotransferase:alanine aminotransferase (AST:ALT) ratio, mean corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), and apolipoprotein A1 and B in the U.S. population. J Stud Alcohol Drugs. 2010;71:249–52.PubMedGoogle Scholar
- 12.Bush K, Kivlahan DR, McDonell MB, Fihn SD, Bradley KA. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test. Arch Intern Med. 1998;158:1789–95.PubMedCrossRefGoogle Scholar
- 16.Jasuja GK, Reisman JI, Miller DR, et al. Identifying Major Hemorrhage with Automated Data: Results of the Veterans Affairs Study to Improve Anticoagulation (VARIA). Thrombosis research. 2012.Google Scholar
- 17.Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol. 2011;57:173–80.PubMedCrossRefGoogle Scholar
- 26.Connolly SJ, Pogue J, Eikelboom J, et al. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation. 2008;118:2029–37.PubMedCrossRefGoogle Scholar
- 28.Veeger NJ, Piersma-Wichers M, Tijssen JG, Hillege HL, van der Meer J. Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcome. A retrospective study of 2300 consecutive patients with venous thromboembolism. Br J Haematol. 2005;128:513–9.PubMedCrossRefGoogle Scholar
- 34.Hastie TJ, Tibshirani RJ. Generalized additive models. New York: Chapman and Hall; 1990.Google Scholar