Identifying the Risks of Anticoagulation in Patients with Substance Abuse

Abstract

BACKGROUND: Warfarin is effective in preventing thromboembolic events, but concerns exist regarding its use in patients with substance abuse. OBJECTIVE: Identify which patients with substance abuse who receive warfarin are at risk for poor outcomes. DESIGN: Retrospective cohort study. Diagnostic codes, lab values, and other factors were examined to identify risk of adverse outcomes. PATIENTS: Veterans AffaiRs Study to Improve Anticoagulation (VARIA) database of 103,897 patients receiving warfarin across 100 sites. MAIN MEASURES: Outcomes included percent time in therapeutic range (TTR), a measure of anticoagulation control, and major hemorrhagic events by ICD-9 codes. RESULTS: 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).CONCLUSIONS: 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.

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

“…This is the first study to our knowledge to evaluate the association between common alcohol screening instruments and major bleeding risk in a community sample of warfarin patients. A single previous study of veteran patients on warfarin assessed whether screening positive for any (mild) alcohol misuse on AUDIT‐C (≥3 points women or 4 points men) was associated with anticoagulation control or bleeding and found no association . Our findings for the association between screening positive for moderate/severe alcohol misuse and major bleeding are consistent with a variety of established behavioral and biologic effects.…”

“…We calculated AUDIT‐C scores in the typical manner with each question scored 0–4 points, with total AUDIT‐C scores (0–12 points) being the sum of the individual items. We evaluated moderate/severe alcohol misuse (AUDIT‐C scores of 5–7 and 8–12, respectively), because scores of 5–12 are associated with upper gastrointestinal bleeding and other complications, and AUDIT‐C scores ≤4 can be obtained by drinking within AHA guidelines and are not associated with poor warfarin outcomes . Because of the limited number of patients who screened positive for severe misuse ( n = 12), we analyzed a dichotomous AUDIT‐C measure of alcohol misuse (no/mild or moderate/severe).…”

“…Among the many risk factors for major bleeding on warfarin, alcohol use is among the strongest but least well studied in practice . For example, the American Heart Association (AHA) cautions patients taking warfarin to use alcohol infrequently and limit to one to two drinks, but specific evidence is not cited .…”

Population attributable fractions of risk factors for hepatocellular carcinoma in the United States

“…24, 27 To identify risk factors, International Classification of Diseases, version 9 (ICD-9) codes were used to capture medical conditions and key health risk behaviors (Table 1). Because obesity, diabetes, impaired glucose metabolism (IGM), metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) are highly correlated disorders, these conditions were combined into one group, referred to as ‘metabolic disorders.’ Rare genetic disorders (porphyrias, hemochromatosis, Wilson, alpha-1 antitrypsin deficiency and glycogen storage diseases) known to be associated with HCC were combined into a single group, referred to as ‘genetic disorders.’ Because the SEER-Medicare database contains limited information on alcohol consumption, a collection of alcohol-related medical conditions in addition to reported history of alcohol abuse were used as the proxy variable for heavy alcohol consumption under the variable heading ‘alcohol.’ 28 Similarly, the combination of chronic obstructive pulmonary disease (COPD) 29 and tobacco use were used as a proxy for heavy smoking under the variable heading ‘smoking’. Thus, the following factors were analyzed for odds ratios (ORs) and PAFs: metabolic disorders, HCV, HBV, genetic disorders, alcohol, and tobacco.…”

Capsule Commentary on Efird et al., Identifying the Risks of Anticoagulation in Patients with Substance Abuse

“…Efird et al analyzed the US Department of Veterans Affairs (VA) database to retrospectively assess the risk of anticoagulation among substance abusers. 4 They determined that both alcohol and drug abusers had significantly worse anticoagulation control, and higher rates of bleeding independent of anticoagulation control. Poor outcomes were substantially higher for drug abusers than alcohol abusers.…”