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.

Figure 1.

Among patients receiving oral anticoagulation pharmacotherapy from the VA with alcohol abuse, patient-level percent time in therapeutic range (TTR) vs. AST:ALT ratio, plotted using a cubic smoothing spline.