Survival assessment of warfarin and international normalized ratio exposure in cancer-associated venous thromboembolism: Veterans Affairs healthcare system-based analysis

Abstract

Venous thromboembolism (VTE) is a common complication among patients with cancer. While randomized clinical trials have established the safety and efficacy of direct oral anticoagulants (DOACs) and low-molecular-weight heparin (LMWH) relative to warfarin for the treatment of cancer-associated thrombosis, emerging evidence suggests that warfarin may be associated with improved overall survival in patients with malignancy. To evaluate survival outcomes among patients with cancer and VTE treated with warfarin compared with other anticoagulants within the Veterans Affairs (VA) Health Care System and analyze the association of international normalized ratio (INR) exposure and overall survival. Among 12 298 propensity-matched patients (mean age 69 years; 97% men), warfarin use was associated with a 16% lower risk of mortality compared with other anticoagulants (hazard ratio [HR], 0.84; (95% CI, 0.80-0.88); P < .001). Median survival was 1457 days in the warfarin group vs 1045 days in the non–warfarin group. Survival benefits were consistent across subgroups defined by tumor type, stage, and demographic characteristics. In landmark analyses the greatest benefit was observed with extended periods in the INR range of 2.5 to 3.0 (HR, 0.81; 95% CI, 0.75-0.87). In this population-based cohort study of patients with cancer and VTE, warfarin use was associated with improved survival compared with other anticoagulants. The greatest benefit was observed among patients who maintained an INR between 2.5 and 3.0.