Survival outcomes with warfarin compared with direct oral anticoagulants in cancer-associated venous thromboembolism in the United States: A population-based cohort study

Background
Direct oral anticoagulants (DOACs) have comparable efficacy with low-molecular-weight heparin (LMWH) for the treatment of cancer-associated venous thromboembolism (VTE). Whether there is a mortality benefit of DOACs compared with warfarin in the management of VTE in cancer is not established.

Methods and findings
Utilizing the United States’ Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases from 2012 through 2016, we analyzed overall survival in individuals diagnosed with a primary gastric, colorectal, pancreas, lung, ovarian, or brain cancer and VTE who received a prescription of DOAC or warfarin within 30 days of VTE diagnosis. Patients were matched 1:2 (DOAC to warfarin) through exact matching for cancer stage and propensity score matching for age, cancer site, cancer stage, and time interval from cancer to VTE diagnosis. The analysis identified 4,274 patients who received a DOAC or warfarin for the treatment of VTE within 30 days of cancer diagnosis (1,348 in DOAC group and 2,926 in warfarin group). Patients were of median age 75 years and 56% female. Within the DOAC group, 1,188 (88%) received rivaroxaban, and 160 (12%) received apixaban. With a median follow-up of 41 months, warfarin was associated with a statistically significantly higher overall survival compared to DOACs (median overall survival 12.0 months [95% confidence interval (CI): 10.9 to 13.5] versus 9.9 months [95% CI: 8.4 to 11.2]; hazard ratio (HR) 0.85; 95% CI: 0.78 to 0.91; p < 0.001). Observed differences in survival were consistent across subgroups of cancer sites, cancer stages, and type of VTE. The study limitations include retrospective design with potential for unaccounted confounders along with issues of generalizability beyond the cancer diagnoses studied.

Conclusions
In this analysis of a population-based registry, warfarin was associated with prolonged overall survival compared to DOACs for treatment of cancer-associated VTE.