Supplementary Material for: Comparative Safety and Effectiveness of Direct Oral Anticoagulants and Warfarin during Chemotherapy in Cancer Patients with Venous Thromboembolism Aged 75 Years or Older：A Nationwide Inpatient Database Study

Introduction Venous thromboembolism (VTE) is a life-threatening complication occurring in cancer patients. Direct oral anticoagulants (DOACs) or warfarin are widely prescribed for treating cancer-associated VTE. However, data are sparse as to the effectiveness and bleeding complications associated with these medications in elderly patients. The purpose of this study was to compare effectiveness and safety profiles between DOACs and warfarin in elderly cancer patients undergoing chemotherapy. Methods Using the Diagnosis Procedure Combination inpatient database, we retrospectively identified cancer patients aged ≥75 years who developed VTE during chemotherapy (n=4,278, January 2016 to March 2020). Eligible patients were divided into those receiving warfarin (n=557) and DOACs (n=3,721). We conducted a 1:4 propensity score matching analysis to adjust for measured confounders. The primary outcome was VTE recurrence requiring hospitalization. Secondary outcomes were major bleeding requiring hospitalization and in-hospital death from all causes within six months. Results The propensity-matched cohort included 557 patients in the warfarin group and 2,278 patients in the DOACs group. The proportion of VTE recurrence requiring hospitalization was lower in the DOACs group (5.3% vs. 7.5%; odds ratio [OR], 0.69; 95% confidence 50 interval [CI], 0.48–0.98). The proportion of recurrent deep vein thrombosis was 6.3% and 4.4%, while that of recurrent pulmonary emboli was 1.3% and 1.3% in the warfarin and DOACs groups, respectively. No statistically significant differences were found in the proportion of major bleeding events requiring hospitalization (1.6% vs. 1.1%; OR, 1.47; 95% CI, 0.62–3.50) or all-cause in-hospital mortality(11.1% vs. 9.9%; OR, 1.14; 95% CI, 0.84–1.56) between the two groups. Discussion/Conclusion Our findings suggest that DOACs may be more effective than warfarin in terms of VTE recurrence requiring hospitalization, and that these medications may be equivalent in terms of safety.