A recent study co-authored by STATinMED Research1, evaluating the risk of major bleeding (MB), clinically relevant non-major (CRNM) bleeding, and recurrent venous thromboembolism (VTE) among VTE patients with active cancer, was featured as an oral presentation at the American Society of Hematology (ASH) 61st Annual Meeting and Exposition in Orlando, FL.

Cancer is an independent risk factor for VTE, and VTE risk is 4-7 times higher in cancer patients vs non-cancer patients. Cancers of the brain, pancreas, stomach, liver, lungs, and kidneys—and hematologic malignancies—have the strongest association with the occurrence of VTE. In patients with VTE and cancer, guidelines suggest using low molecular weight heparin (LMWH) over a vitamin K antagonist. However, the efficacy and safety of direct oral anticoagulants in comparison to LWMH has not been explored.

A pooled study using four US commercial insurance claims databases identified VTE patients diagnosed with active cancer (defined as cancer diagnosis or cancer treatment [chemotherapy, radiation, and cancer-related surgery] within 6 months before or 30 days after VTE diagnosis) who initiated apixaban, LMWH, or warfarin within 30 days following the first VTE event (01SEP2014-31MAR2018). Patients were followed to the earliest of health plan disenrollment, death, index therapy discontinuation, switch to another anticoagulant, study end, or a maximum of 6 months. Stabilized inverse probability treatment weighting (IPTW) was used to balance treatment cohorts. A subgroup analysis using the VTE risk scale was conducted. Patients were classified as high risk (lung, lymphoma, gynecologic, bladder, testicular, renal cell carcinoma), very high risk (stomach, brain, or pancreas), or other depending on their cancer type. Cox proportional hazard models were used to evaluate the risk of MB, CRNM bleeding, and recurrent VTE.

After matching, 3,393 apixaban, 6,108 LMWH, and 4,585 warfarin patients were identified with mean ages of 65, 64, and 64 years, respectively. After IPTW, all patient characteristics were balanced. After weighting, 40% of the patients had high risk cancer (lung, lymphoma, gynecologic, bladder, testicular, renal cell carcinoma) and 15% of the patients had very high risk cancer (brain, stomach, or pancreas). In the main analysis, apixaban patients had a lower risk of recurrent VTE and a similar risk of MB and CRNM bleeding compared to warfarin. Apixaban patients had a lower risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH. Warfarin patients had a similar risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH. The results in the VTE risk scale subgroup were generally consistent with the main analysis. There was a significant interaction for recurrent VTE among apixaban and warfarin patients compared to LMWH patients stratified by the VTE risk scale. Among patients in the very high risk and high risk cancer subgroups, apixaban and warfarin were associated with a similar risk of recurrent VTE compared to LMWH; among patients in the other cancer risk group, apixaban and warfarin patients had a lower risk of recurrent VTE compared to LMWH.

Adjusted risk of recurrent VTE

HR: hazard ratio; LMWH: low molecular weight heparin; VTE: venous thromboembolism

This study showed that VTE patients with active cancer initiating apixaban had a significantly lower risk of recurrent VTE compared to warfarin patients and a lower risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH patients. There was a difference in effect between apixaban and warfarin versus LMWH based on the VTE risk scale. Further trials are needed to evaluate the role of anticoagulants in the treatment of high risk cancer patients and to improve survival among VTE cancer patients.

Contact STATinMED today to see how our expert researchers and datasets can help with your next project.

1Cohen AT, Keshishian A, Lee T, Wygant G, Rosenblatt L, Hlavacek P, Mardekian J, Wiederkehr D, Sah J, Luo X. Safety and effectiveness of apixaban, LMWH and warfarin among venous thromboembolism (VTE) patients with active cancer: A subgroup analysis of VTE risk scale. 61st American Society of Hematology (ASH) Annual Meeting and Exposition. Orlando, FL: December 7-10, 2019. ORAL PRESENTATION.

Sign up to receive communications