Effectiveness and safety of apixaban, low-molecular weight heparin, and warfarin among high-risk subgroups of venous thromboembolism patients with active cancer
Authors: Cohen A , Keshishian A , Lee T , Wygant G , Rosenblatt L , Hlavacek P , Sah J , Luo X 
Published: November 2020

Abstract

Background
Cancer-associated venous thromboembolism (VTE) carries a high risk for recurrent events and major bleeding (MB) which further increases among some high-risk subgroups of patients.

Purpose
This study evaluates recurrent VTE and MB among VTE patients with active cancer within 6 months of initiating apixaban, low-molecular weight heparin (LMWH), or warfarin stratified by cancer type, cancer treatment, and VTE characteristics.

Methods
Four US commercial insurance claims databases were pooled to identify VTE patients with active cancer (defined as ≥1 claim with cancer diagnosis [any stage] or cancer treatment [chemotherapy, radiation, and cancer-related surgery] within 6 months before to 30 days after VTE diagnosis). Patients who initiated apixaban, LMWH, or warfarin within 30 days following the first VTE event (01SEP2014–31MAR2018) were included. Treatment cohorts were balanced using stabilized inverse probability treatment weighting (IPTW). Cox proportional hazards models were used to estimate hazard ratios of recurrent VTE and MB for each subgroup stratification: metastatic diagnosis, cancer treatment, chemotherapy, upper and lower gastrointestinal (GI) cancer, and VTE event type (PE with or without deep vein thrombosis [DVT] versus DVT only). Statistical significance (P&lt;0.10) of the interaction between the subgroup strata and outcomes were evaluated.

Results
A total of 3,393 apixaban, 6,108 LMWH, and 4,585 warfarin patients were identified with a mean follow-up of 105–166 days across cohorts. After IPTW, all patient characteristics were balanced. In the overall population, apixaban had a lower risk of recurrent VTE and MB vs. LMWH. Warfarin had a similar risk of recurrent VTE and MB vs. LMWH. Apixaban had a lower risk of recurrent VTE and a similar risk of MB vs. warfarin (Figure). Analyses stratified by metastatic diagnosis, cancer treatment, chemotherapy, VTE event type, and GI cancer show generally consistent results across the subgroups (most of the p values for interaction &gt;0.10) and with the overall population. There was a significant interaction in cancer treatment strata: apixaban trended towards a lower risk of MB vs. LMWH with or without cancer treatment; however, patients without cancer treatment had a larger difference vs. patients with cancer treatment. Two significant interactions were observed in metastatic diagnosis strata: apixaban and warfarin had a lower risk of recurrent VTE vs. LMWH in patients without a metastatic diagnosis whereas apixaban and warfarin had similar risk of recurrent VTE vs. LMWH in patients with a metastatic diagnosis (Figure).

Conclusion
Across these high-risk subgroups of VTE cancer patients, apixaban generally had a lower risk of recurrent VTE and MB vs. LMWH and lower risk of recurrent VTE compared to warfarin. Warfarin patients generally had a similar risk of recurrent VTE and MB vs. LMWH. The findings are generally consistent with the overall population results.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Pfizer Inc. and Britstol-Myers Squibb Company.