Retrospective Study of Bleeding Risk with Concomitant Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor and Anticoagulation.

Abstract

BACKGROUND\nPatients with cancer are at higher risk for venous thromboembolism (VTE) and bleeding, in turn complicating anticoagulant therapy. An added complexity is the toxicity profile of agents used to treat certain cancers, namely the vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF TKIs), which are associated with both thromboembolism and hemorrhages. The purpose of this study was to evaluate whether patients taking concurrent VEGF TKI and therapeutic anticoagulant were at higher risk for bleeding compared to patients taking VEGF TKI alone.\n\n\nMATERIALS AND METHODS\nThis was a single-center, retrospective chart review of patients who underwent treatment with a VEGF TKI with or without anticoagulant. The primary outcome included comparison of major bleeding rates between groups. Secondary outcomes included comparison of composite major and minor bleed rates and assessment of VTE incidence and recurrence among patients treated with a VEGF TKI and VEGF TKI plus anticoagulant, respectively.\n\n\nRESULTS\nA total of 184 and 74 patients were included in the VEGF TKI alone and VEGF TKI + anticoagulant groups, respectively. Major bleeding events occurred in 6/184 patients (3.3%) and 6/74 patients (8.1%), respectively (p=0.095). Composite major and minor bleeding events occurred in 22/184 (13.6%) and 17/74 (23%), respectively (p=0.026). 26/258 patients (10.1%) experienced a VTE event while taking a VEGF TKI, and 1/26 (3.8%) experienced a recurrent VTE event while taking a VEGF TKI plus anticoagulant.\n\n\nCONCLUSION\nPatients who received concomitant VEGF TKI plus anticoagulant had increased incidence of bleeding, though prospective studies are needed to further explore this association.\n\n\nIMPLICATIONS FOR PRACTICE\nThe current study showed that use of concomitant vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGF TKI) and therapeutic anticoagulation was associated with an increased risk of composite bleeding events, though at comparable rates between patients treated with VEGF TKI plus direct oral anticoagulant (DOAC) versus VEGF TKI plus non-DOAC anticoagulant. This suggests that when anticoagulation is indicated in a patient receiving a VEGF TKI, the novel DOACs may be a safe alternative to historical anticoagulants (warfarin and enoxaparin). These results fill a gap in the literature and will help guide treatment decisions for patients requiring concurrent VEGF TKI and anticoagulation.