Safety of Direct Oral Anticoagulants in Central Nervous System Malignancies

Abstract

Patients with brain tumors are at high risk for thromboembolic complications and frequently require anticoagulation. Direct oral anticoagulants (DOACs) are a less burdensome treatment for cancer-associated thrombosis with safety and efficacy comparable to those of low molecular weight heparin (LMWH); however, there are few data to support the use of DOACs in patients with brain tumors. The purpose of this study was to better understand the safety profile of anticoagulants in patients with primary and metastatic brain tumors, with particular interest in the safety and efficacy of DOACs. Our hypothesis was that DOACs are as safe and effective as LWMH in this population. This study was conducted through a single-center retrospective chart review of 125 patients with primary and metastatic brain tumors on anticoagulation. Our primary outcomes were major bleeding and intracranial hemorrhage (ICH), with secondary outcomes of minor bleeding and recurrent thrombosis. The rate of major bleeding was 26% in the LMWH group versus 9.6% in the DOAC group (p = .03). The rate of ICH was 15% in the LMWH group versus 5.8% in the DOAC group (p = .09). The severity of ICH in both groups was low with median Common Terminology Criteria for Adverse Events version 5 scores of 2 in the LMWH group and 3 in the DOAC group. The rates of minor bleeding and recurrent thrombosis were low in both groups. Our conclusion is that DOAC use in patients with brain tumors is not associated with increased rates of major bleeding compared with LMWH and is a safe and effective option. IMPLICATIONS FOR PRACTICE: Patients with brain tumors are at high risk for venous thromboembolism and frequently require anticoagulation. Direct oral anticoagulants (DOACs) are less burdensome than low molecular weight heparin (LMWH) for treatment of thromboembolism, but there is concern in the community over increased risk of bleeding. This study provides much-needed objective evidence that there are fewer major bleeding events in patients with brain tumors on DOACs compared to LMWH with similar efficacy. As the paradigm of anticoagulation in patients with cancer shifts from LWMH toward DOACs, this work is particularly meaningful as it suggests DOACs are safe and effective for patients with brain tumors.

Keywords: Anticoagulation; Brain tumors; Intracranial hemorrhage; Thrombosis and hemostasis; Venous thromboembolism.

Figure 1

CTCAE scores in ICH events. Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events; DOAC, direct oral anticoagulant; ICH, intracranial hemorrhage; VTE, venous thromboembolism.