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.

Low dose apixaban as secondary prophylaxis of venous thromboembolism in cancer patients – 30 months follow‐up

“…In our study, metastatic brain bleed only occurred in patients without verified cerebral metastases at inclusion. Several retrospective studies indicate a comparable safety profile between oral factor Xa inhibitors and LMWHs in patients with cerebral metastases and primary cerebral tumors 27–29 . The current data illustrates that the actual rate of patients with cerebral metastases is uncertain if you do not do cerebral CT‐scan at inclusion.…”

Treatment Algorithm in Cancer-Associated Thrombosis: Updated Canadian Expert Consensus

“…When anticoagulation was analyzed as a time-varying covariate, the risk of any ICH did not differ between DOAC- and LMWH-treated patients (HR: 0.98; 95% CI 0.28 to 3.40) [ 46 ]. Finally, a single-center retrospective chart review of 125 patients with primary and metastatic brain tumors on anticoagulation reported rates of major bleeding of 26% and 9.6% in patients receiving LMWH or DOAC, respectively [ 47 ]. Patients receiving DOAC also had a lower rate of ICH compared to those receiving LMWH (5.8% vs. 15%) [ 47 ].…”

“…Finally, a single-center retrospective chart review of 125 patients with primary and metastatic brain tumors on anticoagulation reported rates of major bleeding of 26% and 9.6% in patients receiving LMWH or DOAC, respectively [ 47 ]. Patients receiving DOAC also had a lower rate of ICH compared to those receiving LMWH (5.8% vs. 15%) [ 47 ]. Nevertheless, given the small numbers and the limitations of retrospective studies, as well the shorter half-life of LMWH, the consensus committee suggests considering the initial use of LMWH for patients with CAT and high-risk intracranial lesions (e.g., glioma).…”

2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19

“… 79 In the second chart review study (n=125), the rate of major bleeding was 9·6% under direct oral anticoagulants versus 26% under LMWHs (p=0·03), and the respective rates of intracerebral haemorrhage were 5·8% and 15% (p=0·09), with no difference in minor bleeding and recurrent VTE. 80 In the third study (n=111), the 6-month cumulative incidence of intracerebral haemorrhage was 4·3% (95% CI 0·74–13·2) with direct oral anticoagulants versus 5·9% (1·5–14·9) with LMWHs, and the 6-month cumulative incidence of bleeding was 14·3% (6·2–25·8) versus 27·8% (15·5–41·6), respectively. 81 Rates of recurrent VTE did not differ between groups.…”