Anticoagulation in patients with brain cancer: an international registry

Patients with malignancy are at risk of developing cardiovascular complications which warrant anticoagulation, including venous thromboembolism (VTE) and atrial fibrillation (AF), with the former being especially prevalent in brain cancer. Anticoagulation in cancer patients is associated with an increased bleeding risk, particularly ICH. This increased risk of ICH with anticoagulation has been demonstrated in patients with high-grade glioma, but is yet to be confirmed in patients with metastatic brain cancer. There are scarce data on predictors of ICH in patients with brain cancer receiving anticoagulation. The PANWARDS score was not developed for cancer patients, but has been assessed in this setting with conflicting results.
Over the past decade and a half, low-molecular-weight heparin (LMWH) has been the standard anticoagulant in cancer patients with VTE, and accordingly most of the above data relates to LMWH treatment. Direct oral anticoagulants (DOACS) have recently become an alternative for treatment of cancer-associated thrombosis, but limited data exists regarding the safety of DOACs in patients with brain cancer. Two recent retrospective studies conducted by our groups have shown similar rates of ICH with LMWH and DOACs in patients with metastatic brain cancer. Rates of ICH in patients with primary brain tumors treated with DOACs (0 of 20 patients; 0%) were remarkably low, compared with LMWH (17 of 47 patients; 36.2%) in one of these cohorts, while the other demonstrated similar ICH rates, albeit with an even smaller sample. This data should be viewed as hypothesis-generating since the samples were small and confidence intervals were wide (e.g. HR 0.57; 95% CI 0.12-2.87 for major ICH with DOAC vs. LMWH in metastatic brain cancer). Although anticoagulation-related ICH is frequent in these patients, data on management (e.g. use of hemostatic/reversal agents and restarting anticoagulation) are scarce and outcomes appear to be poor. The lack of a definition for anticoagulation-associated ICH validated against clinical outcomes, hampers research in this field.
Accordingly, the following knowledge gaps remain: 1) ICH rate with DOACs in patients with brain cancer; 2) predictors of ICH in patients with brain cancer receiving anticoagulation; 3) Management and outcomes of anticoagulation-related ICH; 4) Validation and implementation of clinically relevant definitions of ICH.

DOACs are non-inferior to LMWH with regard to the risk of ICH in patients with brain cancer requiring anticoagulation.

Study index will be defined as the first day of concurrent anticoagulation and diagnosed brain cancer, and patients will be followed for 12 months.
Patients with anticoagulation-related ICH will be followed for an additional 90 days post ICH. Patients will be censored upon death, or migration/loss to follow-up and those discharged to receive terminal care will be considered deceased at the date of the last contact.

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