Study Analyzes Direct Oral Anticoagulants Use in Patients with Brain Metastases

Patients with brain metastases face a dual risk of both thrombosis and intracranial hemorrhage. Determining the optimal anticoagulation strategy for venous thromboembolism (VTE) in patients with brain metastases remains a significant clinical challenge. Now a real-world study by Cleveland Clinic researchers suggests that direct oral anticoagulants (DOACs) offer a safe alternative to low-molecular-weight heparin (LMWH) for these patients. The study findings were presented at the 2025 ASH annual meeting.

In the large, retrospective cohort study using the TriNetX database, 8,732 patients with brain metastasis and recent VTE treated with either a DOAC or LMWH between 2012 and 2023 were included. Disease-specific cohorts included lung cancer (N=5,138), breast cancer (N=1,528), colorectal cancer (N=780), melanoma (N=628) and renal cell carcinoma (N=658).

Researchers found that treatment with DOACs was associated with a significantly lower risk of intracranial hemorrhage (ICH) in patients with breast cancer or melanoma. There was a non-significant trend in lower bleeding rates in the other tumor types when treated with DOACs. In addition, there was significantly lower all-cause mortality and ICU admissions in patients with breast cancer, lung cancer or melanoma in those treated with DOAC.

Senior study author Dana Angelini, MD, a hematologist at Cleveland Clinic shared that the findings support guidelines that DOACs are an appropriate blood thinner to use in this population. “We still have to rely on individual risk assessment and shared decision-making with patients, but I think when faced with the two options, we can say that DOACs are at least as safe as low molecular weight heparin,” she says. They offer the patient an oral option that can be more convenient.”

Numerous trials over the past decade have supported the safety and efficacy of DOACs in treating thrombosis in patients with cancer. However, patients with brain tumors or metastases were not well represented in these studies or, in some cases, were excluded altogether. A few real-world studies have looked at the use of DOACs in these patients, but the studies published to date have been small.

There may be some clinical scenarios where LMWH remain a better choice, such as when patients are taking medications that interfere with DOACs, or when patients need frequent procedures that require anticoagulants to be paused. “Low-molecular heparin has the benefit of a shorter half-life over DOACs, so we often use injectables in those scenarios,” says Dr. Angelini.

While the study supports the safety of DOACs in this patient population, more research is needed, including prospective trials, as well as studies that look more closely at more specific subtypes of cancer and brain metastases. “More needs to be done, but I think this is helpful background that those types of studies could build on,” Dr. Angelini says.