June 09, 2015
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Anticoagulants safe for patients with brain metastases

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The use of anticoagulant medication did not increase the risk for intracranial hemorrhage among cancer patients with brain metastases, according to the results of a retrospective analysis.

Venous thromboembolism commonly occurs in cancer patients with brain metastases, according to study background. Despite the frequency of occurrence, the safety of anticoagulant medication in this patient population had not been adequately studied.

Jeffrey I. Zwicker, MD, assistant professor in the department of medicine of Beth Israel Deaconess Medical Center and Harvard Medical School, and colleagues conducted a control-matched cohort study using electronic health record data collected at Beth Israel Deaconess Medical Center between 1997 and 2014. Researchers identified 293 patients with cancer who had brain metastases, 104 of whom received enoxaparin for VTE. The other 189 patients served as controls.

Most patients in the cohort had non–small cell lung cancer (n = 153), followed by breast cancer (n = 37), renal cell carcinoma (n = 30), melanoma (n = 30), colorectal cancer (n = 14) and small cell lung cancer (n = 8).

The researchers conducted a blinded review of the available radiology reports, including head CT scans and brain MRI scans. They categorized intracranial hemorrhaging as trace (defined as < 1mL in volume), measurable (> 1 mL in volume), total (including both trace and measurable hemorrhage) and significant (> 10 mL in volume, symptomatic or requiring surgical intervention).

Researchers observed no difference in the cumulative incidence of intracranial hemorrhage at 1 year in the enoxaparin or control arms with regard to measurable (19% vs. 21%; HR = 1.02; 90% CI, 0.66-1.59), significant (21% vs. 22%) and total (44% vs. 37%) intracranial hemorrhage.

Researchers observed that the majority of significant intracranial hemorrhages in both arms were symptomatic (87.5% vs. 94.7%). Twenty-five percent of patients on the enoxaparin arm and 15.8% of the control arm required surgery for significant hemorrhages.

Patients with renal cell carcinoma or melanoma experienced a fourfold increased risk for intracranial hemorrhage compared with patients with NSCLC (HR = 3.98; 90% CI, 2.41-6.57). However, enoxaparin use did not significantly influence the increased risk.

Enoxaparin treatment significantly decreased the incidence of measurable intracranial hemorrhage (HR = 0.47; 90% CI, 0.27-0.8).

Researchers observed similar OS rates in the enoxaparin and control study arms (8.4 months vs. 9.7 months).

The researchers acknowledged several limitations of their study, including the inability to ascertain factors influencing the decision to administer anticoagulants in certain patients or identify independent risk factors used to determine anticoagulant safety.

Further, the researchers acknowledged their inability to reach their targeted number of patients for their analysis.

“While it is a very common clinical scenario to treat a patient with a metastatic brain tumor who also develops a blood clot, before this study there was very little data to inform the difficult decision of whether or not to anticoagulate these patients,” Zwicker said in a press release. “Our findings, which demonstrate that current practice is safe, should reassure physicians that anticoagulants can be safely administered to patients with brain metastases and a history of blood clots.” – by Cameron Kelsall

Disclosure: Zwicker reports research funding from Sanofi, consulting fees from Parexel and advisory roles with Merck and Portola Pharmaceuticals. The other researchers report no relevant financial disclosures.