Cancer patients with brain metastases who develop venous thromboembolism can safely receive anticoagulant therapy without increasing their risk for intracranial hemorrhage, according to new data.
Significant intracranial hemorrhage occurs in 20% to 50% of patients with metastatic brain tumors, report Jeffrey Zwicker, MD, from the Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, and colleagues. In their study of 293 patients with brain metastases, therapeutic anticoagulation with enoxaparin (Lovenox), a low-molecular-weight heparin, did not increase the risk for intracranial hemorrhage.
The study was published online May 18 in Blood.
"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," the authors write.
These findings "should reassure physicians that anticoagulants can be safely administered to patients with brain metastases and a history of blood clots," he said in a statement.
Common Complication
Venous thromboembolism is a common complication in patients with brain metastases, but even in the absence of anticoagulation, brain metastases are associated with high rates of spontaneous hemorrhage, the authors note.
However, published evidence regarding the safety of anticoagulation in this population is limited, and thus the decision to prescribe therapeutic anticoagulation can be challenging for physicians, they note. In addition, relatively few patients with brain metastasis have been enrolled in anticoagulant clinical trials; however, in patients without cancer, the case-fatality rate of intracranial hemorrhage in the setting of anticoagulation often exceeds 30%.
Dr. Zwicker and his colleagues evaluated patients with brain metastases to determine if the administration of therapeutic enoxaparin is associated with an increased risk for hemorrhage.
Of the 293 patients with confirmed brain metastases involved in the control-matched cohort study, 104 were assigned to enoxaparin therapy and 189 were assigned to the control group.
The predominant cancer subgroups in the study were non-small cell lung cancer, followed by breast cancer, renal cell carcinoma, and melanoma.
Aspirin use was significantly lower in the enoxaparin group than in the control group (4.8% vs 15.3%; P = .007). This is "presumably due to prescriber caution in administering dual antithrombotic therapy (aspirin and anticoagulant)," the authors report.
The enoxaparin regimen varied, with 76 patients (73.1%) receiving enoxaparin 1 mg/kg twice daily, 17 (16.3%) receiving 1.5 mg/kg once daily, and 11 (10.6%) with thrombocytopenia or renal failure receiving a reduced-dose modified regimen.
In 88 patients (84.6%), enoxaparin treatment was initiated after the diagnosis of brain metastases.
The rate of significant intracranial hemorrhage did not differ between the two groups.
At 1 year, the cumulative incidence of measurable intracranial hemorrhage was 19% in the enoxaparin group and 21% in the control group (hazard ratio [HR], 1.02; P = .97), and the majority of hemorrhages were symptomatic in both groups. In addition, the cumulative incidence of total intracranial hemorrhage was 44% in the enoxaparin group and 37% in the control group (P = .13).
For patients who experienced significant hemorrhage, neurosurgical intervention was required more often in the enoxaparin group than in the control group (25.0% vs 15.8%).
The risk for intracranial hemorrhage was four-fold higher in the 60 patients with melanoma or renal cell carcinoma than in the 153 with lung cancer (adjusted HR, 3.98; P < .001).
The administration of anticoagulants to patients with brain metastases is not consistent, in large part because there are very few data to confirm the safety of such agents, Dr. Zwicker told Medscape Medical News.
"There are clinicians who may recommend suboptimal therapy for the treatment of a thrombosis — such as placement of an inferior vena cava filter or subtherapeutic dosing of anticoagulation — in an attempt to minimize the risk of intracranial hemorrhage in this patient population," he explained.
The current findings, however, demonstrate that current practice is safe, Dr. Zwicker noted. "We did not observe an increased risk of intracranial hemorrhage in patients who received therapeutic enoxaparin, which does provide reassurance for a treating physician considering anticoagulation in a patient with brain mets."
But, he cautioned, "sound clinical judgment is necessary as enoxaparin was only used when considered appropriate by the treating physician."
This study received no pharmaceutical funding. Dr. Zwicker reports receiving previous research funding from Sanofi; serving on advisory committees for Portola Pharmaceuticals and Merck; and receiving consulting fees from Parexel.
Blood. Published online May 18, 2015. Abstract
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