Cancer and ischemic stroke
Understanding the connection between cancer and ischemic stroke requires current knowledge, future research.
The link between cancer and venous thrombosis is well known. The link between cancer and ischemic stroke, however, remains underappreciated and understudied.
Mary Cushman, MD, MSc, FAHA, university distinguished professor of medicine in the division of hematology and oncology at the University of Vermont Larner College of Medicine in Burlington, Vermont, said a key to treating cancer associated ischemic stroke is understanding its pathophysiology and how the two conditions are connected.
Cushman, who is director of the Thrombosis and Hemostasis Program at UVM Medical Center, is part of the panel for Wednesday’s session, “Cancer and Ischemic Stroke: An Underappreciated Etiology.”
Cushman pointed to the many unique factors and pathophysiologies that contribute to cancer-related stroke. These include:
- Hypercoagulability and thromboinflammation driven by the tumor or treatments
- Cancer therapy effects
- Nonbacterial thrombotic endocarditis
- Overt disseminated intravascular coagulation
- Tumor embolus
“These are important [to know] since they are unique to cancer patients from the point of view of their severity,” Cushman said. “Similar mechanisms might be related in noncancer patients, but the pathophysiology in that situation is more subtle.”
She said cancer-related stroke is an entity that has unique aspects compared to overall stroke. As such, prevention and treatment require different approaches.
“Cancer-related stroke is often triggered by the cancer itself or its treatments, which both can raise the risk of stroke through mechanisms not relevant in people without cancer,” she said. “For example, cancer cells produce procoagulants that enhance thrombogenicity and risk of stroke.”
To better understand the current research and treatment options, the American Heart Association and American Stroke Association recently issued a scientific statement, “Classification and Management of Ischemic Stroke in Patients With Active Cancer.” The paper comprehensively reviews the topic, proposes an etiologic classification paradigm for cancer-related ischemic stroke and acute and subsequent treatment approaches. Cushman and other panelists will discuss the statement and its implications during the session.
“This statement is really helpful as it brings together the literature on this topic into one place for readers to get a full appreciation of the research to date, which I hope will set the stage for stimulating future research in this area,” she said.
Session presenter Babak Navi, MD, MS, associate professor of neurology and neuroscience at Weill Cornell Medical College in New York City, said an area that needs additional study and research is secondary stroke prevention in patients with cancer-associated ischemic stroke.
“The risk of recurrent stroke in this population is approximately threefold that of ischemic stroke patients without cancer,” he said. “Further, patients with cancer-associated ischemic stroke also face an estimated 20% annual risk of major bleeding, so juggling the competing risks of recurrent stroke versus bleeding is challenging.”
Navi will discuss recent clinical trials and studies that have evaluated different forms of anticoagulant and antiplatelet therapy as forms of secondary prevention of ischemic stroke in patients with active cancer. These studies include:
- ENCHASE: a randomized trial comparing a direct oral anticoagulant versus low molecular weight heparin.
- TEACH: a pilot randomized trial comparing aspirin to low molecular weight heparin focused on feasibility
- ARCADIA and NAVIGATE ESUS: a pair of randomized trials that are the largest prospective analysis to date on the secondary prevention of ischemic stroke in cancer patients.
Navi, who is also vice chair for Neurology Hospital Services and division chief of stroke and hospital neurology at Weill Cornell Medical College, said these studies show that antiplatelet therapy, such as aspirin, may not be enough for patients with cancer-related stroke.
“Antiplatelets are the first line antithrombotic strategy for most ischemic strokes but perhaps may not be sufficiently strong for people with cancer-related stroke who have a tremendously high risk for recurrent stroke and other thromboembolic events,” he said.
Anticoagulant therapy, such as apixaban, are often viewed as more potent blood thinners than antiplatelet agents. Because of this, Navi said they are often used in strokes that are attributed to cardioembolism or clotting disorders, as well as in patients with both cancer and stroke. They are favored for stroke patients with cancer because of concerns over hypercoagulability, which occurs frequently in cancer patients. But Navi said the risks of the treatment may
not be worth it, and that more studies are needed.
“Any potential relative benefit that anticoagulants may provide over antiplatelet therapy could be offset by an increased risk of bleeding,” he said. “Therefore, randomized clinical trials comparing anticoagulant to antiplatelet therapy in patients with active cancer and ischemic stroke are needed to determine which is the optimal approach. None of these treatments are new. The real question is whether one provides net clinical benefit over the other for people with cancer-related stroke.”
Regardless of which treatment option is chosen, Navi said treating the underlying cancer and reducing cancer activity is probably the most effective strategy at preventing recurrent stroke in patients with cancer.
“Neurologists need to work closely with oncologists to start or resume cancer treatments when able. Otherwise, a self-fulfilling prophecy may develop,” he said.
