Class of Alzheimer's drug presents unique challenge for patients with cardiovascular disease

A new Viewpoint article published in the Journal of the American Medical Association (JAMA), titled " Use of Lecanemab for Patients with Cardiovascular Disease—The Challenge of Uncertainty," advocates for additional research to improve decision making prior to initiating lecanemab, commercially known as Leqembi, an FDA-approved Alzheimer's Disease drug.

According to Darae Ko, MD, MSc, a cardiologist and researcher at Hebrew SeniorLife's Hinda and Arthur Marcus Institute for Aging Research, and others, advanced care planning prior to initiation of lecanemab and other anti-amyloid monoclonal antibodies (mAbs) approved in the future is important so that clinicians, patients, and their families are fully aware of the unknowns, especially for patients with cardiovascular disease that may require anticoagulants or thrombolytics.

The authors note that while "in the initial phase of the drug rollout, patients are being carefully selected to minimize the potential side effects of the drug (but) a major safety concern … has been amyloid-related imaging abnormalities (ARIA), the most concerning of which is cerebral microhemorrhages. The risk was higher in patients on anticoagulation," said Dr. Ko.

Antithrombotic therapy presents a unique challenge for patients considering some Alzheimer's drugs. In their Viewpoint, the authors note that in approving lecanemab, the FDA did not advise regarding the risk of concurrent anticoagulation therapy and that "the Alzheimer's Association's Therapeutics Work Group took a more conservative approach and recommended that persons with cerebral amyloid angiopathy and those currently prescribed anticoagulants should not be candidates for lecanemab because the risk of bleeding outweighs the potential benefit."

"We anticipate that three common acute clinical conditions—ischemic stroke, myocardial infarction, and pulmonary embolism—for which treatment with thrombolytics and anticoagulation are critical and clinical decisions must be made emergently, will be particularly challenging in patients treated with anti-amyloid mAb and will require careful advance directive conversations with patients," they wrote in the paper.

Decisions regarding the use of lecanemab, an important advance in the treatment of Alzheimer's, are currently based on limited safety data. "To meet this challenge," the authors note, "there is a pressing need to create multidisciplinary treatment teams for Alzheimer's Disease, develop shared decision-making models for advanced care planning, and produce the empiric data needed to guide treatment decisions."