Oral Anticoagulants Do Not Raise ARIA Risk of Anti-Amyloid Alzheimer Therapies, Study Shows

A systematic review and meta-analysis of randomized and non-randomized studies found no increased risk of amyloid-related imaging abnormalities (ARIA) among patients with Alzheimer disease (AD) receiving anti-amyloid monoclonal antibody therapies while on oral anticoagulants. The analysis addressed longstanding theoretical and empirical concerns that concomitant anticoagulant use could increase the frequency or severity of ARIA during anti-amyloid immunotherapy.¹

Published in the Journal of Neurology, Neurosurgery, & Psychiatry, the review included 5 eligible studies of anti-amyloid treatment for early AD that reported rates of ARIA or intracerebral hemorrhage (ICH) stratified by anticoagulant use. A total of 3837 participants were analyzed, including 1806 treated with lecanamab (Leqembi; Eisai) and 2031 treated with donanemab (Kisulna; Eli Lilly). Of note, non-human data and single-case reports were excluded from the analysis.

Overall, 286 participants received oral anticoagulants during anti-amyloid therapy (lecanemab, 156/1806; donanemab, 130/2031). All told, ARIA with edema or effusion (ARIA-E) occurred in 14% of patients, and ARIA with microhemorrhage or superficial siderosis (ARIA-H) present in 20% (lecanemab: 9% and 13%; donanemab: 21% and 28%) of treated patients. In addition, data from the meta-analysis demonstrated no significant difference in ARIA-E (14.3% vs 18.1%; pooled risk ratio [RR] 0.83, 95% CI, 0.63–1.11) or ARIA-H (20.0% vs 23.6%; RR, 0.86, 95% CI 0.68–1.09) between patients receiving anticoagulants and those who were not.

Overall, no significant subgroup differences were observed, and ARIA rates numerically favored anticoagulant use in patients treated with either lecanemab or donanemab. Furthermore, macrohemorrhages were rare, occurring in 4 anticoagulated patients (1.4%; all treated with lecanemab) and 8 non-anticoagulated patients (0.23%; five lecanemab, three donanemab).

“The meta-analysis outcomes of four clinical trials and a real-world study did not support the claim that oral anticoagulant use is associated with an increased risk of ARIA-E or ARIA-H in patients receiving anti-amyloid monoclonal antibody therapy,” noted first author Eckhard Schlemm, PhD, MBBS, neurologist in the Department of Neurology at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany, and study authors wrote.¹ “To more precisely define risks and benefits of anti-amyloid therapies in this subpopulation, our data support the inclusion of patients with AD receiving anticoagulants in carefully designed clinical trials, possibly exploring lower antibody doses, modified titration regimes, extended treatment intervals, and alternative strategies to remove amyloid.”¹

Current recommendations caution against combining oral anticoagulants with anti-amyloid monoclonal antibodies, and in the European Union (EU) and UK these therapies are not authorized for patients receiving anticoagulation. While the present analysis did not identify an increased ARIA risk, the low number of intracerebral hemorrhage (ICH) events, especially in patients treated with donanemab, limited the precision with which any excess ICH risk can be estimated.

Read More: NeurologyLive® Year in Review 2025: What Trials Could Reshape Alzheimer Care?

Safety considerations for AD therapies that target amyloid have been a concern since the class of medications first arrived. At the 2025 Alzheimer’s Association International Conference, held July 27-30, in Toronto, Canada, AD expert Sharon Cohen, MD, FRCPC, spoke with NeurologyLive^® to discuss the use of emerging AD therapies, focusing on lecanemab and donanemab.

In the interview, Cohen discussed the use of lecanemab and donanemab for early-stage AD and explained how each antibody targets different forms of amyloid and requires intravenous infusion at specific intervals. Cohen outlined eligibility criteria, including early symptomatic disease, confirmation of amyloid presence, and safety considerations such as pre-treatment MRI scans to assess ARIA risk. She also emphasized the importance of APOE genotyping to guide treatment decisions and the need to individualize therapy based on patient values.

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REFERENCES
1. Schlemm E, Gauthier S, Magnus T, et al. Risk of amyloid-related imaging abnormalities associated with anticoagulant therapy in patients with Alzheimer’s disease treated with anti-amyloid monoclonal antibodies: a systematic review and meta-analysis. Journal of Neurology, Neurosurgery & Psychiatry. December 2025; doi:10.1136/jnnp-2025-337386