{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:44:11Z","timestamp":1768567451994,"version":"3.49.0"},"posted":{"date-parts":[[2025,4,11]]},"group-title":"Geriatric Medicine","reference-count":63,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Lecanemab slows cognitive decline among people with early Alzheimer\u2019s disease (early AD) but appears to increase the risk of intracranial hemorrhages (ICHs), including anticoagulant-related ICHs.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To examine the benefits and harms of co-prescribing lecanemab and anticoagulants in people with atrial fibrillation (AF) experiencing early AD.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Microsimulation model to compare four treatment strategies. Using inputs from the literature, we modeled increased ICH risk with lecanemab (2.02-fold), apixaban (1.84-fold), and lecanemab\/apixaban interaction (2.67-fold). We assigned quality-of-life estimates and increased mortality risk with cognitive decline, stroke, and ICH.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Data Sources<\/jats:title>\n                  <jats:p>Clinical trials, observational cohorts<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Target Population<\/jats:title>\n                  <jats:p>People 65-90 years with AF and early AD<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Time Horizon<\/jats:title>\n                  <jats:p>18-month<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Intervention<\/jats:title>\n                  <jats:p>\n                    Apixaban (\n                    <jats:italic>APIX<\/jats:italic>\n                    ), apixaban and lecanemab (\n                    <jats:italic>APIX\/LEC<\/jats:italic>\n                    ), lecanemab (\n                    <jats:italic>LEC<\/jats:italic>\n                    ), neither\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Outcome Measures<\/jats:title>\n                  <jats:p>ICH, ischemic stroke, cognitive decline, quality-adjusted life months (QALMs), and survival, age-stratified.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results of Base Case<\/jats:title>\n                  <jats:p>\n                    For 100,000 simulated persons aged 65-74 years,\n                    <jats:italic>APIX<\/jats:italic>\n                    ,\n                    <jats:italic>APIX\/LEC<\/jats:italic>\n                    , and\n                    <jats:italic>LEC<\/jats:italic>\n                    would result in a similar clinical benefit (13.2 QALMs). Compared to\n                    <jats:italic>APIX<\/jats:italic>\n                    ,\n                    <jats:italic>APIX\/LEC<\/jats:italic>\n                    would result in more ICH events (1,990 vs. 400), all-cause deaths (5,820 vs. 5,140), but slower cognitive decline (mean CDR-SB change, 1.11 vs. 1.53). For persons \u226575 years,\n                    <jats:italic>APIX<\/jats:italic>\n                    alone would always be preferred.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results of Sensitivity Analysis<\/jats:title>\n                  <jats:p>Results are sensitive to lecanemab-anticoagulant interaction on ICH, baseline ICH risk, and lecanemab\u2019s effect on cognition.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Limitations<\/jats:title>\n                  <jats:p>Significant parameter uncertainty; treatment burden and costs were not modeled.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Model-based results support anticoagulants alone as the preferred strategy for people \u226575 years with early AD and AF. There was greater equipoise across treatment strategies for persons 65-74 years, for whom improved estimates of the ICH risk and lecanemab-anticoagulant interaction are critical to identifying the preferred strategy.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Primary Funding Source<\/jats:title>\n                  <jats:p>National Institute on Aging\/National Institutes of Health (K76AG074919, P30AG062421, U01AG076478, and R01AG069575).<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.04.03.25325187","type":"posted-content","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T11:15:11Z","timestamp":1744370111000},"source":"Crossref","is-referenced-by-count":0,"title":["Lecanemab and Anticoagulants: Projected Effects on Health and Quality of Life"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8400-6888","authenticated-orcid":false,"given":"Sachin J.","family":"Shah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tai","family":"Dinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Blacker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven M.","family":"Greenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Giardina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacquelyn M.","family":"Lykken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samhita","family":"Kalidindi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia","family":"Qoshe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph P.","family":"Newhouse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ankur","family":"Pandya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily P.","family":"Hyle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025041500550914000_2025.04.03.25325187v1.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJ-Moa2212948"},{"issue":"3","key":"2025041500550914000_2025.04.03.25325187v1.2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1001\/jamaneurol.2021.5205","article-title":"Amyloid-Related Imaging Abnormalities and \u03b2-Amyloid\u2013Targeting Antibodies: A Systematic Review","volume":"79","year":"2022","journal-title":"JAMA Neurol"},{"issue":"1","key":"2025041500550914000_2025.04.03.25325187v1.3","first-page":"354","article-title":"Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer\u2019s disease clinical trials","volume":"5","year":"2019","journal-title":"Alzheimer\u2019s & Dementia: Translational Research & Clinical Interventions"},{"issue":"2","key":"2025041500550914000_2025.04.03.25325187v1.4","doi-asserted-by":"crossref","first-page":"e12388","DOI":"10.1002\/trc2.12388","article-title":"Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer\u2019s disease clinical trials","volume":"9","year":"2023","journal-title":"Alzheimers Dement (N Y)"},{"issue":"5","key":"2025041500550914000_2025.04.03.25325187v1.5","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1002\/alz.13770","article-title":"Minimal clinically important difference in Alzheimer\u2019s disease: Rapid review","volume":"20","year":"2024","journal-title":"Alzheimer\u2019s & Dementia"},{"issue":"10367","key":"2025041500550914000_2025.04.03.25325187v1.6","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1016\/S0140-6736(22)02480-1","article-title":"Lecanemab for Alzheimer\u2019s disease: tempering hype and hope","volume":"400","author":"The Lancet","year":"2022","journal-title":"The Lancet"},{"issue":"11","key":"2025041500550914000_2025.04.03.25325187v1.7","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/S2215-0366(21)00197-8","article-title":"The need to show minimum clinically important differences in Alzheimer\u2019s disease trials","volume":"8","year":"2021","journal-title":"The Lancet Psychiatry"},{"key":"2025041500550914000_2025.04.03.25325187v1.8","doi-asserted-by":"crossref","unstructured":"Sabbagh M. 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