Lecanemab and Anticoagulants: Projected Effects on Health and Quality of Life

BackgroundLecanemab slows cognitive decline among people with early Alzheimers disease (early AD) but appears to increase the risk of intracranial hemorrhages (ICHs), including anticoagulant-related ICHs. ObjectiveTo examine the benefits and harms of co-prescribing lecanemab and anticoagulants in people with atrial fibrillation (AF) experiencing early AD. DesignMicrosimulation 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. Data SourcesClinical trials, observational cohorts Target PopulationPeople 65-90 years with AF and early AD Time Horizon18-month InterventionApixaban (APIX), apixaban and lecanemab (APIX/LEC), lecanemab (LEC), neither Outcome MeasuresICH, ischemic stroke, cognitive decline, quality-adjusted life months (QALMs), and survival, age-stratified. Results of Base CaseFor 100,000 simulated persons aged 65-74 years, APIX, APIX/LEC, and LEC would result in a similar clinical benefit (13.2 QALMs). Compared to APIX, APIX/LEC 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 [≥]75 years, APIX alone would always be preferred. Results of Sensitivity AnalysisResults are sensitive to lecanemab-anticoagulant interaction on ICH, baseline ICH risk, and lecanemabs effect on cognition. LimitationsSignificant parameter uncertainty; treatment burden and costs were not modeled. ConclusionsModel-based results support anticoagulants alone as the preferred strategy for people [≥]75 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. Primary Funding SourceNational Institute on Aging/National Institutes of Health (K76AG074919, P30AG062421, U01AG076478, and R01AG069575).