Abstract
BACKGROUND: Lecanemab slows cognitive decline among people with early Alzheimer's disease (early AD) but appears to increase the risk of intracranial hemorrhages (ICHs), including anticoagulant-related ICHs. OBJECTIVE: To examine the benefits and harms of co-prescribing lecanemab and anticoagulants in people with atrial fibrillation (AF) experiencing early AD. DESIGN: 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. DATA SOURCES: Clinical trials, observational cohorts. TARGET POPULATION: People 65-90 years with AF and early AD. TIME HORIZON: 18-month. INTERVENTION: Apixaban ( APIX ), apixaban and lecanemab ( APIX/LEC ), lecanemab ( LEC ), neither. OUTCOME MEASURES: ICH, ischemic stroke, cognitive decline, quality-adjusted life months (QALMs), and survival, age-stratified. RESULTS OF BASE CASE: For 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 ANALYSIS: Results are sensitive to lecanemab-anticoagulant interaction on ICH, baseline ICH risk, and lecanemab's effect on cognition. LIMITATIONS: Significant parameter uncertainty; treatment burden and costs were not modeled. CONCLUSIONS: Model-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 SOURCE: National Institute on Aging/National Institutes of Health (K76AG074919, P30AG062421, U01AG076478, and R01AG069575).