Developing Topics.

Background: In CLARITY-AD, lecanemab both slowed cognitive decline and increased intracranial hemorrhages (ICHs), particularly among participants concurrently using anticoagulants. The Alzheimer's Association's expert guidance is to avoid co-prescribing; however, CMS and FDA do not restrict or warn against co-prescribing. We used a microsimulation model to quantify the potential benefits and harms of co-prescribing lecanemab and apixaban in people with atrial fibrillation (AF) experiencing mild cognitive impairment or early Alzheimer's.

Methods: We developed a microsimulation model to estimate the health and cognition-related quality of life among persons 65-90 years with AF and cognitive impairment. We compared four strategies over 18 months in a cohort of 100,000 people: apixaban alone, lecanemab and apixaban, lecanemab alone, and neither. We populated the cohort using the national Health and Retirement Study-AF cohort. Monthly model outcomes included ICH, ischemic stroke, cognitive impairment, quality-adjusted life months (QALMs), and survival. Increased ICH risk was a key input: a trial-reported 2.02-fold increase for lecanemab alone, a 2.21-fold increase for apixaban alone (anticoagulant literature), and a trial-reported 9.92-fold increase for lecanemab and anticoagulants together. We assigned quality-of-life estimates and mortality rates for people with cognitive impairment, stroke, and ICH. Background mortality rates increased with cognitive decline and following a stroke or ICH event.

Results: Over 18 months, apixaban alone would result in more QALMs (12.39 vs. 12.16), fewer ICH events (1,841 vs. 8,769), fewer deaths (17,652 vs. 21,199), but more cognitive decline (CDR-SB increase from baseline 1.42 vs. 1.01) compared to apixaban and lecanemab together (Table 2). In the 65 to 74-year-old age group, lecanemab and apixaban could be preferred (QALM 13.27 vs. 13.28) given the benefits of slowed cognitive decline but at the risk of 1,424 more ICH events/100,000 treated persons (Table 2). This finding is sensitive to the lecanemab-apixaban interaction on ICH risk (Figure).

Conclusion: These model-based results support apixaban alone as the preferred strategy for people with cognitive impairment and AF. Improved estimates of the lecanemab-anticoagulant interaction are critical to identifying the preferred strategy for people aged 65-74 years. These findings support the Alzheimer's Association's expert guidance to avoid co-prescribing lecanemab and anticoagulants.