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Lecanemab and Anticoagulants: Projected Effects on Health and Quality of Life
Insights
Lecanemab slows Alzheimer's decline but increases bleeding risk. For patients 75+, anticoagulants alone are preferred. For younger patients, the optimal strategy requires more data on lecanemab-anticoagulant interactions.
Area of Science:
- Neurology
- Geriatrics
- Pharmacology
Background:
- Lecanemab shows promise in slowing early Alzheimer's disease (AD) cognitive decline.
- However, it is associated with an increased risk of intracranial hemorrhages (ICHs), particularly when combined with anticoagulants.
Purpose of the Study:
- To evaluate the benefits and risks of co-prescribing lecanemab with anticoagulants (specifically apixaban) in patients with atrial fibrillation (AF) and early AD.
Main Methods:
- A microsimulation model was used to compare four treatment strategies: apixaban alone, lecanemab alone, co-prescription, and neither.
- The model incorporated literature-based estimates of ICH risk for lecanemab, apixaban, and their interaction, alongside quality-of-life and mortality data.
Main Results:
- For individuals aged 65-74 with AF and early AD, co-prescription (apixaban/lecanemab) resulted in similar clinical benefit (QALMs) but significantly more ICH events and deaths compared to apixaban alone.
- For individuals aged 75 and older, apixaban alone was consistently the preferred strategy.
- Results were sensitive to the lecanemab-anticoagulant interaction on ICH risk and lecanemab's effect on cognition.
Conclusions:
- Anticoagulant therapy alone is the preferred strategy for patients aged 75 and older with early AD and AF.
- For patients aged 65-74, the optimal strategy remains uncertain and depends critically on precise estimates of ICH risk associated with lecanemab-anticoagulant interactions.
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).
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