# Effectiveness and Safety of Transcatheter Left Atrial Appendage Occlusion vs. Anticoagulation in Older Adults with Atrial Fibrillation and Alzheimer's Disease and Related dementias

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $719,578

## Abstract

Project Summary
Non-valvular atrial fibrillation (AF) is highly prevalent in older adults and associated with a 5-fold increased risk
of cardioembolic stroke. Oral anticoagulants (OACs) can reduce this risk by ~70%, but nearly 50% of such older
patients are not anticoagulated, with Alzheimer’s disease and related dementias (ADRD) being among the
leading cited reasons, attributed to a higher risk of falls, medication errors, and poor adherence. Since the vast
majority of thrombus formation in AF occurs in the left atrial appendage, transcatheter left atrial appendage
occlusion (LAAO) has been approved in the US since 2015 as a one-time procedural alternative treatment for
stroke prevention in AF patients with high risks of complications from OACs. The uptake of transcatheter LAAO
has been growing at a rate of 2 to 3-fold yearly, and it is clearly changing the prescribing pattern of OACs in AF
patients. However, our pilot data showed persons living with dementia (PLWDs) are significantly less likely to
receive transcatheter LAAO when it is indicated. One likely barrier is that PLWDs and frail older adults were
much under-represented in the randomized controlled trials (RCTs) which led to transcatheter LAAO approval.
Also, several high-risk characteristics prevalent in PLWDs, including frailty, dementia severity, fall risks, and
advanced kidney disease, are risk factors for both the transcatheter LAAO procedure-related complications and
bleeding risks from OACs, complicating the prescribing decisions. Thus, there is an urgent need to investigate
the net clinical benefit, weighing the benefits of stroke prevention against the major bleeding and procedure
complications, comparing transcatheter LAAO with specific OACs in PLWDs. Our objective is to establish a
prospective monitoring program in 3 large national healthcare utilization databases (Medicare, IBM Marketscan,
and Optum claims data, covering ~15 million lives) from 2015-2025, linked to electronic health records (EHR).
We will evaluate treatment outcomes of transcatheter LAAO vs. specific OACs in PLWDs with AF with detailed
treatment effect heterogeneity evaluation by frailty, dementia severity, fall risks, advanced kidney disease, and
patient-reported and family factors. We will also determine the utilization trends, predictors, and barriers of
transcatheter LAAO and OACs in PLWDs, using a novel signal detection tool, TreeScan, developed by the
applicant team and adopted by the US Food and Drug Administration for prospective drug safety monitoring.
Our central hypothesis is that transcatheter LAAO has a favorable long-term net clinical benefit compared with
OACs in PLWDs and the relative benefits vary by specific identifiable clinical factors. This proposal will yield: 1)
direct benefit-to-risk data to inform the use of transcatheter LAAO and specific OACs for stroke prevention in
PLWDs with AF; 2) a novel and generalizable prospective monitoring program that compares effectiveness and
safety o...

## Key facts

- **NIH application ID:** 10443345
- **Project number:** 1R01AG075335-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** JOSHUA K LIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $719,578
- **Award type:** 1
- **Project period:** 2022-08-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443345

## Citation

> US National Institutes of Health, RePORTER application 10443345, Effectiveness and Safety of Transcatheter Left Atrial Appendage Occlusion vs. Anticoagulation in Older Adults with Atrial Fibrillation and Alzheimer's Disease and Related dementias (1R01AG075335-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10443345. Licensed CC0.

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