# Metabolic therapy for atrial fibrillation

> **NIH NIH R21** · CLEVELAND VA MEDICAL RESEARCH/ED/FDN · 2024 · $100,050

## Abstract

Atrial Fibrillation (AF) is the most common arrhythmia in the United States (US) with an estimated prevalence of
5 million and is expected to increase to 12 million by 2030. AF poses a substantial public health burden in the
US with an estimated annual cost of $6 billion. AF is associated with an increased risk of stroke, heart failure,
cardiovascular mortality, and significantly impairs quality of life in most patients.
 Restoration and maintenance of sinus rhythm with antiarrhythmic agents and catheter ablation remains the
cornerstone treatment in symptomatic AF patients. The long-term recurrence of AF with anti-arrhythmic agents
remains unacceptably high and moreover, their safety profile is suboptimal as they have a narrow therapeutic
window. While catheter ablation is more effective in restoring sinus rhythm, the recurrence rates following
ablation still ranges from 30% to 50% in persistent AF, often leading to a second procedure.
 AF is a progressive disease with many patients progressing from paroxysmal AF to persistent AF and
eventually longstanding persistent AF leading to permanent AF. Whilst this observation was initially considered
to be part of the arrhythmic process, recent data suggest that the likelihood of progression to more persistent
forms of AF, are determined by uncontrolled cardiometabolic risk factors including obesity, diabetes mellitus
(DM), metabolic syndrome, alcohol abuse and hypertension. Recently, several studies have reported positive
impact of cardiometabolic risk factor modification with incident AF (primary prevention), but fewer studies have
examined the relationship with the burden of AF in patients with pre-existing AF (secondary prevention).
 These findings suggest that a new paradigm for AF management (primary and secondary prevention) should
include a new pillar targeting lifestyle and cardiometabolic risk factors. There have been significant recent
advances in the development of cardiometabolic drugs, which are FDA-approved to treat metabolic conditions
such as obesity and DM. There is a critical need to investigate the clinical effectiveness of management of
cardiometabolic risk factors with new cardiometabolic drugs including Glucagon-Like Peptide 1 Receptor
Agonists (GLP1-RA) and Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) in secondary prevention of AF.
 Accordingly, we aim to we perform comparative effectiveness research investigating the role of new
cardiometabolic agents including GLP-1RA, SGLT2i and repurposing potential of metformin alongside bariatric
surgery in reduction of AF burden. We will be using the Veteran Affairs nationwide electronic healthcare records
(VA-EHR) which provides a unique opportunity to perform CER of AF at the population level due to the availability
of long term follow data (> 600,000 AF patients with ~7 years of follow up) with minimal missingness in follow
up. The results from this R21 are likely to yield substantive new insights into the role of cardiometabolic ...

## Key facts

- **NIH application ID:** 10975588
- **Project number:** 1R21HL170269-01A1
- **Recipient organization:** CLEVELAND VA MEDICAL RESEARCH/ED/FDN
- **Principal Investigator:** Jayakumar Sahadevan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $100,050
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10975588

## Citation

> US National Institutes of Health, RePORTER application 10975588, Metabolic therapy for atrial fibrillation (1R21HL170269-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10975588. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
