Upstream targeting for the prevention of atrial fibrillation: Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF)-rationale and study design
Files
(Published version)
Date
2025
Authors
Wass, S.Y.
Barnard, J.
Kim, H.S.
Sun, H.
Telfer, W.
Schilling, T.
Barzilai, B.
Bruemmer, D.
Cho, L.
Huang, J.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Interventional Cardiac Electrophysiology, 2025; 68(1):9-19
Statement of Responsibility
Sojin Y. Wass, John Barnard, Hyun Su Kim, Han Sun, William Telfer, Taylor Schilling, Benico Barzilai, Dennis Bruemmer, Leslie Cho, Julie Huang, Ayman Hussein, Sangeeta R. Kashyap, Luke Laffin, Reena Mehra, Chris Moravec, Walid Saliba, Prashanthan Sanders, Steven Nissen, Niraj Varma, Jonathan Smith, David Van Wagoner, Mina K. Chung
Conference Name
Abstract
BACKGROUND: Despite advances in ablation and other therapies for AF, progression of atrial fibrillation (AF) remains a significant clinical problem, associated with worse prognosis and worse treatment outcomes. Upstream therapies targeting inflammatory or antifibrotic mechanisms have been disappointing in preventing AF progression, but more recently genetic and genomic studies in AF suggest novel cellular and metabolic stress targets, supporting prior studies of lifestyle and risk factor modification (LRFM) for AF. However, while obesity is a significant risk factor, weight loss and risk factor modification have not been successfully applied in a US population with AF. Metformin, a common drug that targets metabolic stress pathways, has demonstrated potential in reducing the burden of AF. METHODS: The Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF, NCT03603912) is a randomized clinical trial designed to examine reduction of AF burden and progression, targeting metabolic upstream therapies. This single center trial, at the Cleveland Clinic, is designed as a prospective randomized open-label blinded endpoint (PROBE) 2 × 2 factorial study of metformin extended release up to 750 mg twice daily and lifestyle and risk factor modification (LRFM) in patients with a cardiovascular implantable electronic device (CIED) that have had at least one ≥ 5-min episode of atrial fibrillation (AF) over the prior 3 months. Randomization is stratified by pacemaker vs. ICD and rhythm at enrollment (sinus rhythm/atrial paced vs. AF). CONCLUSION: TRIM-AF trial aims to determine if metformin, lifestyle, and risk factor modification (LRFM) reduce AF burden and its progression and assess whether combined therapy outperforms individual treatments. TRIAL REGISTRATION: URL: https://clinicaltrials.gov/ ; Unique Identifier: NCT03603912.
School/Discipline
Dissertation Note
Provenance
Description
Published: 13 December 2024
Access Status
Rights
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.