Upstream targeting for the prevention of atrial fibrillation: Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF)-rationale and study design.

IF 2.1 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of Interventional Cardiac Electrophysiology Pub Date : 2024-12-13 DOI:10.1007/s10840-024-01955-z

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

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引用次数: 0

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.

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来源期刊

Journal of Interventional Cardiac Electrophysiology 医学-心血管系统

CiteScore

4.30

自引率

11.10%

发文量

320

审稿时长

4-8 weeks

期刊介绍： The Journal of Interventional Cardiac Electrophysiology is an international publication devoted to fostering research in and development of interventional techniques and therapies for the management of cardiac arrhythmias. It is designed primarily to present original research studies and scholarly scientific reviews of basic and applied science and clinical research in this field. The Journal will adopt a multidisciplinary approach to link physical, experimental, and clinical sciences as applied to the development of and practice in interventional electrophysiology. The Journal will examine techniques ranging from molecular, chemical and pharmacologic therapies to device and ablation technology. Accordingly, original research in clinical, epidemiologic and basic science arenas will be considered for publication. Applied engineering or physical science studies pertaining to interventional electrophysiology will be encouraged. The Journal is committed to providing comprehensive and detailed treatment of major interventional therapies and innovative techniques in a structured and clinically relevant manner. It is directed at clinical practitioners and investigators in the rapidly growing field of interventional electrophysiology. The editorial staff and board reflect this bias and include noted international experts in this area with a wealth of expertise in basic and clinical investigation. Peer review of all submissions, conflict of interest guidelines and periodic editorial board review of all Journal policies have been established.