Research News

Atrial fibrillation (AF) is the most common type of heart arrhythmia and is estimated to affect more than 12 million people by 2030. Cleveland Clinic researchers are leading nationwide studies to answer one of the biggest questions about how to prevent AF: how to reach and treat the root causes of the disease. 

Lifestyle changes, such as weight loss and exercise, have been reported to decrease the risk and slow the progression of AF. Targeted therapeutics have the potential to address the specific mechanisms that initiate and promote the disease. No new drugs have been approved in more than a decade for AF. The TRIM-AF trial, launched in 2018 and led by Cleveland Clinic cardiologist and researcher Mina Chung, MD, sought to answer whether the drug metformin and/or lifestyle and risk factor modification could target AF’s underlying factors. 

Dr. Chung and David Van Wagoner, PhD, department of Cardiovascular & Metabolic Sciences, a collaborator who also works on the TRIM-AF trial, were on the committee that wrote the 2023 American College of Cardiology/American Heart Association’s AF diagnosis and management guidelines. They shared insight into initial results from TRIM-AF and next steps for their research. 

How does the research build on current atrial fibrillation guidelines? 

Current AF guidelines recognize lifestyle and risk factor modification as the gold standard for treatment to prevent arrhythmia onset, progression and adverse outcomes. Previous studies have documented the benefits of encouraging physical activity, smoking cessation and controlling blood pressure and obesity. However, current drugs used to treat AF aren’t very effective, and lifestyle changes can be difficult to achieve, Dr. Van Wagoner says.  

"The Cleveland Clinic research team is investigating drugs that could work alongside lifestyle changes to prevent AF. Lifestyle changes are still the main way that patients would work to reverse or prevent AF," Dr. Chung says. 

Why investigate metformin? 

After researching eight other candidate drugs, TRIM-AF researchers identified metformin as the most promising medication to treat AF. Metformin, a well-established drug used for diabetes, shows additional benefits in weight management or loss, one of the primary recommendations for treating or preventing AF. The drug has also been shown to increase lifespan in preclinical models. 

Metformin can prevent insulin resistance in muscle and improve the metabolic function of mitochondria (a cell’s energy source) in the heart. The research team hypothesized that improving heart muscle metabolism would help to decrease the burden of atrial fibrillation. 

What are the initial results of the TRIM-AF trial? 

The clinical trial measured outcomes for four groups: metformin and lifestyle and risk factor management, metformin-only, lifestyle and risk factor management only and standard of care. The initial results of the study after one year of follow-up show that the metformin did not significantly lessen the burden of AF. Instead, the study showed that in the standard of care arm, where subjects received written information about lifestyle changes and risk factor management, AF burden was lessened more than with metformin alone, and slightly more than the active lifestyle and risk factor modification arm over the first year of follow-up.  

“At this time, metformin cannot be recommended as an upstream therapy for AFib,” Dr. Chung says. “But we may have more influence over our patients than we sometimes think. It’s important to talk about lifestyle and give patients guidance, and maybe just that will be helpful.” 

Why is it critical to look for new therapeutics to prevent AF? 

Research is ongoing to complete the two-year follow-up and to analyze both the clinical data and biological samples collected during the TRIM-AF trial, to better understand the factors that contribute to AF burden.  

In collaboration with Feixiong Cheng, PhD, and John Barnard, PhD, the group is identifying other potential candidate drugs using artificial intelligence methods to analyze genomic and genetic networks and test their findings in lab-grown cells and heart tissues. There is also a focus on potential metabolic regulators that might affect AF burden, including drugs that can help with weight loss.