GLP-1 Drugs May Lower CV Risk in TAVI Patients With Diabetes or Obesity

Glucagon-like peptide-1 (GLP-1) receptor agonists may improve cardiovascular outcomes in the year following TAVI for aortic stenosis in patients with diabetes or obesity, according to new real-world data.

The new findings, published online last week in the Canadian Journal of Cardiology with first author Aman Goyal, MD (Cleveland Clinic Foundation, OH), show that GLP-1 receptor agonist use among 1,708 propensity-matched TAVI patient pairs was associated with a 37% lower relative risk of MACE at 1 year and 39% lower relative risk of all-cause mortality.

“Patients who are undergoing TAVI are at an elevated cardiovascular risk because of the milieu or the protoplasm or because of their baseline risk factors,” senior investigator Arman Qamar, MD, MPH (Endeavor Health Cardiovascular Institute, Glenview, IL), told TCTMD. “Of course, the TAVI plays a major role in improving their outcomes, but there’s still a room for improvement in these patients.”

Earlier this year, the small TAVR-MET trial showed that tirzepatide (Zepbound; Eli Lilly) given before TAVI was linked with a reduced risk of subclinical leaflet thrombosis and paravalvular leak (PVL) within 1 year. Other analyses looking at this class of drugs have demonstrated reductions in weight, fewer CV events, vascular benefits, and more, with experts calling for increased adoption within cardiology.

“The general population typically thinks of a GLP-1 receptor agonist as really just a weight loss drug, which is not true,” Qamar added. “In the cardiovascular community, we really look at these agents as cardiovascular risk modifiers.”

A.M. Thirugnanam, MD (Ipcard Cardiac Care Center, Hyderabad, India), one of the TAVR-MET researchers, told TCTMD that the data should affect follow-up care pathways for these patients.

“This is an important and timely study highlighting the potential role of GLP-1 receptor agonists in improving cardiovascular outcomes among patients with diabetes or obesity undergoing TAVR,” he said in an email. “The findings suggest that post-TAVR care should extend beyond valve replacement to comprehensive cardiometabolic optimization.”

Fewer MACE With GLP-1s

The study is an analysis of more than 21,000 TAVI patients with type 2 diabetes or obesity from the TriNetX database who were treated in the US between 2020 and 2025. In total, 10.4% were GLP-1 receptor agonist users, defined as having documentation in their electronic health record medication list either 3 months before or any time after TAVI.

Propensity-score matching enabled the comparison of 1,708 pairs who used GLP-1 receptor agonists or who did not.

The composite primary endpoint of MACE—defined as all-cause mortality, acute MI, stroke, and heart failure exacerbation at 1 year—occurred in 35.4% of GLP-1 users and 48.9% of nonusers (HR 0.63; 95% CI 0.57-0.70). Individual risks of all-cause mortality (HR 0.61; 95% CI 0.48-0.78), acute MI (HR 0.71; 95% CI 0.57-0.89), stroke (HR 0.74; 95% CI 0.59-0.94), heart failure exacerbation (HR 0.38; 95% CI 0.32-0.44), and new-onset atrial fibrillation/flutter (HR 0.60; 95% CI 0.44-0.84) were also lower with GLP-1 use.

These findings held true in subgroup analyses looking only at patients with type 2 diabetes but not obesity as well as those with obesity but not type 2 diabetes.

Given the constraints of the data, Qamar acknowledged that “these findings do not confirm causality.” However, the study “encourages us to do a more prospective study,” he added.

The ongoing phase III REVERSE-TAVR trial, Qamar noted, should provide more information about whether TAVI patients at high cardiometabolic risk benefit from semaglutide (Wegovy; Novo Nordisk) compared with placebo.

“GLP-1 receptor agonists may become an important adjunctive therapy in selected high-risk TAVR patients, but prospective randomized trials are essential before routine post-TAVR recommendation,” Thirugnanam agreed.

For now, Qamar said, “I hope our findings will provide more encouragement to physicians” in treating patients slated for TAVI with GLP-1s. “Weight loss is a very small part of what they do—they lower inflammation, they improve lipid markers, they improve blood pressure, [and] they probably have some benefit on the myocardial parameters,” he noted.

Research is only beginning to uncover how GLP-1s can benefit cardiovascular patients, Qamar concluded. “This field is just wide open for investigation,” he said. “We are looking at TAVI now, but I think the care for patients with structural heart disease does not stop in the cath lab.”