GLP-1 Drugs Make Promising Debut in TAVR, Carotid Artery Stenting

Cardiovascular protection with GLP-1 receptor agonists may benefit patients undergoing certain transcatheter procedures, according to two observational studies.

When used as an adjunct to transcatheter aortic valve replacement (TAVR), tirzepatide (Mounjaro, Zepbound) reduced heart failure (HF) events in the 1 year after the procedure, reported Ibrahim Mortada, MD, of the University of Texas Medical Branch at Galveston, and colleagues.

Separately, major adverse cardiovascular events (MACE) at 1 year were also significantly reduced among GLP-1 drug users undergoing carotid artery stenting (CAS), reported Abdullah Ghuman, MD, and Maumita Das, MD, both of TidalHealth Peninsula Regional in Salisbury, Maryland.

Both studies were presented at the Society for Cardiovascular Angiography and Interventions (SCAI) annual meeting in Montreal and published in JSCAI.

GLP-1 receptor agonists are a recently established medication class for cardiovascular risk reduction beyond glycemic control and weight loss. These new findings thus potentially extend the cardiovascular benefits of these drugs to populations with high-risk structural heart and carotid revascularization.

Tirzepatide and TAVR

In the TAVR study, tirzepatide had benefits that appeared specific to HF and renal pathways without a broad effect on atherosclerotic events.

Tirzepatide was associated with reduced HF events when initiated in the 1 year after TAVR, with patients prescribed the dual GIP/GLP-1 drug having fewer events versus non-users (44.9% vs 55.3%, HR 0.68, 95% CI 0.56-0.83). What’s more, there was also a signal of reduced acute kidney injury in these patients (9.7% vs 17.1%, HR 0.63, 95% CI 0.43-0.93), Mortada and colleagues reported.

Meanwhile, there were no improvements in acute myocardial infarction (MI; 5.7% vs 8.1%, HR 0.81, 95% CI 0.48-1.37) or ischemic stroke (6.7% vs 10.5%, HR 0.73, 95% CI 0.45-1.17).

“Importantly, the persistence of HF and cardiorenal events after TAVR likely reflects underlying metabolic dysfunction rather than body size alone, highlighting the need for adjunctive therapies targeting cardiometabolic pathways rather than weight classification alone,” the authors wrote.

“Taken together, these findings support the hypothesis that metabolic optimization may represent an important adjunctive strategy in the care of patients with obesity undergoing TAVR,” they concluded. “As TAVR expands into younger and lower-risk populations with a high prevalence of metabolic disease, the role of adjunctive cardiometabolic therapies warrants further investigation.”

GLP-1 Drugs After Carotid Artery Stenting

GLP-1 receptor agonists also showed promise as adjunctive therapy in patients undergoing carotid revascularization.

Rates of MACE at 1 year — counting MI, cerebral infarction, and all-cause mortality — were significantly lower in patients undergoing CAS who had GLP-1 medication exposure before or after the procedure (39.7% vs 44.6% for nonexposed peers, risk ratio [RR] 0.89, 95% CI 0.80-0.99), reported Ghuman and Das.

“To our knowledge, data evaluating GLP-1 RA [receptor agonist] therapy specifically in CAS populations are limited, and this analysis provides initial observational evidence in this high-risk population,” they wrote. “These findings are hypothesis-generating and warrant prospective evaluation in carotid revascularization populations.”

The authors highlighted the persistently elevated periprocedural stroke or death rates with CAS compared with carotid endarterectomy in symptomatic patients.

“Given the high burden of polyvascular atherosclerosis in patients undergoing CAS, and the unique periprocedural stroke risk related to embolic phenomena during plaque manipulation, GLP-1 RAs may represent a biologically plausible adjunct for reducing postprocedural cardiovascular events,” they noted. “GLP-1 RAs’ demonstrated effects on plaque stabilization, inflammation, and endothelial function may be particularly relevant in this population.”

Of note, the benefit with GLP-1 drugs after CAS was driven by a particularly large reduction in all-cause mortality (3.9% vs 8.9%, RR 0.44, 95% CI 0.30-0.64), whereas the difference in MI (8.6% vs 9.2%, RR 0.93, 95% CI 0.69-1.25) and cerebral infarction (32.4% vs 35.3%, RR 0.92, 95% CI 0.81-1.05) did not individually reach statistical significance.

“Our study may have been underpowered to detect differences in individual ischemic components, particularly given the modest effect sizes observed (RR 0.92-0.93),” Ghuman and Das wrote. “Additionally, the 1-year follow-up period may be insufficient to observe the full anti-atherosclerotic effects of GLP-1 RA therapy.”

It is also possible that the mechanisms of benefit are unrelated to atherothrombotic protection after all.

Study Details

Both retrospective studies used electronic health record (EHR) data from the TriNetX Global Collaborative Network.

The study by Mortada and colleagues included adults with obesity who underwent TAVR from 2020 to 2025, split between initiators of tirzepatide after TAVR (defined as any documented prescription; n=437) and non-users (n=12,406).

Propensity score matching yielded comparable cohorts of 421 individuals each. These matched cohorts had a mean age just under 73 years, about 90% were white, and patients were roughly split between the sexes. Just over 70% had diabetes, and nearly three in four had obesity. Residual imbalance persisted for anticoagulant use (56.5% with tirzepatide vs 62.2% without) and antilipemic therapy (67.9% vs 72.7%).

As for the other study, Ghuman and Das included 906 adults undergoing CAS from 2015 to 2023 who had GLP-1 drug exposure, defined as at least one prescription of semaglutide (Ozempic, Wegovy), liraglutide (Victoza, Saxenda), lixisenatide (Adlyxin), or tirzepatide within 12 months of the procedure, and 29,476 controls undergoing CAS with no such exposure.

Propensity score matching yielded 899 matched pairs; baseline characteristics were mostly comparable except the GLP-1 drug group had a higher body mass index and hemoglobin A1c values even after matching. Type 2 diabetes was present in about 88% of the cohort, obesity in 53%, and prior cerebral infarction in nearly half.

The two observational studies left residual confounding a possibility, and the reliance on hospital-based records was a potential source of selection bias. Both studies used prescription data as a proxy for GLP-1 drug use without being able to account for actual medication adherence.

Ghuman and Das also noted that they could not distinguish between pre- and post-procedural initiators of GLP-1 drugs and had to exclude dulaglutide (Trulicity) and exenatide due to EHR database limitations.

“The higher-than-expected MACE rate may also reflect a predominantly symptomatic population or those with high-risk plaque features, which the TriNetX platform cannot adjudicate,” Ghuman and Das added. “Whether GLP-1 RA benefits differ between symptomatic versus asymptomatic patients, or those with versus without prior cerebrovascular events, remains unknown and warrants investigation in future prospective studies with adequate power for subgroup analyses.”