Cardiovascular Outcomes with GLP-1 Receptor Agonists in Patients with Type 2 Diabetes or Obesity Undergoing Surgical Aortic Valve Replacement
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Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular benefit in type 2 diabetes and obesity, with recent observational data suggesting favorable associations after transcatheter aortic valve replacement. Whether similar associations exist after surgical aortic valve replacement (SAVR) is unknown.
Methods
Retrospective propensity-matched cohort analysis using the TriNetX U.S. Collaborative Network. Adults with type 2 diabetes or obesity (BMI ≥30 kg/m²) undergoing SAVR were categorized by GLP-1 RA exposure (any use within 3 months before through 1 year after SAVR) versus no use. One-to-one matching was performed on 44 covariates. Primary outcomes were 1-year all-cause mortality, heart failure, acute kidney injury, acute myocardial infarction, cerebral infarction, and atrial fibrillation. Sensitivity analyses included 30-day landmark restriction and falsification outcomes.
Results
After matching, 1,984 patients were retained per cohort. GLP-1 RA use was associated with lower 1-year risks of all-cause mortality (4.8% vs 10.4%; HR, 0.44; 95% CI, 0.34–0.56), acute kidney injury (6.9% vs 10.1%; HR, 0.65; 95% CI, 0.49–0.85), myocardial infarction (3.0% vs 5.1%; HR, 0.57; 95% CI, (0.40–0.82), heart failure (11.3% vs 15.7%; HR, 0.68; 95% CI, (0.51–0.90), and atrial fibrillation or flutter (10.1% vs 13.9%; HR, 0.69; 95% CI, 0.54–0.90; all P≤.006). Cerebral infarction did not differ. In landmark analysis, mortality, heart failure, and acute kidney injury associations persisted; myocardial infarction and atrial fibrillation associations were attenuated. Falsification outcomes were null.
Conclusions
Perioperative GLP-1 RA use was associated with lower 1-year cardiovascular event rates after SAVR. These hypothesis-generating findings support prospective randomized investigation.
Clinical Perspective
What Is New?
– This is the first analysis to evaluate the association between GLP-1 receptor agonist use and cardiovascular outcomes specifically in patients undergoing surgical aortic valve replacement, extending prior observations from the transcatheter aortic valve replacement literature to a distinct surgical population.
– Perioperative GLP-1 receptor agonist use was associated with significantly lower 1-year risks of all-cause mortality, heart failure, and acute kidney injury, and these associations persisted after 30-day landmark restriction. Associations with acute myocardial infarction and new-onset atrial fibrillation were attenuated to null after landmark restriction, indicating these signals were predominantly driven by peri-procedural events.
What Are the Clinical Implications?
– These hypothesis-generating findings suggest that GLP-1 receptor agonists may have a role as adjunctive perioperative cardioprotection in patients with type 2 diabetes or obesity undergoing surgical aortic valve replacement, though the observed effect magnitudes exceed those from randomized trials and residual confounding cannot be excluded.
– Prospective randomized investigation is needed to determine whether GLP-1 receptor agonist therapy confers genuine cardiovascular benefit in this population and to identify optimal timing of initiation relative to surgery.
