BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a well-established, genetically mediated risk factor for atherosclerotic cardiovascular disease (ASCVD), yet effective therapies targeting Lp(a) remain limited. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide cardiometabolic benefits in high-risk populations, but their impact among patients with elevated Lp(a) levels is not well defined.
METHODS: We conducted a retrospective cohort study to evaluate cardiovascular outcomes associated with GLP-1RA therapy in adults with Lp(a) >50 mg/dL and comorbid obesity or type 2 diabetes. Patients were categorized into GLP-1RA users versus non-users and matched 1:1 using propensity scores based on demographics, cardiovascular risk factors, and baseline comorbidities. The primary outcome was all-cause mortality; secondary outcomes included major adverse cardiovascular events (MACE: myocardial infarction, ischemic stroke, and coronary revascularization). Hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards models.
RESULTS: Among 24,185 eligible patients, 3791 received a GLP-1RA. After matching, 3310 patients remained in each cohort with balanced baseline characteristics. Over a median follow-up of approximately two years, GLP-1RA use was associated with significantly lower all-cause mortality (HR 0.66, 95% CI 0.48-0.90) and reduced MACE (HR 0.68, 95% CI 0.60-0.76). Individual components, including myocardial infarction, ischemic stroke, and cardiovascular death, were also significantly decreased among GLP-1RA users.
CONCLUSION: In patients with elevated Lp(a), GLP-1RA therapy was associated with substantial reductions in mortality and cardiovascular events. These findings suggest potential cardioprotective effects of GLP-1RAs in a high-risk population with limited therapeutic options and support further prospective evaluation.
