GLP-1 receptor agonist use and long-term outcomes in hypertrophic cardiomyopathy with obstructive sleep apnoea: A real-world cohort analysis

Obstructive sleep apnoea (OSA) is prevalent in hypertrophic cardiomyopathy (HCM) and may contribute to adverse cardiometabolic and cardiovascular outcomes. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for cardiometabolic risk management, their association with long-term outcomes in adults with HCM and OSA remains unclear. To evaluate the association between GLP-1 RA exposure and long-term clinical outcomes in adults with HCM and OSA. We performed an observational cohort study using the TriNetX Global Collaborative Network. Adults (≥18 years) with HCM (ICD-10 I42.1/I42.2) and OSA (ICD-10 G47.33) were identified. Exposure was GLP-1 RA use after HCM diagnosis; the comparator cohort had no GLP-1 RA use. Patients with prior heart transplant, septal reduction therapy, or myectomy were excluded. Propensity score matching (1:1) was performed across 18 covariates (including age, sex, body mass index, and comorbidities). Outcomes were assessed from day 1 after cohort entry and continued up to 5,475 days (~15 years). The primary outcome was major adverse cardiovascular events (MACE: all-cause mortality, acute myocardial infarction, ischaemic stroke). Secondary outcomes were acute heart failure hospitalisation and arrhythmias (atrial fibrillation/flutter, ventricular fibrillation, ventricular tachycardia). Baseline characteristics after matching are shown in Figure 1a. Before matching, cohort sizes were 4,962 (GLP-1 RA) and 36,249 (no GLP-1 RA); after matching, 4,930 patients were included in each cohort. For MACE (excluding patients with a prior outcome for risk estimates), cumulative risk was 10.0% vs 15.4% (odds ratio 0.61; absolute risk difference −5.4%; p<0.0001). In time-to-event analysis (Figure 1b), the MACE hazard ratio (HR) was 0.64 (95% CI 0.59–0.71; log-rank p<0.0001), with MACE-free survival at 5,475 days of 54.3% vs 31.7%. For acute heart failure hospitalisation (excluding prior such events), cumulative risk was 4.7% vs 5.1% (odds ratio or OR 0.92; p=0.40); Cox proportional HR was 0.84 (95% CI 0.70–1.02; log-rank p=0.08). For arrhythmias (excluding prior events), cumulative risk was 12.8% vs 11.2% (OR 1.16; p=0.04); Cox proportional HR was 1.07 (95% CI 0.93–1.23; log-rank p=0.38). In this large real-world cohort of adults with HCM and OSA, GLP-1 RA exposure was associated with lower odds of MACE and improved long-term MACE-free survival. No statistically significant difference was observed for acute heart failure hospitalisations. Prospective studies are warranted to confirm these associations.