Glucagon-like peptide receptor agonists (GLP-1RAs) as cardiovascular risk modifiers in obstructive sleep apnea and obesity: a real-world study

INTRODUCTION: Obstructive sleep apnea (OSA) is a well-established risk factor for cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated potential in reducing cardiovascular risk and improving OSA severity. However, a significant knowledge gap remains regarding the impact of GLP-1RAs on cardiovascular events in OSA patients. METHODS: We examined patients with a BMI over 30 diagnosed with OSA between January 2010 and November 2021 without a previous diagnosis of heart failure, pulmonary hypertension, or myocardial infarction. Two cohorts were created: those prescribed GLP-1RAs within 1 year of their OSA diagnosis and patients who were never prescribed GLP-1RAs. Propensity score matching was performed using TriNetX software with greedy nearest neighbor methodology. Cox proportional hazards analyses were conducted over a 3-year follow-up period. The primary outcome was newly diagnosed heart failure. Secondary outcomes included pulmonary hypertension, death from all causes, ischemic stroke, and acute myocardial infarction (AMI). RESULTS: We included 18,774 patients in the GLP-1RA cohort and 847,137 patients in the non-GLP-1RA cohort. Propensity score matching resulted in 18,523 patients remaining in each cohort, which were well-matched in demographics, comorbidities, medications, BMI, and HbA1c. After 3 years, the GLP-1RA cohort had a significantly lower risk of newly developed heart failure (HR, 0.76; 95% CI, 0.71-0.82), pulmonary hypertension (HR, 0.67; 95% CI, 0.59-0.75), AMI (HR, 0.76; 95% CI, 0.67-0.86), and death from all causes (HR, 0.57; 95% CI, 0.51-0.63). CONCLUSION: GLP-1RAs were associated with reduced risks of heart failure, pulmonary hypertension, AMI, and death from all causes in obese OSA patients. Prospective studies are needed for validation. GLP-1 receptor agonists (GLP-1RAs) have shown promising potential in reducing cardiovascular risk and alleviating the severity of obstructive sleep apnea (OSA), a well-known risk factor for cardiovascular disease. However, a significant knowledge gap remains regarding the impact of GLP-1RAs on cardiovascular events specifically in patients with OSA. With 3 years of follow-up, the GLP-1RAs reduced newly developed heart failure by 24%, pulmonary hypertension by 33%, acute myocardial infarction by 24%, and death by 43%, with notable early separation in heart failure and all-cause mortality. This finding supports the potential for broader use of GLP-1RAs in this population, not only to improve OSA severity, but also to reduce cardiovascular risk.