BACKGROUND: GLP-1 (glucagon-like peptide-1) receptor agonists (GLP-1RAs), initially developed for glycemic control in type 2 diabetes, have shown cardiometabolic benefits including weight loss, improved endothelial function, and reduced inflammation. Recent data suggest potential anti-arrhythmic effects via modulation of atrial substrate and autonomic tone. Their impact on obese, nondiabetic patients remains underexplored. This study examines whether GLP-1RA use is associated with reduced atrial fibrillation recurrence after catheter ablation in obese patients, using real-world data from a large multicenter database. METHODS: We conducted a retrospective cohort study using the TriNetX research network, which contains de-identified electronic health records from >100 million patients. Adult patients (age ≥18 years) with obesity (body mass index >30 kg/m²) who underwent atrial fibrillation (AF) ablation between January 2015 and January 2025 were eligible. The cohort was divided into GLP-1RA users (n=3350) and nonusers (n=3350), with 1:1 propensity score matching performed across 82 clinical and demographic variables, including age, sex, race, AF subtype, cardiovascular comorbidities, and baseline medications. RESULTS: During a median follow-up of 2 years (interquartile range, 0.8–3.2) AF recurrence was significantly lower in GLP-1RA users versus non users (6.66% versus 7.72%; hazard ratio [HR], 0.82 [95% CI, 0.76–0.88]; P <0.0001) Progression to permanent AF occurred less frequently in GLP-1RA users (3.16% versus 3.38%; HR, 0.77 [95% CI, 0.63–0.93]; P =0.01). Risk of all-cause mortality was lower in the GLP-1RA group (HR, 0.73 [95% CI, 0.59–0.91]; P =0.01) HF hospitalization (HR, 0.80 [95% CI, 0.71–0.90]; P <0.0001) and cardiovascular hospitalizations (HR, 0.85 [95% CI, 0.77–0.93]; P =0.001) were also significantly lower with GLP-1RA use. No significant difference was found for redo ablation. CONCLUSIONS: In a large real-world cohort of obese patients undergoing catheter ablation for AF, GLP-1RA therapy was associated with lower risks of AF recurrence, progression to permanent AF, cardiovascular hospitalizations, and mortality.

BACKGROUND: GLP-1RAs (glucagon-like peptide-1 receptor agonists) have consistently demonstrated a protective effect against ischemic stroke. However, whether this benefit also extends to nontraumatic intracerebral hemorrhage (ICH) remains unknown. Given the blood pressure–lowering and anti-inflammatory properties of GLP-1RAs, we aimed to evaluate their potential impact on ICH risk in patients with type 2 diabetes. METHODS: We conducted a retrospective cohort study using global health care data from the TriNetX network. Patients with type 2 diabetes who used GLP-1RAs (n=326 777) were compared with those who did not (n=643 614). Propensity score matching (1:1) was performed to balance baseline characteristics, and follow-up was conducted for up to 4 years. The primary outcomes included all-cause mortality, ischemic stroke, and ICH (overall and by location). Hazard ratios and 95% CIs were calculated to assess the mean treatment effect in the treated group. RESULTS: After propensity score matching (resulting in 2 balanced groups of 255 460 individuals each), GLP-1RAs use was associated with a lower risk of ICH (hazard ratio, 0.743 [95% CI, 0.684–0.807]). The lower ICH risk associated with GLP-1RAs was observed across all ICH locations (all P ≤0.01). In addition, exposure to GLP-1RAs was associated with a significantly lower rate of mortality (hazard ratio, 0.525 [95% CI, 0.512–0.538]) and ischemic stroke (hazard ratio, 0.871 [95% CI, 0.843–0.901]). CONCLUSIONS: This study highlights a novel potential association between GLP-1RAs and a lower risk of ICH in patients with type 2 diabetes. Prospective studies and future trials are needed to confirm the potential protective effect of GLP-1RAs on small vessel rupture.

Background: Atrial fibrillation (AF) patients represent a clinically complex, heterogeneous population comprising multiple homogeneous cohorts. Purpose: We aimed to identify the common clinical phenotypes of AF patients and compare clinical outcomes between these subgroups. Methods: A 1% representative sample of all AF patients hospitalized between 2010 and 2019 was identified from the French national database. Agglomerative hierarchical cluster analysis was performed using Ward’s method and squared Euclidian distance to derive the clusters of patients. Cox regression analyses were used to evaluate outcomes including all-cause death, cardiovascular death, non-cardiovascular death, ischemic stroke, hospitalization for heart failure (HF) and composite of ventricular tachycardia, ventricular fibrillation and cardiac arrest (VT/VF/CA) over a mean follow-up period of 2.0 ± 2.3 years. Results: Four clusters were generated from the 12,688 patients included. Cluster 1 (n = 2375) was younger, low cardiovascular disease (CVD)-risk group with a high cancer prevalence. Clusters 2 (n = 6441) and 3 (n = 1639) depicted moderate-risk groups for CVD. Cluster 3 also had the highest degree of frailty and lung disease while Cluster 4 (n = 2233) represented a high-risk cohort for CVD. After adjusting for confounders, with cluster 1 as the reference, cluster 3 had the highest risk of all-cause death, HR 1.24 (1.09–1.41), ARD (10.3%), cardiovascular death, HR 1.56 (1.19–2.06), ARD (3.3%), non-cardiovascular death, HR 1.20 (1.04–1.38), ARD (6.9%), hospitalization for HF, HR 2.07 (1.71–2.50), ARD (9.1%) and VT/VF/CA, HR 1.74 (1.20–2.53), (ARD 1.3%). Conclusions: Four distinct clusters of AF patients were identified, discriminated by the differential presence of comorbidities. Our findings suggest that hospitalized AF patients with moderate CVD risk may have a poorer prognosis compared to hospitalized AF patients with high CVD risk in the presence of lung pathology and frailty. This subgroup of patients may require more stringent management of existing comorbidities such as chronic obstructive pulmonary disease and sleep apnea, alongside their AF.

Aims: Patients with heart failure (HF) are at increased risk of developing dementia, an outcome that substantially worsens clinical prognosis and quality of life. Sodium–glucose co-transporter 2 inhibitors (SGLT2i) are well-established in cardiovascular protection, but their association with incident dementia remains poorly documented, particularly in non-diabetic populations. Methods: We conducted a retrospective cohort study using the TriNetX Research Network (2016–2025), including adults with HF and no prior history of dementia or diabetes. Patients initiating SGLT2i (n = 46 049) were compared with non-users (n = 205 010). After 1:1 propensity score matching, 39 979 pairs were analysed. The primary outcome was new-onset dementia. Secondary outcomes were Alzheimer’s disease, vascular dementia, and all-cause mortality. Additional cardiovascular outcomes included ischaemic stroke, myocardial infarction, and end-stage kidney disease (ESKD). Outcomes were assessed using Kaplan–Meier survival analysis and Cox proportional hazards models. Results: Over a relatively short median follow-up of 1.2 years in a population with a mean age of 64 years, SGLT2i use was associated with a significantly lower risk of new-onset dementia [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.68–0.87; P < .001]. Risks were also reduced for Alzheimer’s disease (HR 0.58, 95% CI 0.45–0.74; P < .001), vascular dementia (HR 0.41, 95% CI 0.27–0.62; P < .001), and all-cause mortality (HR 0.63, 95% CI 0.61–0.66; P < .001). SGLT2i therapy was further associated with lower risks of ischaemic stroke (HR 0.67, 95% CI 0.60–0.75; P < .001) and ESKD (HR 0.75, 95% CI 0.63–0.89; P = .001). Conclusion: In this large, real-world patient with HF without diabetes, SGLT2i therapy was associated with a significantly lower risk of new-onset dementia and all-cause mortality.