Association of Eligibility for a Sodium-Glucose Cotransporter 2 Inhibitor and Cardiovascular Events in Patients With Atrial Fibrillation

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce heart failure (HF) in a broad range of populations, but they have not been studied specifically in patients with atrial fibrillation (AF). We aimed to examine the association between SGLT2i eligibility and cardiovascular events in patients with AF to evaluate the potential utility of SGLT2is for AF management. METHODS: We pooled data from 2 randomized controlled trials (RCTs) of patients with AF (RE-LY and ACTIVE-W). Among patients assigned to anticoagulation arms, those meeting the enrollment criteria from at least 1 of the phase 3 SGLT2i RCTs were classified as "SGLT2i eligible" and the remainder as "SGLT2i ineligible." The primary outcome was the composite of HF hospitalization or cardiovascular death. RESULTS: A total of 21,484 patients with AF (mean age: 71.2 ± 8.8, 36.1% women, median CHA₂DS₂-VASc Score = 3) were included. The proportion of patients with AF eligible for SGLT2i was 41.2%. SGLT2i-eligible patients had higher rates of cardiovascular death or hospitalization for HF (5.8 vs 3.2 per 100 person-years, P_log-rank < 0.001), cardiovascular death (3.9 vs 1.5 per 100 person-years, P_log-rank < 0.001), and hospitalization for HF (2.5 vs 1.9 per 100 person-years, P_log-rank < 0.001). The age- and sex-adjusted model showed that SGLT2i-eligible patients were at a higher risk of cardiovascular death and hospitalization for HF (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.79-2.17; P < 0.001), cardiovascular death (HR, 2.75; 95% CI, 2.41-3.13; P < 0.001), and hospitalization for HF (HR, 1.41; 95% CI, 1.23-1.62; P < 0.001) than ineligible patients. CONCLUSIONS: Most patients with AF do not currently have indications for SGLT2is but still have substantial risk of cardiovascular events. Future randomized trials should evaluate the efficacy of SGLT2is in patients with AF.