Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure With Supra-Normal Ejection Fraction: A Target...

The efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in heart failure (HF) with preserved ejection fraction has been established. However, their benefits in patients with HF with supra-normal ejection fraction (HFsnEF) remain unclear. We aimed to investigate the efficacy of SGLT2i therapy in patients with HFsnEF (left ventricular ejection fraction ≥65%). We conducted a single-center target trial emulation using observational data within an intention-to-treat framework. Eligible participants were adults aged ≥40 years with chronic HF who were not receiving SGLT2i at baseline and had evidence of structural heart disease and elevated natriuretic peptide levels. Patients who received SGLT2i were classified into the SGLT2i (+) group, whereas those who did not receive SGLT2i were classified into the SGLT2i (-) group. The primary outcome was a composite of cardiovascular death and HF hospitalization. Inverse probability of treatment weighting was used to adjust for confounders. During a median follow-up of 374 days (interquartile range: 156 to 747 days), the primary composite outcome occurred in 55 and 263 patients in the SGLT2i (+) and SGLT2i (-) groups, respectively. The weighted Cox hazard ratio for the composite outcome was 0.63 (95% confidence interval [CI]: 0.45 to 0.88, p = 0.007). For individual outcomes, the hazard ratio was 0.76 for cardiovascular death (95% CI: 0.33 to 1.72, p = 0.508), and 0.68 (95% CI: 0.48 to 0.96, p = 0.026) for HF hospitalization. SGLT2i use was associated with a significant reduction in the composite risk of cardiovascular death or HF hospitalization in patients with HFsnEF.