Key result
SGLT2i use linked to ~32% lower risk of major events in older HFpEF patients.
Why the study?
Phenotypic heterogeneity of HFpEF has been reported, but the effectiveness of SGLT2 inhibitors across specific phenotypes remains uncertain.
Does SGLT2i treatment reduce the composite of kidney disease progression, heart failure readmission, and all-cause mortality in hospitalised Japanese patients with HFpEF?
Cohort (n=3,588)
Yes
Does SGLT2i treatment reduce the composite of kidney disease progression, heart failure readmission, and all-cause mortality in hospitalised Japanese patients with HFpEF?
Hazard Ratio: 0.68 (95% CI 0.54–0.86)
Absolute Event Rate: 18.4% vs 25%
p-value: p=0.002
SGLT2i treatment is associated with improved clinical outcomes and preserved renal function in Japanese patients with HFpEF, particularly in older patients with a high prevalence of atrial fibrillation.
May support SGLT2i consideration in older HFpEF; extends phenotypic observations but remains hypothesis-generating.
Background Phenotypic heterogeneity of heart failure with preserved ejection fraction (HFpEF) has been reported, particularly among racial groups. While phenotype-specific treatment for HFpEF has attracted attention, the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in this context remains uncertain. Aims This study aimed to explore the phenotypic characteristics of HFpEF in Japanese patients and to evaluate the differential effects of SGLT2i treatment Methods In this multicentre study, a total of 3,588 hospitalised patients with HFpEF (median age, 76.3 years; 54.8% male) were categorised into three groups based on the phenotypes of HFpEF. Phenotype 1 was the youngest patient with a low burden of comorbidities. Phenotype 2 was the oldest patient with a high prevalence of atrial fibrillation. Phenotype 3 was mostly obese and diabetic with high burden of other co-morbidities. The primary outcome was a composite endpoint including kidney disease progression—defined as a decrease in estimated glomerular filtration rate (eGFR) to <10 ml/min/1.73 m², a sustained decline in eGFR of at least 40%, or end-stage kidney disease—along with heart failure readmission and all-cause mortality. Results HFpEF consisted of phenotype 1: 787/21.9%, phenotype 2: 2,323/64.7%, and phenotype 3: 478/13.4%. Over a median follow-up of 2 years, the primary outcome event occurred in 74 of 403 participants (18.4%) in the SGLT2i group and 796 of 3,185 participants (25.0%) in the non-SGLT2i group (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.54 to 0.86; P = 0.002) (Figure). SGLT2i treatment was associated with a reduced risk of the primary outcome in phenotype 2 (HR: 0.68; 95% CI: 0.49–0.93; P = 0.014). The non-SGLT2i group showed progression of renal dysfunction over time, while the SGLT2i group preserved renal function across all phenotypes at 2 years. Conclusions Three distinct HFpEF phenotypes were identified among Japanese patients. SGLT2i treatment could improve clinical outcomes in a phenotype characterized by older age. The renoprotective effect was consistently observed regardless of phenotype.
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Sezaki et al. (2025) conducted a cohort in Heart failure with preserved ejection fraction (HFpEF) (n=3,588). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) vs. non-SGLT2i was evaluated on Composite of kidney disease progression (eGFR <10 ml/min/1.73 m², sustained decline ≥40%, or end-stage kidney disease), heart failure readmission, and all-cause mortality (HR 0.68, 95% CI 0.54-0.86, p=0.002). SGLT2i treatment was associated with a lower risk of kidney disease progression, HF readmission, or mortality compared to non-SGLT2i (18.4% vs 25.0%; HR 0.68; 95% CI 0.54-0.86; P=0.002).
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