Association of SGLT2 Inhibitor Use With Outcomes in Patients With Frailty Hospitalized for Acute Heart Failure: Insights From a Multicenter Japanese Registry

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Abstract
Background: SGLT2 (sodium–glucose cotransporter‐2) inhibitors (SGLT2is) improve outcomes in heart failure (HF), but evidence in patients with frailty and acute HF (AHF) is limited. This study investigated the association between SGLT2i use at discharge and outcomes in patients with AHF, with a focus on frailty. Methods: We analyzed 5579 patients hospitalized for AHF enrolled between 2018 and 2024 in the prospective WET‐HF2 (West Tokyo Heart Failure 2) registry in Japan (age 79 years, 43% women, body mass index 23.1, 23% ischemic cause, left ventricular ejection fraction 45%, 24% SGLT2is at discharge). Frailty was assessed using the Clinical Frailty Scale (≥4; 63%), and complementary analyses were performed using frailty‐related factors (low body mass index, reduced activities of daily living, malnutrition, and dementia). The primary outcome was a composite of cardiac death or HF rehospitalization within 1 year, which occurred in 766 patients (18%). A propensity score was calculated using variables associated with SGLT2i prescription. Results: After propensity score–based inverse probability of treatment weighting adjustment, SGLT2i use was associated with a lower risk of the primary outcome (hazard ratio [HR], 0.76, P =0.045). This association was more pronounced in patients with frailty (HR, 0.59, P =0.005), but not in patients without frailty (HR, 1.18; P interaction =0.010). Analyses using frailty‐related factors yielded similar patterns. At 1 year, SGLT2i use at discharge was not associated with deterioration in body mass index or nutritional status. Conclusions: In this observational registry, SGLT2i use at discharge was associated with improved outcomes in patients with AHF, particularly those with frailty, without evidence of nutritional harm. These findings support the potential safety of SGLT2is in patients with frailty and AHF.

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