Frailty index and tolerability of SGLT2 inhibitors in elderly (≥75 years) patients with heart failure

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are cornerstone therapies for heart failure (HF), but data on tolerability in frail elderly patients (≥75 years) remain limited. This study investigates the relationship between frailty status and SGLT2i tolerability in elderly HF patients and its impact on short-term clinical outcomes. We retrospectively enrolled 115 patients aged ≥75 years with HF who received SGLT2i between February 2023 and February 2024. Patients were stratified by Fried frailty phenotype score into a non-frail group (score < 3, n = 64) and a frail group (score ≥ 3, n = 51). The primary outcome was a 6-month composite of SGLT2i intolerance (permanent discontinuation, dose reduction, or interruption ≥ 7 days). Secondary outcomes included early intolerance (≤30 days), adverse events, and clinical outcomes. Between-group comparisons were performed using the t test, Mann–Whitney U test, or χ 2 test as appropriate. Multivariable logistic regression was used to assess the association between frailty and intolerance, with results presented as adjusted odds ratios (OR) with 95% confidence intervals (CI). Cox regression was applied for time-to-event outcomes, reported as hazard ratios (HR) with 95% CI. Over 6 months, 32 patients (27.8%) experienced SGLT2i intolerance. The frail group had a significantly higher intolerance rate than the non-frail group (39.2% vs 18.8%; adjusted OR = 2.31, 95% CI: 1.06–5.04, P = .035). Early intolerance (≤30 days) was also more frequent in frail patients (23.5% vs 9.4%; adjusted OR = 2.89, 95% CI: 1.08–7.76, P = .034). Adverse events such as symptomatic hypotension/volume depletion, AKI, and infections were more common in frail patients. Clinical outcomes including HF-related rehospitalization (29.4% vs 15.6%), all-cause rehospitalization (37.3% vs 21.9%), and all-cause mortality (17.6% vs 7.8%) were higher in frail patients, though differences were not statistically significant. The association between frailty and intolerance was more pronounced in patients with eGFR < 45 mL/min/1.73m 2 (interaction P = .041). In elderly (≥75 years) HF patients, frailty is significantly associated with increased SGLT2i intolerance, particularly in those with reduced renal function, highlighting the need for individualized treatment strategies.