Impact of Functional Frailty Measured by Short Physical Performance Battery Test on the Effectiveness of SGLT2 Inhibitors in Elderly Patients with Acute Heart Failure:PROFUND-IC Registry
7 affiliations
- 1Department of Internal Medicine, Hospital Clínico San Carlos, 28040 Madrid, Spain
- 2Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
- 3Health Research Institute, Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
- 4Research Methodological Support Unit and Preventive Department, Hospital Clínico San Carlos, 28040 Madrid, Spain
- 5Department of Internal Medicine, Complejo Asistencial de Ávila, 05071 Ávila, Spain
- 6Department of Internal Medicine, Hospital 12 de Octubre, 28041 Madrid, Spain
- 7Department of Internal Medicine, Hôpitaux Universitaires de Strasbourg, 67200 Strasbourg, France
Abstract
Background/Objectives: Acute heart failure (AHF) is the leading cause of hospitalization among patients over 65 years and is frequently associated with frailty. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) currently represent the only drug class recommended across the entire ejection fraction spectrum, although evidence regarding their effectiveness according to frailty status remains limited. Aims: To determine whether functional frailty, measured by the Short Physical Performance Battery (SPPB) test, influences the effectiveness of SGLT2i in reducing hospital readmission and mortality in elderly patients with AHF. Methods: Observational study of 794 polypathological patients admitted to Internal Medicine with AHF. An interaction analysis assessed whether SPPB, as a continuous variable, modified the association between SGLT2i and the composite outcome (hospital readmission or death), using a Cox model. The sample was further divided by SPPB test score (below 4 (N = 477) or ≥4 (N = 317)) for exploratory analyses. Descriptive and comparative analyses were performed according to SGLT2i administration, using the chi-squared test for qualitative variables and Student’s t-test for quantitative ones (Fisher’s and Mann–Whitney U test as appropriate). Survival analysis was done using Kaplan–Meier curves and Cox regression, with multivariable adjustment for confounders. Results: No significant interaction was found between SPPB score and SGLT2i (p = 0.506). When SPPB was dichotomised, SGLT2i treatment was associated with significantly lower all-cause mortality (3.7% vs. 12.0%; p = 0.018) and readmission (30.3% vs. 45.2%; p = 0.021) in SPPB ≥ 4, with mortality and readmission also numerically lower, without reaching statistical significance, in SPPB < 4 (mortality 12.9% vs. 16.9%, p = 0.410; readmission 34.5% vs. 42.0%, p = 0.220). After adjustment, SGLT2i treatment in the SPPB ≥ 4 group remained associated with a numerically lower hazard for the composite outcome (HR 0.652; 95% CI 0.418–1.018; p = 0.060). Conclusions: No evidence was found that functional frailty modifies the effectiveness of SGLT2i in elderly polypathological patients with AHF. An exploratory analysis suggested a possible gradient of greater association with SPPB ≥ 4, although this should be interpreted as hypothesis-generating.
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BibTeX
@article{guzmancarreras2026impact,
title = {{Impact of Functional Frailty Measured by Short Physical Performance Battery Test on the Effectiveness of SGLT2 Inhibitors in Elderly Patients with Acute Heart Failure:PROFUND-IC Registry}},
author = {Alicia Guzmán-Carreras and Purificación Romero-Jiménez and Sahar Okab and Rafael Sánchez-del Hoyo and Aladin Abdelhady Kishta-Kishta and Juan Igor Molina-Puente and Fernando Aguilar-Rodríguez and Noel Lorenzo-Villalba and Emmanuel Andrès and María del Rosario Iguarán-Bermúdez and Manuel Méndez-Bailón},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15207769},
url = {https://www.mdpi.com/2077-0383/15/20/7769},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Impact of Functional Frailty Measured by Short Physical Performance Battery Test on the Effectiveness of SGLT2 Inhibitors in Elderly Patients with Acute Heart Failure:PROFUND-IC Registry
AU - Alicia Guzmán-Carreras
AU - Purificación Romero-Jiménez
AU - Sahar Okab
AU - Rafael Sánchez-del Hoyo
AU - Aladin Abdelhady Kishta-Kishta
AU - Juan Igor Molina-Puente
AU - Fernando Aguilar-Rodríguez
AU - Noel Lorenzo-Villalba
AU - Emmanuel Andrès
AU - María del Rosario Iguarán-Bermúdez
AU - Manuel Méndez-Bailón
PY - 2026
DA - 2026/10/01
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15207769
UR - https://www.mdpi.com/2077-0383/15/20/7769
AB - Background/Objectives: Acute heart failure (AHF) is the leading cause of hospitalization among patients over 65 years and is frequently associated with frailty. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) currently represent the only drug class recommended across the entire ejection fraction spectrum, although evidence regarding their effectiveness according to frailty status remains limited. Aims: To determine whether functional frailty, measured by the Short Physical Performance Battery (SPPB) test, influences the effectiveness of SGLT2i in reducing hospital readmission and mortality in elderly patients with AHF. Methods: Observational study of 794 polypathological patients admitted to Internal Medicine with AHF. An interaction analysis assessed whether SPPB, as a continuous variable, modified the association between SGLT2i and the composite outcome (hospital readmission or death), using a Cox model. The sample was further divided by SPPB test score (below 4 (N = 477) or ≥4 (N = 317)) for exploratory analyses. Descriptive and comparative analyses were performed according to SGLT2i administration, using the chi-squared test for qualitative variables and Student’s t-test for quantitative ones (Fisher’s and Mann–Whitney U test as appropriate). Survival analysis was done using Kaplan–Meier curves and Cox regression, with multivariable adjustment for confounders. Results: No significant interaction was found between SPPB score and SGLT2i (p = 0.506). When SPPB was dichotomised, SGLT2i treatment was associated with significantly lower all-cause mortality (3.7% vs. 12.0%; p = 0.018) and readmission (30.3% vs. 45.2%; p = 0.021) in SPPB ≥ 4, with mortality and readmission also numerically lower, without reaching statistical significance, in SPPB < 4 (mortality 12.9% vs. 16.9%, p = 0.410; readmission 34.5% vs. 42.0%, p = 0.220). After adjustment, SGLT2i treatment in the SPPB ≥ 4 group remained associated with a numerically lower hazard for the composite outcome (HR 0.652; 95% CI 0.418–1.018; p = 0.060). Conclusions: No evidence was found that functional frailty modifies the effectiveness of SGLT2i in elderly polypathological patients with AHF. An exploratory analysis suggested a possible gradient of greater association with SPPB ≥ 4, although this should be interpreted as hypothesis-generating.
SN - 2077-0383
ER -