Early Use of SGLT2 Inhibitors in Heart Failure With Preserved Ejection Fraction: Quantitative Analysis of Cardiac Biomarkers, Renal Function, and In-Hospital Mortality
Authors: Souza Neto Luiz Francisco de , Carvalho Camila Maria Bertão , Bezerra Laura Emilly de Moura , Saldanha Luciano Victor Vasconcelos , Brito Artur Freire , Fonseca Kerolaine Silva , Santini Fernando Paniago , Viana Dionéa Ferreira Ayres , Aguiar Hildo Santiago Reis de , Oliveira Amanda Pinheiro , Oliveira Mariana Mota Benevides de , Turmina Nelso Gabriel Lippo , Moutinho Luis Guilherme Rodrigues de Almeida , Lôbo Rebeca Carvalho Wanderley de Lima , Oliveira Layanna Pessoa Marçal de , Santos Raíssa Maria Silvestre , Méllo Aurélia Lorena Toscano de Medeiros Borges de , Loureiro Levy Alves Pinto , Cavalcanti Dulce Cerqueira Ferreira , Chaves Ana Clara Onofre Brito , Bomfim José Mateus da Silva , Areal Ellen Pereira , Rodrigues Maria Eduarda Morales , Porcionato Rodrigo , Nascimento Joseane Oliveira Braga , Lima Harley Davidson Rocha de , Pereira Giovana Mendelski 
Published: February 2025

Objective: This study aims to systematically and quantitatively evaluate the early use of SGLT2 inhibitors in patients with heart failure with preserved ejection fraction (HFpEF), focusing on the analysis of cardiac biomarkers, renal function, and in-hospital mortality.

Theoretical Framework: HFpEF is a complex clinical syndrome associated with high hospitalization rates and limited effective therapeutic options. Initially developed for the management of type 2 diabetes mellitus, SGLT2 inhibitors have demonstrated significant cardiorenal benefits, including reductions in biomarkers such as NT-proBNP, improved renal function, and decreased heart failure hospitalizations, independent of diabetes status. Recent studies, such as EMPEROR-Preserved and DAPA-HF, have consolidated the role of this therapeutic class in reducing hospitalizations, although the impacts on cardiovascular and overall mortality remain controversial.

Method: A systematic review was conducted using PubMed, Scopus, and Web of Science databases, covering studies published between 2012 and 2024. A total of 21 studies were included, analyzing the effects of SGLT2 inhibitors in HFpEF, with outcomes related to the reduction of cardiac biomarkers, renal function improvement, and hospitalizations. Inclusion criteria focused on studies with sample sizes greater than 50 patients and relevant quantitative data.

Results and Discussion: The findings indicate that SGLT2 inhibitors significantly reduce cardiac biomarkers such as NT-proBNP, associated with improvements in hemodynamic burden and myocardial remodeling. Renal protection, evidenced by preserved glomerular filtration rates and reduced albuminuria, underscores the cardiorenal role of these drugs. Additionally, a consistent reduction in heart failure hospitalizations was observed, with additional benefits in quality of life. However, the impact on cardiovascular and overall mortality remains controversial, varying across analyzed patient subgroups.

Research Implications: This study highlights the need for future research to explore specific subgroups of HFpEF patients, considering factors such as age, comorbidities, and ejection fraction profiles. Multicenter and long-term clinical trials are essential to elucidate the effects of SGLT2 inhibitors on mortality and to consolidate their incorporation into therapeutic guidelines.

Originality/Value: This systematic review provides robust evidence on the efficacy of SGLT2 inhibitors in the management of HFpEF patients, highlighting their benefits in reducing hospitalizations, improving renal function, and controlling cardiac biomarkers. The findings reinforce the relevance of this therapeutic class as a significant advancement in HFpEF treatment.