The Effect of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors on Mortality and Hospitalization in Patients with Heart Failure with Reduced Ejection Fraction: A Systematic Review and Meta-analysis

RESUMO

Atef Eid Madkour Elsayed*, Mohammed Abdulla AlShikh, Emad bani Alharbi, Lelyan Sami Alqurshi, mGhazi Awad A Al qahtani, Ehab Ali, Zaidah Moeteg AlQahtani, Hamad Abkar Hakami, Ahmed sami alqurashi, Saleh Taher Almubarak, Mohanad Atiah Alzahrani

Background: Heart failure with reduced ejection fraction (HFrEF) remains associated with high rates of hospitalization and mortality despite advances in guideline-directed therapy. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially developed for diabetes management, have emerged as a novel therapeutic option in heart failure.

Objectives: This systematic review and meta-analysis aimed to evaluate the impact of SGLT2 inhibitors on mortality, hospitalization, surrogate outcomes, and patient-reported health status in individuals with HFrEF.

Methods: A comprehensive search of PubMed, Scopus, Embase, Web of Science, and Cochrane CENTRAL was conducted (2015–2023). Eligible studies included randomized controlled trials and meta-analyses examining SGLT2 inhibitors in adults with HFrEF. Ten clinical trials and multiple systematic reviews were included. Outcomes assessed were all-cause and cardiovascular mortality, hospitalization for heart failure, biomarkers (e.g., NT-proBNP), cardiac remodeling, and quality of life (Kansas City Cardiomyopathy Questionnaire, KCCQ).

Results: Large-scale trials, including DAPA-HF and EMPA-REG OUTCOME, demonstrated significant reductions in the composite endpoint of cardiovascular death or heart failure hospitalization, with risk reductions of 25– 38%. Mechanistic studies showed mixed effects on biomarkers, but consistent improvements in left ventricular remodeling and NT-proBNP in select populations. Patient-reported outcomes improved across multiple trials, with dapagliflozin and canagliflozin associated with meaningful increases in KCCQ scores. Safety analyses confirmed favourable tolerability across diabetic, non-diabetic, older, and frail populations.

Conclusions: SGLT2 inhibitors consistently reduce mortality and hospitalization in patients with HFrEF while improving symptoms and quality of life. Their efficacy across diabetic and non-diabetic populations, together with a strong safety profile, supports their role as cornerstone therapy in HFrEF.