Sodium-glucose co-transporter 2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an updated systematic review and meta-analysis

Abstract

Objectives Heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) are associated with significant morbidity and mortality, as well as growing health and economic burden. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are very promising for the outcome improvement of patients with HFpEF or HFmrEF. The meta-analysis was performed to investigate the effects of SGLT2 inhibitors in HFpEF or HFmrEF, by pooling data from all clinically randomized controlled trials (RCTs) available to increase power to testify. Methods Studies were searched in electronic databases from inception to November, 2022. We performed a meta-analysis to estimate the effect of SGLT2 inhibitors on clinical endpoints in patients with HFpEF or HFmrEF, using trial-level data with consistent endpoint definitions. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Hazard ratio (HR) was pooled with 95% confidence interval (CI) for dichotomous data. This study was registered with INPLASY 2022110095. Results Six studies involving 15,989 participants were included into the final analysis. Pooled analyses revealed that SGLT2 inhibitors significantly reduced the composite of HF hospitalization or cardiovascular death [HR: 0.79 (0.72–0.85); I2 = 0%; P < 0.00001] and HF hospitalizations [HR: 0.74 (0.67–0.82); I2 = 0%; P < 0.00001]. This finding was seen in both HFmrEF trials [HR: 0.76 (0.67–0.87); I2 = 49%; P < 0.0001] and HFpEF subgroup studies [HR: 0.70 (0.53–0.93); I2 = 0%; P = 0.01]. The incidence of any serious adverse events [OR: 0.89 (0.83–0.96); I2 = 0%; P = 0.002] was significantly lower in the SGLT2 inhibitor arm. No significant differences were observed between the two groups with regard to cardiovascular death and all-cause death. Conclusions This meta-analysis of patients with heart failure of left ventricular ejection fraction (LVEF) > 40% showed that SGLT2 inhibitors significantly reduce the risk of the composite of cardiovascular death and hospitalization for heart failure, but not cardiovascular death and all-cause death. Nevertheless, given that SGLT2 inhibitors may reduce the risk of hospitalization for heart failure, they should be considered the fundamental treatment for all patients with HFpEF or HFmrEF.

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors for heart failure with mildly reduced or preserved ejection fraction: a systematic review and meta-analysis of randomized controlled trials

“…A recent meta-analysis reported similar findings to ours but it did not explore the benefit of SGLT2i in improving the quality of life of patients (30). Our study showed that SGLT2i significantly improve the quality of life based on KCCQ and MLHF questionnaires which is an important finding for patients who desire effective treatment options that can not only alleviate symptoms but also improve their overall well-being and day-today functioning.…”

Avanços no Tratamento de Insuficiência Cardíaca: Perspectivas e Terapêuticas Emergentes

“…O objetivo deste estudo é contribuir para uma melhor compreensão das opções terapêuticas disponíveis e a avaliação do desfecho geral dessas terapias na gestão da insuficiência cardíaca. Wang et al, (2022) conduziram uma revisão sistemática atualizada e meta-análise que se concentrou na avaliação da eficácia dos inibidores do cotransportador de sódio-glicose 2 (SGLT2) em uma população específica de pacientes: aqueles com insuficiência cardíaca e fração de ejeção levemente reduzida ou preservada. Este estudo representou uma contribuição significativa para a literatura, pois abordou uma área emergente no tratamento da insuficiência cardíaca, destacando a promessa terapêutica dos inibidores do SGLT2 nesse subgrupo de pacientes.…”

Guía mexicana de práctica clínica para el diagnóstico y el tratamiento de la insuficiencia cardiaca

“…Wang et al 97 en 2022 publicaron una RS que evaluó el impacto de los iSGLT-2 en pacientes con ICFEp y ICFEm. Los autores incluyeron 6 ECAs con 15,989 participantes.…”

“…Entre estos beneficios, la pérdida ponderal ha generado mucho interés por la importancia que tienen el sobrepeso y la obesidad en la fisiopatología de distintas enfermedades metabólicas y cardiovasculares. Una RS publicada recientemente por Wang et al 152 demostró que el tratamiento de pacientes con insuficiencia cardiaca con iSGLT-2 se asoció a una disminución ponderal significativa (DM -1.36 kg, IC95%: -1.68; -1.03) 152 .…”