Sodium–Glucose Cotransporter 2 Inhibitors in Heart Failure with Preserved Ejection Fraction: Rationale for and Practical Use of a Successful Therapy

Abstract

Heart failure (HF) with preserved left ventricular ejection fraction is a common disease with a poor prognosis and rising prevalence in the community. The current paradigm of treatment includes symptomatic therapy, such as diuretics, and risk factor control and treatment of comorbidities. According to European guidelines, there is no effective therapy for patients with HF with left ventricular ejection fraction (LVEF) ≥50%, while drugs normally used in HF with reduced LVEF might also be effective for patients with mildly reduced LVEF (40–50%), with a IIB class of recommendation. The recently published EMPEROR-Preserved trial has challenged current guidelines, demonstrating improved outcomes in patients with HF and LVEF >40% with the sodium–glucose cotransporter 2 inhibitor (SGLT2I) empagliflozin, compared with placebo. This result was consistent in patients with and without diabetes as well as in those with LVEF below and above 50%. The authors describe the rationale for this therapy, presenting the main results of the EMPEROR-Preserved trial, and provide some recommendations for the everyday clinical management of HF with preserved left ventricular ejection with an SGLT2I.

The Therapy and Management of Heart Failure with Preserved Ejection Fraction: New Insights on Treatment

“…The introduction of SGLT2i has transformed the paradigm of HFpEF treatment. 46,47 Rather than solely targeting neurohormonal activation, this class of drugs addresses comorbidities, which is a peculiar feature of HFpEF, and offers a valuable opportunity for cross-sectional intervention on the cardio-renal-metabolic continuum, which is profoundly altered in these patients.…”

Biomarkers of HFpEF: Natriuretic Peptides, High-Sensitivity Troponins and Beyond

“…However, the recent EMPEROR-Preserved (EMPagliflozin outcome trial in Patients With chronic heart Failure With Preserved Ejection Fraction) trial has demonstrated improved outcomes in patients with HF and LVEF > 40% with the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin as compared to the placebo. There was no signal of a differential effect in the subgroups with or without diabetes as well as in patients with LVEF below and above 50% [ 13 , 14 ]. The results of the DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With Preserved Ejection Fraction Heart Failure) trial (NCT03619213), a phase III trial enrolling HFpEF and HFmrEF patients and testing dapagliflozin versus placebo, are expected in the near future [ 15 ].…”