Tailoring medical therapy for heart failure with preserved ejection fraction

Introduction

Heart failure with preserved ejection fraction (HFpEF) accounts for half of the hospitalization for heart failure (HF) worldwide, and the prevalence is expected to increase along with population aging and increasing burden of cardio-kidney-metabolic disorders.¹ Treatment options for chronic HFpEF have expanded in recent years.² Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are now guideline-recommended as a first-line treatment in patients with mildly reduced and preserved ejection fraction. In a meta-analysis of the EMPEROR-Preserved and DELIVER trials, SGLT2i reduced cardiovascular (CV) death or first hospitalization for HF by 20% with consistent reductions in both components (12% risk reduction in CV death and 26% risk reduction in first hospitalization for HF), among HF patients with left ventricular ejection fraction (LVEF) >40%.³ In the PARAGON-HF trial, treatment with sacubitril/valsartan led to a marginal reduction of total hospitalizations for HF and CV death compared to valsartan in patients with HF and LVEF ≥45%, with a more pronounced benefit observed in those with an LVEF below normal.⁴ Based on the results of this trial, sacubitril/valsartan received indications for use in patients with HF with mildly reduced ejection fraction (HFmrEF) and selected patients with HFpEF with an LVEF below normal in the United States. Lastly, in the FINEARTS-HF trial, the non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone showed a 16% relative risk reduction of worsening HF events and death from CV causes compared to placebo among patients with HF and LVEF ≥40%.⁵

These advances in HFpEF pharmacotherapy, along with the substantial residual risk of this population, highlight the need for an accelerated optimization of foundational medical therapy.