Background In EMPEROR-Preserved, empagliflozin reduced the composite primary endpoint of cardiovascular (CV) death/hospitalisation for heart failure (HHF) in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) >40%. We assessed the effect of empagliflozin in patients with a preserved LVEF ≥50% (considered ‘true HFpEF’ by many clinicians) and contrasted it with HF patients with mildly-reduced LVEF of 41–49% (i.e., <50%).

Methods Of 5,988 randomised patients, 1,983 had LVEF <50% and 4,005 had LVEF ≥50%. The outcomes included (1) the primary endpoint, (2) first and total HHF, (3) change in KCCQ-Clinical Summary Score (CSS), and (4) NYHA class at Week 52.

Results Patients with LVEF ≥50% (vs LVEF <50%) were more frequently women and were older; they had median NT-proBNP 946 pg/mL, and mean eGFR 59 mL/min; approximately half had atrial fibrillation or diabetes at baseline. In patients with LVEF ≥50%, empagliflozin reduced the risk of CV death/HHF by 17% (p=0.024), driven by a reduction in HHF (see table). Time-to-first-event of HHF was reduced by 22% (p=0.013) and total HHF by 17% (p=0.113). Empagliflozin produced meaningful improvements in KCCQ-CSS and NYHA class at Week 52. Compared with placebo, empagliflozin increased KCCQ-CSS in patients with LVEF ≥50% by 1.46 points (0.42–2.51; p=0.006); these empagliflozin-treated patients were 34% more likely to be in a lower NYHA class (p<0.001).

Conclusion In EMPEROR-Preserved, empagliflozin significantly improved CV death/HHF in patients with LVEF ≥50% by 17%, driven by reductions in HHF. This is the first large-scale study documenting event reductions and quality-of-life benefits in patients with true HFpEF.

Conflict of Interest Received consultancy fees/lecture honoraria/research funding from the following: Boehringer Ingelheim, Eli Lilly, AstraZeneca, Novartis, BMS, Servier, Medtronic, and Novo Nordisc.