EMPEROR-Preserved: Diastolic dysfunction might predict response to empagliflozin

Diastolic dysfunction at baseline was associated with an improved response to empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF) who were enrolled in the EMPEROR-Preserved trial. The authors reasoned that this may imply that empagliflozin targets specific changes in diastolic performance.

The EMPEROR-Preserved trial (NCT03057951) randomised 5,988 patients with HF and a left ventricular ejection fraction (LVEF) >40% 1:1 to empagliflozin or placebo, added to standard-of-care, and the primary analysis delivered positive results [1]. Now, Dr Andrew Stewart Coats (Heart Research Institute, Australia) and colleagues looked at the interaction effect between diastolic dysfunction and treatment on the primary endpoint of cardiovascular death or hospitalisation for HF [2]. Diastolic dysfunction was defined as the presence of a left atrial volume index ≥34 mL/m², an E/e’ ratio ≥13, or a LV mass index >115 g/m² for men or >95 g/m² for women. Participants were stratified according to the number of features of diastolic dysfunction they had at baseline, either 0 (n=3,766), 1 (n=1,619), or ≥2 (n=603).

The analysis showed that there was a significant interaction effect between diastolic dysfunction at baseline and the treatment effect of empagliflozin on the primary endpoint of cardiovascular death or hospitalisation for HF. The corresponding hazard ratios were 0.91 for participants without diastolic dysfunction at baseline, 0.64 for participants with 1 feature of diastolic dysfunction at baseline, and 0.49 for those who had 2 or more features of diastolic dysfunction (P_interaction=0.0014). No differences were observed between the 3 strata concerning safety outcomes.

Baseline diastolic dysfunction predicted the clinical response to empagliflozin among patients with HFpEF in the EMPEROR-Preserved trial. “This may indicate that the mode-of-action of empagliflozin is directed against certain characteristics of diastolic performance,” expressed Dr Coats.

1. Anker SD, et al. N Engl J Med 2021;385:1451-1461.
2. Stewart Coats AJ, et al. EMPEROR-Preserved: association of echocardiographic features of diastolic dysfunction with the clinical efficacy of empagliflozin in HFpEF. Clinical trials updates in medical therapy, Heart Failure 2025, 17–20 May, Belgrade, Serbia.

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Posted on 17 July 202521 July 2025