SGLT2i reduces composite of CV death or HF hospitalization in HF patients with LVEF ≥50%

EMPEROR-Preserved: Empagliflozin in Heart Failure with a Preserved Ejection Fraction ≥50% - Results from the EMPEROR-Preserved Clinical Trial

Presented at the American Heart Association’s Scientific Sessions 2021 by: Prof. Stefan Anker MD, PhD - Berlin, Germany

Introduction and methods

Aim of the study

The results of EMPEROR-Preserved trial were presented at the ESC 2021 conference earlier this year and showed that empagliflozin significantly reduced the risk of the primary composite endpoint of time to first event of CV death or HF hospitalization, compared to placebo, in patients with HF and LVEF >40%, with and without T2DM. This analysis of the EMPEROR-Preserved trail assessed the effects of empagliflozin in HF patients with preserved LVEF of ≥50% (HFpEF) and in HF patients with mildly reduced LVEF of 41-49% (HFmrEF).

Study design

EMPEROR-Preserved randomized a total of 5988 patients with HF (aged ≥18 years, LVEF >40%, NYHA class II-IV, elevated NT-proBNP, eGFR ≥20, T2DM and non-T2DM) to receive either empagliflozin 10 mg once daily + standard of care (n=2997), or placebo + standard of care (n=2991)). Randomization was stratified by baseline LVEF ≥50% vs. 41-49%. 4005 patients had HFpEF and 1983 had HFmrEF. The median follow-up was 26 months.

Primary outcome

The composite primary endpoint was time to first event of CV death or HF hospitalization. Other reported outcomes were first and total HF hospitalizations, CV death, all-cause mortality, slope of decline in eGFR over time and improvement in quality of life as measured by KCCQ CSS.

Main results

• In patients with LVEF ≥50%, empagliflozin reduced the primary endpoint of time to first event of CV death or HF hospitalization by 17%, compared to placebo (HR 0.83, 95% CI 0.71-0.98, P=0.024). This was result was driven by a significant reduction in first HF hospitalizations (HR 0.78, 95% CI 0.64-0.95, P=0.013). There were no significant differences in CV death, all-cause mortality and total HF hospitalizations between the two treatment groups in patients with LVEF ≥50%.
• In patients with LVEF 41-49%, empagliflozin significantly reduced the primary endpoint by 29% (HR 0.71, 95% CI 0.57-0.88, P=0.002), first HF hospitalizations by 42% (HR 0.58, 95%CI 0.44-0.77, P<0.001) and total HF hospitalizations by 43% (HR 0.57, 95% CI 0.42-0.79, P<0.001), compared to placebo. There were no significant differences between the empagliflozin and placebo groups for CV death and all-cause mortality.
• Quality of life as measured by KCCQ-CSS was similarly improved by empagliflozin in patients with LVEF ≥50% and LVEF 41-49% (adjusted mean difference of empagliflozin vs. placebo for mean change in KCCQ-CSS from baseline: 1.46, 95%CI 0.42-2.51, P=0.006; and 1.56, 95%CI 0.05-3.06, P=0.043; respectively. P value for interaction = 0.92).
• Empagliflozin also reduced the slope of decline in eGFR from baseline in patients with LVEF ≥50%. The difference compared to placebo in slope of decline in eGFR over time was 1.24 mL/min/1.73 m² per year (P<0.0001).

Conclusion

This analysis of the EMPEROR-Preserved trial showed that empagliflozin significantly reduced the primary endpoint of time to first event of CV death or HF hospitalization by 17% in HFpEF patients with LVEF ≥50% and by 29% in HFmrEF patients with LVEF 41-49%. This benefit was driven by significant reductions in first HF hospitalizations. Treatment with empagliflozin was also associated with significant improvements in quality of life.

-Our reporting is based on the information provided at the American Heart Association’s Scientific Sessions 2021-