Empagliflozin efficacious in HF patients with preserved ejection fractions ≥50%

The EMPEROR-Preserved is the first large-scale trial that showed meaningful improvements of a drug therapy in patients with preserved ejection fraction. In a subanalysis of the trial, empagliflozin also demonstrated clinical benefits for heart failure (HF) in patients with left ventricular ejection fraction (LVEF) ≥50%. This result extended to health-related quality of life and symptoms.

EMPEROR-Preserved (NCT03057951) evaluated the efficacy and safety of the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin compared with placebo in patients with HF with preserved ejection fraction (HFpEF) [1,2]. The trial included 5,988 patients with an LVEF >40%. Dr Stefan Anker (Charité University Berlin, Germany) presented the current analysis, which assessed the subset of included patients with truly preserved EF (≥50%) (n=4,005), in line with the recently updated ESC Guidelines on HF [3]. This analysis is relevant for trial comparisons and guideline recommendations. The primary outcome was a composite score of time to cardiovascular death or HF hospitalisation.

At 52 weeks, the primary endpoint of empagliflozin was met for patients with LVEF ≥50% (HR 0.83; P=0.024). The effect was driven by first HF hospitalisation (HR 0.78; P=0.013). No significant effect of empagliflozin was found on cardiovascular death, all-cause mortality, or cumulative HF hospitalisation (see Figure). The effect of empagliflozin on the primary endpoint in patients with an LVEF between 41% and 49% was numerically more pronounced (HR 0.71; P=0.002). Nonetheless, no interaction effect was observed between patients with LVEF ≥50% and patients with an LVEF ranging from 41% to 49% (P=0.27) regarding the primary outcome. A trend analysis did not reveal a significant trend of the effect of empagliflozin across 5% LVEF margins (50–55%, 55–60%, and so on up to >70%). The Kansas City Cardiomyopathy Questionnaire (KCCQ) demonstrated quality-of-life benefits of empagliflozin for patients with LVEF ≥50% (adjusted mean difference 4.24) compared with placebo (adjusted mean difference 2.78). Finally, empagliflozin receivers showed a significant and ongoing improvement on the New York Heart Association (NYHA) functional class score.

Figure: Primary and secondary outcomes for LVEF ≥50% [1]



CI, confidence interval; CV, cardiovascular; HHF, hospitalisation for heart failure; HR, hazard ratio; LVEF, left ventricular ejection fraction.

Dr Anker highlighted that the 17% reduction on the primary clinical endpoint in this study is remarkable compared with other pharmaceutical interventions for patients with HFpEF assessed in previous clinical trials. “Prior clinical trials showed efficacy rates between 4–8%. Thus, empagliflozin is the first agent to demonstrate a meaningful effect in HF patients with truly preserved EF in a large-scale trial.”

 

1. 
   
   1. Anker SD, et al. Empagliflozin in Heart Failure With a Preserved Ejection Fraction ≥50% – Results From the EMPEROR-Preserved Clinical Trial. LBS05, AHA Scientific Sessions 2021, 13–15 November.
   2. Anker SD, et al. N Engl J Med 2021;385:1451–1461.
   3. McDonagh TA, et al. Eur Heart J 2021;42(36):3599–3726.

 

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Posted on 14 January 202222 February 2024