Excerpts From SGLT2 [Empagliflozin] For HFpEF From The Curbsiders’ Episode #307

In this post, I link to The Curbsiders‘ [Link is to the Full Episode List] podcast and show notes, #307 Spooky Tofurkey Cakes: SGLT2 for HFpEF, Diverticulitis, VTE update, Rotator Cuff Disease.

*Please see Empagliflozin in Heart Failure with a Preserved Ejection Fraction [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. N Engl J Med. 2021 Oct 14;385(16):1451-1461

And all that  follows are excerpts from “SGLT2 for HFpEF [about the EMPEROR-Preserved Trial] show notes. 11:52 –


Anker et al. EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. The New England Journal of Medicine. 2021; 385:1451-1461.  DOI: 10.1056/NEJMoa2107038. 

Question: Do SGLT2 inhibitors decrease mortality or the risk of hospitalization in patients with Heart Failure with Preserved Ejection Fraction (HFpEF)?

Comparison:  Empagliflozin 10 mg once daily was compared with placebo, in addition to usual therapy, in this double-blind, randomized superiority trial that tracked outcomes for a median 26.2 months in patients with LVEF of at least 40%, an elevated BNP, and class II-IV heart failure symptoms.

Results:  This trial was a positive trial. 

The primary outcome occurred in 13.8% in the empagliflozin group vs 17.1% in the placebo group (HR 0.79, CI 0.69-0.90, p < 0.001). Notably, the difference was primarily driven by a lower risk of hospitalization for heart failure in the empagliflozin group. Consistent with EMPEROR-Reduced (Packer, 2020), a difference was not seen between groups for all-cause or cardiovascular mortality.

Listeners should realize that nearly 20% of patients in the empagliflozin and placebo group stopped the study medication. Various adverse events were common (approximately 86% in both groups) with hypotension, urinary tract infections, and genital infections more common in the empagliflozin group (see Supplement Table S6).

Bottom Line: Empagliflozin reduced combined risk of CV death or hospitalization for heart failure in pts with HFpEF, with or without diabetes. This effect was primarily in decreasing hospitalizations, and additionally, a reduced rate of renal function decline was noted in the empagliflozin cohort. This is one of the first drugs to show benefit in HFpEF. Notably, patients with moderately reduced EF seemed to derive the greatest benefit.

Hotcakes rating: 4.5

Additional Reading: 

  1. EMPEROR-Preserved summary by Kumbhani DJ, American College of Cardiology 
  2. EMPEROR-Preserved summary, Wiki Journal Club
  3. The DELIVER Trial is ongoing with Dapagliflozin for HFpEF
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