Packer M, Anker SD, Butler J, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190.
Abstract

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes. More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction.

METHODS: In this double-blind trial, we randomly assigned 3730 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure.

RESULTS: During a median of 16 months, a primary outcome event occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio for cardiovascular death or hospitalization for heart failure, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P<0.001). The effect of empagliflozin on the primary outcome was consistent in patients regardless of the presence or absence of diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.70; 95% CI, 0.58 to 0.85; P<0.001). The annual rate of decline in the estimated glomerular filtration rate was slower in the empagliflozin group than in the placebo group (-0.55 vs. -2.28 ml per minute per 1.73 m2 of body-surface area per year, P<0.001), and empagliflozin-treated patients had a lower risk of serious renal outcomes. Uncomplicated genital tract infection was reported more frequently with empagliflozin.

CONCLUSIONS: Among patients receiving recommended therapy for heart failure, those in the empagliflozin group had a lower risk of cardiovascular death or hospitalization for heart failure than those in the placebo group, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Reduced ClinicalTrials.gov number, NCT03057977.).

Ratings by Clinicians (at least 3 per Specialty)
Specialty Score
Cardiology
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Internal Medicine
Nephrology
Comments from MORE raters

General Internal Medicine-Primary Care(US) rater

This important, well-designed study confirms the benefit of empagliflozin in patients with CHF, with or without DM.

Internal Medicine rater

Cardiologists are beginning to prescribe these drugs in the absence of diabetes.

Internal Medicine rater

It looks like the main effect is the diuretic effect on symptoms. There is really not much of a signal for improved mortality. I wish there was greater clarity about renal outcomes other than estimated GFR (which might be an artefact of this class of drugs). What about separating out dialysis and transplant? Can you ask the authors for this?

Nephrology rater

One more addition to the ever improving therapy for congestive heart failure. With more and more people expected to be diagnosed with CHF in coming decades, this is good news for physicians and their patients.

Nephrology rater

This is consistent with the previous, growing, impressive SLGT2i literature.