EMPEROR-Reduced boosts case for SGLT2 inhibition in HF irrespective of diabetes
medwireNews: The EMPEROR-Reduced investigators have revealed that empagliflozin provides significant protection against cardiovascular death and heart failure (HF) in patients with HF and reduced ejection fraction (EF), with or without diabetes.
The findings presented at the European Society of Cardiology 2020 digital congress and simultaneously published in The New England Journal of Medicine are “virtually superimposable” on the DAPA-HF results from last year, said presenter Milton Packer (Baylor Heart and Vascular Institute, Dallas, Texas, USA).
However, EMPEROR-Reduced had a slightly different patient population because the investigators had aimed to recruit more people with an EF below 30%; people with an EF of 31–40% were enrolled only if they had been hospitalized for HF within the preceding 12 months or had a particularly high N-terminal prohormone of brain natriuretic peptide levels (cutoff of 1000 or 2500 pg/mL depending on EF).
The average EF in EMPEROR-Reduced was therefore around 27%, compared with 31% in DAPA-HF, representing patients with more severe albeit stable disease.
Addressing the press, Packer described the combined results of the two sodium-glucose cotransporter (SGLT)2 inhibitor trials as “practice changing” and said: “I believe – and I think others share this view – there’s now compelling evidence that SGLT2 inhibitors should be added to currently recommended treatments for [HF with reduced EF].”
During a median 16 months of treatment, 19.4% of the 1863 patients randomly assigned to take empagliflozin 10 mg/day had a primary endpoint event of death from cardiovascular causes or hospitalization for HF, compared with 24.7% of the 1867 patients taking placebo.
This equated to a 25% relative difference favoring empagliflozin treatment, which was exactly the size of the reduction seen in DAPA-HF. The difference was driven by a significant 31% reduction in the risk for first HF hospitalization, whereas there was a nonsignificant 8% reduction in cardiovascular mortality risk.
Around half (49.8%) of the EMPEROR-Reduced participants had type 2 diabetes, and Packer reported that the effect of empagliflozin on the primary endpoint was very similar in those with and without the condition, giving risk reductions of 28% and 22%, respectively.
There were also two major prespecified secondary outcomes in EMPEROR-Reduced, both of which significantly favored empagliflozin. The first was the total number of HF hospitalizations, for which there were 388 versus 553 events in the empagliflozin and placebo groups, respectively, giving a 30% risk reduction. The second was the annual rate of decline in estimated glomerular filtration rate, which was 0.55 versus 2.28 mL/min per 1.73 m2, respectively.
In an editorial accompanying the publication, John Jarcho (Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA) writes: “The results of the EMPEROR-Reduced trial confirm that the findings in DAPA-HF were no fluke and substantially strengthen the rationale for the use of SGLT2 inhibitors in patients with heart failure and a reduced ejection fraction.”
He concludes: “Guidelines committees will now need to contend with the evidence.”
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