medwireNews: Empagliflozin has become the first medication to demonstrate a clear protective effect in people with heart failure and preserved ejection fraction (HFpEF), report the EMPEROR-Preserved investigators.
Presenting the findings to press attendees at the virtual ESC Congress 2021, Stefan Anker (Charité Universitätsmedizin Berlin, Germany) showed the topline results of HFpEF trials dating back to 2003. None of the medications used in these trials produced a significant reduction in HF outcomes, although a couple showed a strong trend toward a positive effect.
By contrast, people taking empagliflozin 10 mg/day in EMPEROR-Preserved had a highly significant (p=0.0003) 21% reduction in the risk for the primary composite outcome of HF hospitalization or cardiovascular death relative to those given placebo.
EMPEROR-Preserved investigator Stefan Anker discusses the role of SGLT2 inhibitors in patients with heart failure.
In all, 13.8% of the 2997 trial participants randomly assigned to take empagliflozin had a primary outcome event over a median 26.2 months, compared with 17.1% of the 2991 given placebo. This gave a number needed to treat of 31 to prevent one primary outcome event.
The participants all had HF New York Heart Association class II–IV (<80% had class II HF), with a left ventricular ejection fraction (LVEF) greater than 40%. Their average age was 72 years, 45% were women, and 49% had diabetes.
The benefit on the primary composite outcome was seen almost immediately, with the event rates clearly diverging within the first month, and was driven by a 27% reduction in the risk for HF hospitalization. The positive effect on the primary composite outcome was consistent across all assessed subcategories, including the presence or absence of diabetes and baseline LVEF, although the effect tended to be greater at lower EFs.
The findings were simultaneously published in The New England Journal of Medicine, in which editorialist Mark Drazner (University of Texas Southwestern Medical Center, Dallas, USA) describes them as “a major win against a medical condition that had previously proved formidable.”
He writes: “Ultimately, the EMPEROR-Preserved trial should contribute to a change in clinical practice, given the paucity of therapeutic options available for patients with heart failure and a preserved ejection fraction.”
Also published in the same journal is a pooled analysis of EMPEROR-Preserved and EMPEROR-Reduced, including a total of 9718 trial participants. This analysis revealed significant heterogeneity between the two trials for the effect of empagliflozin on serious renal outcomes.
Kevin Fernando discusses the EMPEROR-Preserved findings and their likely impact on the treatment of people with heart failure with preserved ejection fraction, with or without diabetes, in primary care.
Participants in the HFrEF trial had a significant 49% risk reduction for a “profound and sustained” estimated glomerular filtration rate (eGFR) reduction or need for renal-replacement therapy if they took active rather than placebo treatment.
However, for people with a preserved EF, empagliflozin treatment was associated with a nonsignificant 5% reduction in the risk. This was despite its use being associated with a significant reduction in the decline of eGFR, of 1.36 mL/min per 1.73 m2.
This suggests “that eGFR slope analysis has limitations as a surrogate for predicting the effect of drugs on renal outcomes in patients with heart failure,” write Milton Packer (Baylor University Medical Center, Dallas, Texas, USA) and study co-authors.
The researchers also highlight the contrast with HF outcomes; empagliflozin reduced the risk for HF hospitalization to a similar extent in both EMPEROR trials.
And in his editorial, Drazner notes: “On the basis of these findings, it seems likely that renal protection is not the main mechanism by which empagliflozin prevents hospitalization for heart failure.”
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