During a recent PW Podcast episode, we spoke with ESC 2021 plenary talk presenter Stefan Anker, MD, PhD, about the full results of the EMPEROR Preserved trial, which affirm that empagliflozin lowers the risk of CVD in patients with heart failure (HF) and HF with preserved ejection fraction (HFpEF), leading one expert to say this is “a big day for patients living with HFpEF, a big day for heart failure clinicians.”
What makes the results from the EMPEROR-Preserved trial significant?
EMPEROR-Preserved is the first positive clinical trial with meaningful results for patients with HFpEF. SGLT2 inhibitors work in HF with reduced EF, which has been reported in several trials during the last couple years. Now, we are focusing on HFpEF, for which guidelines do not recommend any specific therapy, because the trials in this field narrowly missed their target of achieving significance.
With EMPEROR-Preserved, recruiting 6,000 patients over the last 3.5 years and following them for 26 months on average, we are looking at empagliflozin 10 mg once daily versus placebo. And for the first time, we are able to report a 21% reduction in the primary endpoint of cardiovascular mortality and HF hospitalization, with a P value of 0.0003.
These results are meaningful and important for these patients and hopefully will lead to a standardization of therapy in the HFpEF field. They are driven by HF hospitalization reductions. First and recurrent HF hospitalization had a 27% reduction with empagliflozin compared with placebo, with a P value of 0.001, again a meaningful result. The second component of the primary endpoint, cardiovascular mortality, was reduced by 9%, not achieving significance but contributing overall to the primary endpoint.
We observed a positive impact on the secondary endpoint—change in eGFR slope—in EMPEROR-Reduced, along with a reduction in renal events. In EMPEROR-Preserved, we also saw a highly significant impact on the eGFR slope over time but unfortunately no impact on renal events, perhaps due to too short a follow up or issues with how we defined these events. We also observed significant improvements in quality-of-life measures and symptomatic status.
There were no new safety signals that should give patients or clinicians concern. Indeed, keto acidosis occurred in four versus five cases in the 3,000 patients, respectively, in the two treatment arms. And as expected, genital tract infections were somewhat increased, at 2.2% versus 0.7%. These results suggest that we need to continue efforts for hygiene advice with patients. There was a small increase of hypotension: 10.4% versus 8.6%. Results were neutral on all-cause mortality, with a hazard ratio of 1.00.
All-around, this study tells us that empagliflozin can be safely used for treating HFpEF.