Empagliflozin reduces hospitalization and mortality in HF with preserved EF, NEJM.

Although pharmacologic therapies that improve clinical outcomes have been identified for use in patients with heart failure and a reduced ejection fraction, there has been far less progress in treatment for those with a preserved ejection fraction. The results of the EMPEROR-Preserved trial now published in NEJM have shown significant reduction in the combined risk of cardiovascular death or hospitalization with empagliflozin in patients with heart failure and a preserved ejection fraction (HFpEF), regardless of the presence or absence of diabetes.

SGLT2 inhibitors empagliflozin and dapagliflozin have been shown to reduce the risk of hospitalization for heart failure and cardiovascular death in patients with chronic heart failure and a reduced ejection fraction. However, prospective, clinical trials of SGLT inhibitors in patients with chronic heart failure and a preserved ejection fraction are need of the hour.

The EMPEROR-Preserved trial enrolled 5988 patients with heart failure and an ejection fraction of more than 40%; most patients (82%) had New York Heart Association class II heart failure.

Patients were randomly assigned to receive either empagliflozin at a dose of 10 mg per day or placebo and were followed for a median of 26.2 months. The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure. The trial had following major results:

1. The risk of cardiovascular death or hospitalization for worsening heart failure was lower in the empagliflozin group than in the placebo group by 21%.

2. This effect was mainly related to a 29% lower risk of hospitalization for heart failure in the empagliflozin group.

3. A benefit of empagliflozin was also seen with respect to the secondary outcome of the total number of hospitalizations for heart failure.

4. There was a nonsignificant 9% lower risk of death from cardiovascular causes in the empagliflozin group than in the placebo group.

5. The benefit of empagliflozin with respect to the primary outcome was independent of diabetes status.

Although the effect on mortality is not very robust but Mark H. Drazner, M.D. mentions in an accompanying editorial that "Nevertheless, it will be interesting to see whether dapagliflozin reduces cardiovascular mortality in the DELIVER trial in patients with a preserved ejection fraction such that the results of the DELIVER and EMPEROR-Preserved trials would mirror the pattern of results of the DAPA-HF and EMPEROR-Reduced trials in patients with a reduced ejection fraction".

The EMPEROR-Preserved trial is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome, a result that represents a major win against a medical condition that had previously proved formidable. The DELIVER trial may confirm the benefits of SGLT2 inhibition in patients with an ejection fraction of more than 40%. 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.

Source: NEJM:

1. DOI: 10.1056/NEJMoa2107038

2. DOI: 10.1056/NEJMe2113008