Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction. That's the finding of the EMPEROR-Reduced trial presented in a Hot Line session today at ESC Congress 2020.
The EMPEROR-Reduced trial was designed to evaluate the effects of empagliflozin 10 mg once daily (as compared with placebo) in patients with heart failure and a reduced ejection fraction, with or without diabetes, who were already receiving all appropriate treatments for heart failure.
The primary endpoint was the composite of cardiovascular death or hospitalisation for heart failure. Secondary endpoints included adverse renal outcomes, defined as chronic dialysis or renal transplant or sustained reduction of estimated glomerular filtration rate (eGFR).
By adjusting eligibility based on natriuretic peptide levels to the baseline ejection fraction, the trial preferentially enrolled higher-risk patients, who had not been well-represented in earlier studies.
The trial enrolled 3,730 patients with heart failure and a left ventricular ejection fraction of 40% or less, with or without diabetes. Patients were randomly assigned to empagliflozin 10 mg once daily or placebo.
During a median follow-up of 16 months, the primary endpoint occurred in 361 patients in the empagliflozin group and 462 patients in the placebo group (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.65-0.86; p<0.0001). Empagliflozin reduced total hospitalisations for heart failure (HR 0.70; 95% CI 0.58-0.85; p<0.001).
Adverse renal outcomes occurred in 30 patients in the empagliflozin group and 58 patients in the placebo group (HR 0.50; 95% CI 0.32-0.77; p<0.01).
Uncomplicated genitourinary tract infections were more common in the empagliflozin group (1.3% vs. 0.4%), but the frequency of hypotension, volume depletion and hypoglycaemia were similar in the two groups.
Principal investigator Dr. Milton Packer of Baylor University Medical Centre, Dallas, Texas said: "Empagliflozin reduced the risk of serious heart failure events by 30% and decreased the risk of serious adverse renal outcomes by 50%. This trial extends the benefits of SGLT2 inhibitors to higher-risk patients and shows a meaningful benefit on renal outcomes in patients with heart failure for the first time."
Dr. Packer said: "Based on the combined results of our trial (together with the earlier trial with dapagliflozin), we believe that SGLT2 inhibition with empagliflozin and dapagliflozin will now become a new standard of care for patients with heart failure and a reduced ejection fraction."
Packer M., et al. (2020) Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. The New England Journal of Medicine. doi.org/10.1056/NEJMoa2022190.