EMPEROR-Preserved: Empagliflozin lowers CV death, hospitalization in heart failure patients with preserved ejection fraction
A landmark trial reveals sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin is the first therapy to show significant improvement in heart failure outcomes in adults with preserved ejection fraction.
Heart failure with preserved ejection fraction (HFpEF), also known as diastolic heart failure, happens when the left ventricle cannot fill completely with blood during the diastolic phase. The ejection fraction is ≥50 percent when the ventricle can pump well. HFpEF may also be diagnosed if the ejection fraction is 40–49 percent. [https://www.uofmhealth.org/health-library/tx4091abc]
The EMPEROR-Preserved* trial included 5,988 patients with NYHA class II–IV heart failure and left ventricular ejection fraction (LVEF) >40 percent and estimated glomerular filtration rate of ≥20 mL/min/1.73 m2. They were randomly assigned to receive either empagliflozin 10 mg once daily (n=2,997) or placebo (n=2,991) and followed up for about 26 months.
This phase III trial has shown empagliflozin-treated patients with heart failure and preserved ejection fraction (HFpEF) showed 21 percent relative risk reduction for the composite primary endpoint of cardiovascular death or hospitalization for heart failure compared with the placebo group (hazard ratio [HR], 0.79; 95 percent confidence interval [CI], 0.69–0.90; p<0.001). [N Engl J Med 2021 Aug 27. doi: 10.1056/NEJMoa2107038. Available at: https://pubmed.ncbi.nlm.nih.gov/34449189/]
Key secondary endpoint analyses from the trial, presented at the European Society of Cardiology (ESC) Congress 2021, showed empagliflozin (Jardiance®, Boehringer Ingelheim) reduced the relative risk of first and recurrent hospitalizations for heart failure by 27 percent (HR, 0.73; 95 percent CI, 0.61–0.88; p<0.001).
“[EMPEROR-Preserved] data brings hope for millions of patients suffering from HFpEF. The primary endpoint was similarly improved in all subgroups of patients, in men and women, with and without diabetes ... This underlines the breadth of the SGLT2 inhibitor’s efficacy and its potential overall impact,” said Professor Stefan Anker, principal investigator of EMPEROR-Preserved, and heart failure cardiologist at Charité Berlin, Germany, during a recent virtual press conference.
He added that HFpEF patients with or without diabetes can be safely treated with empagliflozin. There were no issues related to ketoacidosis, hypoglycaemia, and limb amputation in the EMPEROR-Preserved trial. However, some patients in the empagliflozin group had symptomatic hypotension (1.4 percent) and genital infections (1.5 percent) vs placebo. While hypotension can be managed either by reassuring the patients or halving the diuretics dose, genital mycotic infections can be prevented by providing personal hygiene advice to patients. [Ann Pharmacother 2021;55:543–548]
GPs should suspect heart failure when patients present with shortness of breath and oedema in the legs, which resolve when treated with diuretics. Patients need to be diagnosed using echocardiography and biomarker tests. Hence, a referral to the cardiologist is recommended, said Anker.
“We are quite excited with the results [of EMPEROR-Preserved] giving us a new avenue in terms of potential treatment for patients with HFpEF,” said Dato’ Dr Azmee Mohd Ghazi, clinical director of Heart Failure and Heart Transplant, National Heart Institute (IJN). He foresees SGLT2 inhibitors being included in the CPG on management of heart failure for patients with HFpEF.
The IJN’s Acute Decompensated Heart Failure Registry 2009–2018 showed about half of the patients with heart failure had HFpEF and they were older (an average of 67 years), higher proportion were women; they had multiple comorbidities like diabetes, hypertension, and dyslipidaemia, and were at high risk of readmission and death, said Azmee.