EMPEROR-Preserved First Trial to Show Positive Results in HFpEF

A statement from the makers of the SGLT2 inhibitor empagliflozin suggests the benefits in heart failure with preserved ejection fraction (HFpEF) are significant.

For the first time, a clinical trial has successfully shown that a therapy can cut the risk of hospitalization and cardiovascular death for patients with heart failure with preserved ejection fraction (HFpEF), as top-line results from EMPEROR-Preserved were released for empagliflozin (Jardiance).

The long-awaited results, which will be presented in late August during the European Society of Cardiology 2021, will show that the sodium glucose co-transporter 2 (SGLT2) inhibitor meets “the single largest unmet need in cardiovascular medicine,” according to a statement from the drug’s sponsors, Eli Lilly and Boehringer Ingelheim.

Earlier this year, Novartis won FDA approval for sacubitril/valsartan (Entresto) in HFpEF, even though the therapy just missed achieving superiority in a critical phase 3 trial; instead, regulators evaluated a body of evidence across several studies and noted that subsets of patients had better outcomes.

The statement from the drug’s sponsors suggests that the EMPEROR-Preserved results will show that the benefit in HFpEF is substantial.

“We look forward to presenting the EMPEROR-Preserved results at ESC 2021, which should offer a breakthrough in cardiovascular medicine and a new hope for people with HFpEF, which is an increasingly prevalent public health issue. HFpEF has long been the most challenging form of heart failure to treat,” Professor Stefan Anker, heart failure cardiologist at Charité Berlin, Germany, and EMPEROR-Preserved principal investigator, said.

“Building on previous results from the EMPA-REG-OUTCOME trial, and the EMPEROR-Reduced trial in heart failure with reduced ejection fraction, the EMPEROR-Preserved findings demonstrate that empagliflozin reduces cardiovascular death or hospitalization for heart failure and has the potential to transform the care of people living with heart failure.”

EMPA-REG OUTCOME was the groundbreaking study presented in September 2015 that showed for the first time that the SGLT2 inhibitor, which had been developed to treat type 2 diabetes (T2D), not only safely avoided any cardiovascular (CV) harms, but also produced CV benefits—notably the reduction of heart failure hospitalization and a reduction in CV death.

The reduction in heart failure hospitalization would be seen across the SGLT2 class, putting manufacturers in a race to rethink the drug’s use as treatment for heart failure as well. In fact, following EMPA-REG OUTCOME, AstraZeneca moved to add a second primary end point that included heart failure to its CV outcomes trial for its drug, dapagliflozin (Farxiga).

While the EMPEROR-Preserved results are big news, the results are not a complete surprise. Results from studies involving a dual SGLT1/2 inhibitor, sotagliflozin, have shown a signal for effectiveness in HFpEF, and the lead author, Deepak L. Bhatt, MD, MPH, of Harvard and Brigham and Women’s Hospital, recently predicted that upcoming trials involving empagliflozin and dapagliflozin would have positive results.

HFpEF occurs when the left ventricle is unable to fill properly, causing an inadequate amount of blood to be pumped through the body, depriving the body and organs of adequate oxygen. The condition affects about 30 million people worldwide. It is a leading cause of hospitalization, and in the United States, Medicare has pressed health systems to develop ways to better care for these patients, who typically have other comorbidities and are often repeatedly readmitted at great cost of the health system. The risk of death rises each time a person is hospitalized with heart failure.