Jardiance (Empagliflozin) Reduces Risk of Cardiovascular Death or Hospitalization by 21% in HFpEF Patients, Becoming First SGLT2 Inhibitor to Cover Both Major Heart Failure Types

On August 27, 2021, Boehringer Ingelheim and Eli Lilly and Company jointly announced positive results from the Phase 3 EMPEROR-Preserved clinical trial of the SGLT2 inhibitor empagliflozin (brand name Jardiance). The trial met its composite primary endpoint, demonstrating that empagliflozin reduced the relative risk of cardiovascular death or hospitalization for heart failure by 21% in adult patients with heart failure with preserved ejection fraction (HFpEF) compared with placebo.

Earlier this month, the U.S. FDA approved the drug to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with heart failure with reduced ejection fraction (HFrEF). The press release noted that the benefits on the primary endpoint of this Phase 3 clinical trial were independent of patients' ejection fraction or diabetes status, positioning empagliflozin as the first therapy expected to significantly improve survival outcomes across the full spectrum of heart failure patients. The relevant results were presented today at the European Society of Cardiology (ESC) Congress 2021 and published in *The New England Journal of Medicine*. At the end of last year, the two companies also submitted a registration application for empagliflozin to China's National Medical Products Administration (NMPA) for the treatment of adult patients with heart failure with reduced ejection fraction, with or without diabetes.

Empagliflozin is a highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor administered orally once daily. In patients with type 2 diabetes and elevated blood glucose levels, empagliflozin inhibits SGLT2, thereby preventing renal glucose reabsorption and promoting urinary glucose excretion. Additionally, empagliflozin inhibits sodium reabsorption, which increases sodium excretion and reduces the fluid load on the cardiovascular system. The metabolic changes in glucose, sodium, and water induced by empagliflozin may contribute to a reduction in cardiovascular mortality.

The EMPEROR-Preserved trial enrolled a total of 5,988 patients. Of these, 4,005 had a left ventricular ejection fraction (LVEF) ≥50%, and 1,983 had an LVEF <50%. In the trial, participants were randomized to receive once-daily 10 mg empagliflozin (n=2,997) or placebo (n=2,991). In addition to meeting the primary endpoint, the trial also achieved its key secondary endpoint, demonstrating that empagliflozin reduced the relative risk of first and recurrent hospitalizations for heart failure by 27% and significantly slowed the decline in renal function. Regarding safety, the overall safety data were consistent with previous results, confirming the established safety profile of the drug.

▲ Primary and key secondary endpoint data from the EMPEROR-Preserved trial (Image source: Reference [2])

Heart failure is classified into HFrEF and HFpEF. HFrEF occurs when the myocardium fails to contract effectively, resulting in the heart pumping less blood into the body. HFpEF occurs when the myocardium contracts normally but the ventricles cannot fill with adequate blood, resulting in less blood entering the heart.

The Phase 3 EMPEROR-Reduced trial, which previously enrolled a total of 3,730 patients with HFrEF (with or without type 2 diabetes), demonstrated that compared with placebo, empagliflozin reduced the risk of the composite endpoint of cardiovascular death and hospitalization for heart failure by 25% (HR=0.75, 95% CI 0.65–0.86).

References:

[1] Landmark trial demonstrates Jardiance^® (empagliflozin) is the first therapy to show statistically significant improvement in heart failure outcomes in adults with preserved ejection fraction. Retrieved from https://www.prnewswire.com/news-releases/landmark-trial-demonstrates-jardiance-empagliflozin-is-the-first-therapy-to-show-statistically-significant-improvement-in-heart-failure-outcomes-in-adults-with-preserved-ejection-fraction-301364113.html

[2] Anker et al., (2021). Empagliflozin in Heart Failure with a Preserved Ejection Fraction.NEJM, DOI: 10.1056/NEJMoa2107038

▽Follow 【WuXi AppTecGermany】WeChat Official Account