Treatment with empagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure and slowed kidney function decline in adults with heart failure and left ventricular ejection fraction (LVEF) over 40% regardless of chronic kidney disease (CKD) status, according to new prespecified sub-analysis of the phase 3 EMPEROR-Preserved trial.
The randomized, double-blind trial (ClinicalTrials.gov Identifier: NCT03057951) compared the efficacy and safety of empagliflozin with placebo in 5988 adults with heart failure and preserved ejection fraction (HFpEF), with and without diabetes. Patients were randomly assigned 1:1 to receive either empagliflozin 10mg once daily (n=2997) or placebo (n=2991), in addition to standard of care for up to 38 months. The composite primary endpoint of the study was the time to first event of adjudicated cardiovascular death or adjudicated hospitalization for heart failure.
At trial entry, 67% of patients had HFpEF (LVEF at least 50%) and 33% had mildly reduced LVEF (40% to 49%). Moreover, 53.5% of patients had CKD (estimated glomerular filtration rate [eGFR] less than 60mL/min/1.73m2 or urine albumin-to-creatinine ratio greater than 300mg/g), and 9.7% had severe kidney impairment (eGFR less than 30mL/min/1.73m2).
According to the new prespecified sub-analysis, empagliflozin demonstrated consistent improvement in cardiovascular outcomes and slowed kidney function decline in adults with and without CKD. The improvements were observed across a full range of kidney function down to an eGFR of 20mL/min/1.73m2. As for safety, empagliflozin was well tolerated regardless of baseline kidney function.
In September 2021, the Food and Drug Administration (FDA) granted Breakthrough Therapy designation to empagliflozin for the treatment of adults with HFpEF. The designation was based on previously reported findings from the EMPEROR-Preserved trial.
“Heart failure, especially with preserved ejection fraction, is a complex, difficult-to-treat condition, and the prognosis only worsens with the combined burden of chronic kidney disease,” said Mohamed Eid, MD, MPH, MHA, vice president, Clinical Development & Medical Affairs, Cardio-Metabolism & Respiratory Medicine, Boehringer Ingelheim Pharmaceuticals, Inc. “The encouraging results from this sub-analysis further demonstrate the potential for Jardiance to offer a treatment option for adults with cardio-renal-metabolic conditions.”
Empagliflozin is marketed under the trade name Jardiance. In August 2021, the FDA approved Jardiance to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with chronic heart failure with reduced ejection fraction.
The approval was based on data from the phase 3 EMPEROR-Reduced trial (ClinicalTrials.gov Identifier: NCT03057977), which demonstrated that treatment with empagliflozin reduced the combined relative risk of cardiovascular death or hospitalization for heart failure by 25% compared with placebo in adults with heart failure with reduced ejection fraction.
Jardiance® shows consistent cardio-renal benefits in adults with heart failure with left ventricular ejection fraction over 40% regardless of chronic kidney disease status. News release. Eli Lilly and Company. November 5, 2021. Accessed November 8, 2021. https://www.prnewswire.com/news-releases/jardiance-shows-consistent-cardio-renal-benefits-in-adults-with-heart-failure-with-left-ventricular-ejection-fraction-over-40-regardless-of-chronic-kidney-disease-status-301417725.html.