Empagliflozin Demonstrates Consistent Cardiorenal Benefits in Adults with Heart Failure and LVEF >40%, Regardless of Baseline Chronic Kidney Disease Status

Ingelheim, Germany and Indianapolis, USA, November 19, 2021 /PRNewswire/ -- Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced results from a newly disclosed pre-specified subgroup analysis of the EMPEROR-Preserved® Phase III clinical trial. The analysis showed that empagliflozin reduced the composite risk of cardiovascular death or hospitalization for heart failure in adults with heart failure and left ventricular ejection fraction (LVEF) over 40%, regardless of baseline chronic kidney disease status, and slowed kidney function decline. In the EMPEROR-Preserved® trial, two-thirds of the enrolled adults had heart failure with preserved ejection fraction (HFpEF; LVEF at least 50%), while one-third had mildly reduced LVEF (greater than 40% but less than 50%). These findings were presented at the American Society of Nephrology Kidney Week 2021.

"Heart failure and chronic kidney disease are closely related – the risk of death in heart failure patients increases as renal function declines," said Faiez Zannad, M.D., Ph.D., Professor Emeritus of Therapeutics and Cardiology at the University of Lorraine, France, and clinical trial investigator for the EMPEROR program. "Consistent benefits in reducing serious heart failure events and slowing kidney function decline were demonstrated regardless of a patient’s chronic kidney disease status, which is a welcome outcome for both patients and physicians. These findings underscore the potential value of empagliflozin across a broad population of heart failure patients with varying kidney function, including those with heart failure with preserved ejection fraction."

Nearly half of adult patients with heart failure also suffer from chronic kidney disease.^[1]Moreover, these diseases are associated with high mortality and hospitalization risks.^[3]More than 60 million people worldwide suffer from heart failure, approximately half of whom have HFpEF.^[2],[3]There are currently no approved therapies that have been clinically validated to significantly improve treatment outcomes for various types of heart failure.

Waheed Jamal, MD, Vice President of Boehringer Ingelheim and Head of Cardio-Metabolic Medicine, stated: "For heart failure patients, including those with chronic heart failure with preserved ejection fraction, chronic kidney disease presents additional challenges in managing these patients and contributes to the worsening and progression of heart failure. The data from the EMPEROR-Preserved® clinical trial are very encouraging, as the evidence shows that empagliflozin provides benefits to the heart and kidneys of heart failure patients, including those with HFpEF and coexisting chronic kidney disease."

As previously announced, the EMPEROR-Preserved® clinical trial met its primary endpoint, showing that empagliflozin significantly reduced the composite risk of cardiovascular death or hospitalization for heart failure in adult heart failure patients with LVEF greater than 40% compared to placebo. Empagliflozin also significantly reduced the risk of both first and recurrent hospitalizations for heart failure and slowed the decline in kidney function.

In the EMPEROR-Preserved® clinical trial, more than half (53.5%) of adult patients had chronic kidney disease at the start of the trial (defined as eGFR below 60 ml/min/1.73 m²or UACR higher than 300 mg/g), and 9.7% of adult patients have severe renal impairment (eGFR below 30 ml/min/1.73m²）。^[1]Newly disclosed pre-specified subgroup analyses from the EMPEROR-Preserved® clinical trial show that the benefits observed in the overall population were consistent in adult patients with or without chronic kidney disease. Regardless of renal function status, empagliflozin demonstrated consistency in improving cardiovascular outcomes and slowing renal function decline, even as eGFR decreased to 20 mL/min/1.73 m².^[1]Empagliflozin was well tolerated regardless of the patient's baseline renal function.^[1]

"For the growing number of patients with both heart failure and chronic kidney disease, these data represent an important milestone, as they need more treatment options to address these interconnected and complex conditions," said Jeff Emmick, M.D., Ph.D., Vice President of Product Development at Eli Lilly and Company. "We look forward to continuing our research to meet the unmet needs of patients with impaired kidney function, including through our EMPA-KIDNEY Phase III clinical trial with empagliflozin, and we eagerly anticipate the study results next year."

Empagliflozin is currently used to treat adult patients with type 2 diabetes. Additionally, empagliflozin has been approved in the EU and the United States for the treatment of adult patients with HFrEF, with or without diabetes.^[6],[7]Boehringer Ingelheim and Eli Lilly Diabetes Alliance Plan to Submit HFpEF Indication Registration Application Worldwide in 2021. A study on the impact of empagliflozin on heart failure hospitalization risk and mortality in high-risk heart failure patients post-myocardial infarction (heart attack) is currently underway.^[4]Empagliflozin is also currently being studied for the treatment of chronic kidney disease.^[5]

References

^[1] Banerjee D, Wang AY. Personalizing heart failure management in chronic kidney disease patients. Nephrol Dial Transplant. 2021;doi:10.1093/ndt/gfab026.

^[2] Andersen MJ, Borlaug BA. Heart failure with preserved ejection fraction: current understandings and challenges. Curr Cardiol Rep. 2014;16(7):501.

^[3] GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–858.

^[4] ClinicalTrials.gov. EMPACT-MI: A Study to Test Whether Empagliflozin Can Lower the Risk of Heart Failure and Death in People Who Had a Heart Attack (Myocardial Infarction). Available at: https://clinicaltrials.gov/ct2/show/NCT04509674. Accessed: October 2021.

^[5] ClinicalTrials.gov. EMPA-KIDNEY (The Study of Heart and Kidney Protection With Empagliflozin). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03594110. Accessed: October 2021.

^[6] GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016; 388(10053):1459–544.

^[7] American Heart Association. Types of Heart Failure. Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/types-of-heart-failure. Accessed: September 2021.