Breakthrough results for empagliflozin confirm EMPEROR-Preserved as first and only successful trial for heart failure with preserved ejection fraction

The EMPEROR-Preserved Phase III trial met its primary endpoint, establishing empagliflozin as the first and only therapy to significantly reduce the risk of the composite of cardiovascular death or hospitalization for heart failure in adults, with or without diabetes, who live with heart failure with preserved ejection fraction (HFpEF). Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced the topline results in July 2021. When added to the EMPEROR-Reduced trial results, these findings demonstrate empagliflozin’s efficacy in all forms of heart failure regardless of ejection fraction. The safety profile was generally consistent with the known safety profile of empagliflozin.

“The EMPEROR-Preserved results represent a significant 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,” said Stefan Anker, Professor of Cardiology, Charité Campus Virchow-Klinikum, Germany, and EMPEROR-Preserved Principal Investigator. “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.”

Heart failure poses a significant global disease burden: more than 60 million patients worldwide have heart failure and half of them have HFpEF.[iii],[iv] Heart failure is a leading cause of hospitalization and is becoming increasingly prevalent in Western countries due to aging populations.3 The risk of death in people with heart failure rises with each hospital admission.[v] Heart failure with left ventricular preserved ejection fraction occurs when the left ventricle of the heart is unable to fill properly, resulting in less blood being pumped to the body.[vi]

“Heart failure is a prevalent and life-limiting condition and studies[vii] show that this condition affects patients in the Middle East a decade earlier in comparison to Western countries,” said Mohammed Al-Tawil, Regional Managing Director and Head of Human Pharma, Boehringer Ingelheim Middle East, Turkey and Africa. “There are limited treatment options for patients who have heart failure, especially with preserved ejection fraction, and these results present opportunities to better serve the needs of patients. Together with the earlier EMPEROR-Reduced trial results, we now have a potential solution that treats the full spectrum on heart failure.”

“Prior to the EMPEROR-Preserved topline results, there were no clinical studies demonstrating reduced risk of heart failure hospitalizations or cardiovascular mortality for all adults for this particular condition. This is a significant milestone with Empagliflozin as studies continue to explore its effect across a wider spectrum of cardio-renal-metabolic diseases. With these results, we can look forward to being able to expand the use of empagliflozin in the treatment for heart failure, whether related or unrelated to Type 2 Diabetes,” said Dr Mohamed Meshref, Medical Director for Middle East Turkey and Africa, Boehringer Ingelheim.

The EMPEROR-Preserved trial investigated empagliflozin 10 mg compared to placebo.[viii] Full results from the EMPEROR-Preserved trial are scheduled for presentation at the European Society of Cardiology (ESC) Congress 2021 on 27 August.

These results add to previous findings from the EMPEROR-Reduced Phase III trial, which showed that in patients with heart failure with reduced ejection fraction (HFrEF) with or without Type 2 diabetes, empagliflozin significantly reduced the combined relative risk of cardiovascular death or hospitalization for heart failure by 25 percent, compared to placebo.[ix] Together, these studies demonstrate the benefits of empagliflozin for patients across the full heart failure spectrum (including HFrEF and HFpEF).

The EMPEROR-Reduced results formed the basis of the recent approval of a new indication for empagliflozin for the treatment of adults with HFrEF by the European Commission.[x] A supplemental New Drug Application (sNDA) for empagliflozin to reduce the risk of cardiovascular death or hospitalization for heart failure in adults with HFrEF has been submitted to the U.S. Food and Drug Administration (FDA), with a decision expected later this year.[xi] Empagliflozin is currently indicated for the treatment of adults with insufficiently controlled type 2 diabetes (additionally, in the E.U. for the treatment of adults with HFrEF). 9,[xii],[xiii],[xiv]

Research is ongoing regarding empagliflozin’s effects on hospitalization for heart failure and mortality in post-myocardial infarction (heart attack) patients with high risk of heart failure.[xv] Empagliflozin is also currently being investigated in chronic kidney disease.[xvi]

 

 

[i] Butler J, Fonarow G, Zile M, et al. Developing therapies for heart failure with preserved ejection fraction: Current State and Future Directions. JACC Heart Fail. 2014 Apr;2(2):97–112.

[ii] Shah SJ, Borlaug B, Kitzman D, et al. Research priorities for heart failure with preserved ejection fraction. Circulation. 2020;141:1001–26.

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

[iv] 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.

[v] Solomon S, Dobson J, Pocock S, et al. Influence of Nonfatal Hospitalization for Heart Failure on Subsequent Mortality in Patients With Chronic Heart Failure. Circulation. 2007;116(13):1482–7.

[vi] 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: July 2021

[vii] Hassan M. Gulf CARE: Heart failure in the Middle East, Global Cardiology Science and Practice 2015:34 http://dx.doi.org/10.5339/gcsp.2015.34. Accessed: July 2021

[viii] ClinicalTrials.gov. EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved). Available at: https://clinicaltrials.gov/ct2/show/NCT03057951. Accessed: July 2021.

[ix] Packer M, Anker SD, Butler J, et al. Cardiac and Renal Outcomes With Empagliflozin in Heart Failure With a Reduced Ejection Fraction. N Engl J Med. 2020;383:1413–24.

[x] Committee for Medicinal Products for Human Use (CHMP). Jardiance summary of opinion (post authorisation). Available at: https://www.ema.europa.eu/en/documents/smop/chmp-post-authorisation-summary-positive-opinion-jardiance-ii-55_en.pdf. Accessed: July 2021.

[xi] Boehringer Ingelheim press release. US FDA accepts supplemental New Drug Application for Jardiance® (empagliflozin) for adults with heart failure with reduced ejection fraction. Available at: https://www.boehringer-ingelheim.us/press-release/us-fda-accepts-supplemental-new-drug-application-jardiance-empagliflozin-adults-heart. Accessed: July 2021.

[xii] Jardiance® (empagliflozin) tablets, U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed: July 2021.

[xiii] Jardiance® (empagliflozin) tablets. European Product Information, approved April 2020. Available at: https://www.ema.europa.eu/en/documents/product-information/jardiance-epar-product-information_en.pdf. Accessed July 2021.

[xiv] Jardiance® (Full Prescribing Information). Egypt, Jordan, Oman, UAE ; Boehringer Ingelheim

Middle East & North Africa (Scientific Office); Access July 2021.

[xv] 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 July 2021.

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

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