Landmark clinical trial demonstrates empagliflozin (Jardiance®) is the first therapy to show statistically significant improvement in heart failure outcomes in adults with preserved ejection fraction (HFpEF)

Landmark clinical trial demonstrates empagliflozin (Jardiance^®) is the first therapy to show statistically significant improvement in heart failure outcomes in adults with preserved ejection fraction (HFpEF)

• Empagliflozin demonstrated a significant 21 percent relative risk reduction (absolute risk reduction, ARR, 3.3%) in the composite primary endpoint of cardiovascular death or hospitalisation for heart failure in adults with heart failure with preserved ejection fraction[i]
• The benefit was independent of ejection fraction or diabetes status in predefined subgroups for the primary endpoint¹
• Empagliflozin also reduced the relative risk of first and recurrent hospitalisations for heart failure by 27 percent (ARR 4.5%)²⁸ and significantly slowed kidney function decline¹
• Results from the Phase 3 EMPEROR-Preserved trial were presented today at the European Society of Cardiology Congress 2021[ii] and published in The New England Journal of Medicine¹

Bracknell, UK, 27 August 2021 – Full results from the landmark EMPEROR-Preserved Phase 3 trial demonstrated that empagliflozin (Jardiance^®) showed a significant 21 percent relative risk reduction (absolute risk reduction 3.3%; hazard ratio 0.79; 95% confidence interval: 0.69 to 0.90; p<0.001) for the composite primary endpoint of cardiovascular death or hospitalisation for heart failure in adults with heart failure with preserved ejection fraction (HFpEF) compared with placebo.¹ The benefit was independent of ejection fraction or diabetes status,¹ establishing empagliflozin as the only compound to significantly improve outcomes for patients with heart failure and preserved ejection fraction. The results were presented today at the European Society of Cardiology Congress 2021² and published in The New England Journal of Medicine.¹ The overall safety data was consistent with previous findings, confirming the known safety profile of empagliflozin.[iii]

Key secondary endpoint analyses showed that empagliflozin also reduced the relative risk of first and recurrent hospitalisations for heart failure by 27 percent (ARR 4.5%; HR 0.73; 95% CI: 0.61 to 0.88; p<0.001) ²⁸ and significantly slowed kidney function decline when compared to placebo (+1.36ml/min/1.73m²/year difference in eGFR (estimated Glomerular Filtration Rate) slope vs placebo; 95% CI: 1.06,1.66; p<0.001).¹

“There are currently no clinically proven treatments we can offer people living with HFpEF that can have such a positive impact on their condition or reduce their chances of being admitted to hospital for heart failure,” said Iain Squire, Professor of Cardiovascular Medicine at the University of Leicester, and Lead Investigator for EMPEROR-Preserved in the UK. “But this data from the EMPEROR-Preserved trial firmly establishes the potential for a new treatment for HFpEF patients in the UK and Ireland. The primary endpoint demonstrated benefit for patients with ejection fraction above 40% and was consistent across further subgroups, including men and women, as well as those with and without diabetes, which underlines empagliflozin’s potential for improvement in patients’ quality of life and outcomes.”  

In people aged over 65, heart failure is the most common cause of hospital admission in the UK and one of the most common causes in Ireland.[iv]^,[v] More than 60 million people worldwide have heart failure and approximately half of them have HFpEF, which is also known as diastolic heart failure.[vi]^,[vii] HFpEF has been described as the single largest unmet need in cardiovascular medicine based on prevalence, poor outcomes and the absence of clinically proven therapies to date.[viii]^,[ix]

EMPEROR-Preserved included 5,988 people with heart failure.¹ 4,005 had a left ventricular ejection fraction (LVEF) of 50 percent or above and 1,983 had a LVEF below 50 percent.¹ Trial participants were randomly assigned to empagliflozin 10 mg (n=2,997) or placebo (n=2,991) once daily.¹

“Heart failure is a complex, serious health issue, a leading cause of hospitalisation and has a big impact on patients’ quality of life,” said Dr Douglas Clark, Head of Medical Affairs for UK and Ireland at Boehringer Ingelheim. “The risk of death for people with heart failure rises with each hospital admission and with kidney function decline. The landmark EMPEROR-Preserved trial shows that empagliflozin brings significant benefit, which is welcome news for both the medical and patient communities.”

Empagliflozin is currently indicated for the treatment of adults with insufficiently controlled type 2 diabetes and for the treatment of symptomatic chronic heart failure with reduced ejection fraction.[x]^,[xi]

^[i] Anker S, Butler J, Filippatos G, et al. Empagliflozin in Heart Failure With a Preserved Ejection Fraction. N Engl J Med. 2021;10.1056/NEJMoa2107038

^[ii] Anker S. EMPEROR-Preserved: effect of empagliflozin on cardiovascular death and heart failure hospitalisations in patients with heart failure with a preserved ejection fraction, with and without diabetes. Presented on 27 August 2021 at the European Society of Cardiology (ESC) Congress 2021 – The Digital Experience

[iii] Boehringer Ingelheim. Data on file

[iv] NICE. Resource impact report: Chronic heart failure in adults: diagnosis and management (NG106. Available at: https://www.nice.org.uk/guidance/ng106/resources/resource-impact-report-pdf-6537494413. Accessed July 2020

[v] HSE. What is heart Failure? Available at: https://www.hse.ie/eng/health/hl/living/heartfailure/. Accessed July 2020

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

^[vii] 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

^[viii] 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

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

^[x] Jardiance® (empagliflozin) tablets SmPC. Available at: https://www.medicines.org.uk/emc/product/5441/smpc#gref Last updated on emc: 4 August 2021. Last accessed August 2021     

^[xi] Jardiance® 10 mg and 25 mg film-coated tablets SmPC United Kingdom (Northern Ireland), Republic of Ireland and Maltaempagliflozin. Available at: https://www.medicines.ie/medicines/jardiance-10-mg-and-25-mg-film-coated-tablets-32545/spc#spc Last accessed August 2021