Empagliflozin (Jardiance®) approved by MHRA as UK’s first effective treatment for symptomatic chronic heart failure regardless of ejection fraction

Bracknell, UK, 14 June 2022 – The Medicines and Healthcare Products Regulatory Agency (MHRA) has granted marketing authorisation for the use of empagliflozin (Jardiance^®) as a treatment for adults with symptomatic chronic heart failure.[i] This breakthrough approval expands the existing indication of empagliflozin to include adults with heart failure with preserved ejection fraction (HFpEF), an underserved patient population who previously had no licensed and clinically proven therapies. SGLT2 inhibitor empagliflozin was previously approved for the treatment of adults with symptomatic chronic heart failure with reduced ejection fraction (HFrEF). With this authorisation, it becomes the first and only licensed treatment to significantly improve outcomes for adult patients with symptomatic chronic heart failure, regardless of ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) occurs when the left ventricle of the heart is unable to relax and properly fill with blood, resulting in less blood being available to be pumped out to the body. It is defined by an ejection fraction above 50%. Heart failure with reduced ejection fraction (HFrEF) is an ejection fraction below 40%, when the left ventricle of the heart is not able to contract effectively, therefore the heart cannot pump with enough force.[ii]^,[iii] Approximately half of all heart failure patients have HFpEF, which has been described as the single largest unmet need in cardiovascular medicine, based on prevalence, poor outcomes and the absence of effective treatment options.[iv]^,[v],[vi] Empagliflozin significantly improves outcomes regardless of ejection fraction, with clinical trial data demonstrating its effect on reducing the combined relative risk of cardiovascular death or hospitalisation for heart failure.[vii]^,[viii]

Professor Simon Williams, Past Chair of The British Society for Heart Failure, the professional association for heart failure care in the UK, commented: “Until now there were no approved treatments that can improve outcomes or reduce the likelihood of heart failure hospitalisations for patients across the full spectrum of heart failure, including HFpEF. The expanded approval of empagliflozin by the MHRA marks a turning point in the management of heart failure and has the potential to change clinical practice for the thousands of people in the UK affected by this debilitating and life-limiting condition.”

The MHRA authorisation was based on results from the landmark EMPEROR-Preserved Phase III clinical trial, the first of its kind to significantly show a relative reduction in the primary composite endpoint of cardiovascular death or hospitalisation for heart failure in adults with HFpEF, treated with empagliflozin compared to placebo, both added to standard of care. Results demonstrated a 21% relative risk reduction in the composite primary endpoint, occurring in 415 patients (13.8%) in the empagliflozin group and in 511 patients (17.1%) in the placebo group (hazard ratio 0.79, 95% confidence interval 0.69-0.90; P<0.001), 3.3% absolute risk reduction.⁷

Dr Douglas Clark, Head of Medical Affairs at Boehringer Ingelheim UK & Ireland added: “Heart failure is a serious and challenging disease to treat. Around a half of all cases are HFpEF, which for too long had a lack of approved and effective treatments. The Boehringer Ingelheim and Lilly Alliance aims to bring innovation to patients with cardio-renal-metabolic disease and advance the treatment of heart failure. We hope the approval of empagliflozin will be transformative for clinicians and those living with this severe, long term condition.”

Heart failure affects an estimated 920,000 people in the UK.[ix] People experience breathlessness and fatigue, which can severely impact their quality of life.[x] It is one of the leading causes of avoidable hospitalisations, associated with considerable NHS resource utilisation and a detrimental impact on patients’ quality of life and life expectancy.[xi]

“This approval is a genuine watershed moment and positive news because for the first time there is a beneficial treatment approved for people with heart failure with preserved ejection fraction,” said Nick Hartshorne-Evans, CEO of the Pumping Marvellous Foundation, the leading heart failure patient organisation. “Heart failure is progressive and if not effectively treated has a higher mortality than common cancers. Symptoms of breathlessness, tiredness and fluid build-up within the body have a hugely detrimental impact on people’s quality of life. It is essential that those living with heart failure have effective treatment options to address the significant impact it has on their daily lives.”

[i] Medicines & Healthcare products Regulatory Agency https://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency

[ii] Savarese G et al. Heart failure with mid-range or mildly reduced ejection fraction. Nat Rev Cardiol. 2022;19(2):100–116.

^[iii] American Heart Association. Ejection Fraction Heart Failure Measurement. Available at: https://www.heart.org/en/health-topics/heart-failure/diagnosing-heart-failure/ejection-fraction-heart-failure-measurement. Accessed: March 2022.

[iv] Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection fraction. Nature Reviews Cardiology.2017;14:591-602.

[v] 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.

[vi] Bhatt D et al. EMPEROR-Preserved: A promise fulfilled. Cell Metab. 2021;Nov 2;33(11):2099-2103.

[vii] Anker SD, Butler J, Filippatos JP et al. Empagliflozin in heart failure patients with a preserved ejection fraction. NEJM. 2021 October;385(16):1451-1461.

[viii] Packer M, Butler J, Filippatos G, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383:1413-1424.

[ix] British Heart Foundation UK Factsheet. July 2021. Available at: https://www.bhf.org.uk/what-we-do/our-research/heart-statistics. Accessed: March 2022.

[x] APPG on heart disease. Focus on heart failure report. https://www.bhf.org.uk/informationsupport/publications/focus-on-heart-failure-appg-report Accessed: March 2022.

[xi] British Heart Foundation. Heart failure: A Blueprint for Change. Available at:

https://www.bhf.org.uk/-/media/files/health-intelligence/heart-failure-a-blueprint-for-change.pdf?la=en&rev=f89dedb7c933452e8086cc063ff98c26&hash=98E3BEADD6A46974EF0AAD86044B8DC5314F4E2B. Accessed: March 2022.