• Today’s choice from the Medicines and Healthcare merchandise Regulatory Agency (MHRA) marks the approval of dapagliflozin for the remedy of symptomatic power coronary heart failure (HF) and left ventricular ejection fraction (LVEF) >40%, together with HF with mildly lowered ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF).1
• This choice is predicated on constructive knowledge from the DELIVER Phase III trial which confirmed that dapagliflozin lowered the composite end result of cardiovascular (CV) dying or worsening of HF by 18% vs placebo.2
• HF impacts virtually a million folks within the UK, with roughly 270,000 undiagnosed.3
• Following this choice from the MHRA, an extra 250,000 sufferers may now be eligible for remedy in England and Wales.4,5,6
London, UK, Monday 12 December 2022 – AstraZeneca as we speak introduced that the Medicines and Healthcare merchandise Regulatory Agency (MHRA) has granted a licence extension for dapagliflozin in Great Britain for the remedy of symptomatic power coronary heart failure (HF) in sufferers with HF and a left ventricular ejection fraction (LVEF) >40%, together with HF with mildly lowered ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF). This choice signifies that dapagliflozin is now permitted for sufferers with symptomatic power HF throughout the total spectrum of left ventricular ejection fraction (LVEF), together with HF with lowered, mildly lowered, and preserved ejection fraction (HFrEF, HFmrEF, HFpEF).1
HF is a life-threatening power illness wherein the center can’t pump sufficient blood across the physique, affecting virtually a million folks within the UK, with roughly 270,000 dwelling with the situation undiagnosed.3,7 There are three major classes of HF associated to ejection fraction (EF), a measurement of the proportion of blood leaving the center every time it contracts, together with: HFrEF (LVEF lower than or equal to 40%), HFmrEF (LVEF 41-49%) and HFpEF (LVEF higher than or equal to 50%).7 Approximately 59% of all HF sufferers have mildly lowered or preserved EF with few therapeutic choices obtainable.4 Dapagliflozin is already permitted in Great Britain for the remedy of insufficiently managed sort 2 diabetes (T2D), symptomatic power HFrEF and power kidney illness (CKD).1
John McMurray, MD, Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK, stated: “Today’s approval from the MHRA is a significant moment for patients living with heart failure in Great Britain, particularly for those with a preserved ejection fraction, who until now, have had few treatment options. Dapagliflozin has been clinically shown to reduce hospitalisations and cardiovascular deaths in heart failure and as a clinician, I’m pleased to see this decision that will bring us closer to addressing the full spectrum of heart failure and reducing the significant disease burden in Great Britain.”
The choice from the MHRA was primarily based on outcomes from the DELIVER Phase III trial, which confirmed that dapagliflozin met its main endpoint in decreasing the composite end result of cardiovascular (CV) dying or worsening HF by 18% (16.4% within the dapagliflozin group and 19.5% within the placebo group over a median follow-up of two.3 years [hazard ratio {HR} =0.82 {95% CI 0.73-0.92}; p<0.001, ARR 3.1%]). The remedy impact was constant throughout the LVEF vary, with out proof of attenuation of impact by LVEF.2
Additionally, the pre-specified, affected person stage, pooled evaluation of the DELIVER and DAPA-HF Phase III trials demonstrated that dapagliflozin lowered the chance of CV dying by 14% (HR = 0.86 [95% CI 0.76-0.97]; p=0.01, ARR 1.5%) over the median follow-up of twenty-two months, dying from any trigger by 10% (HR = 0.90 [95% CI 0.82-0.99]; p=0.03, ARR 1.5%), complete (first and repeat) hospitalisation for HF by 29% (charge ratio [RR] = 0.71 [95% CI 0.65-0.78]; p<0.001, ARR 6%) and the composite of dying from CV causes, myocardial infarction, or stroke by 10% (HR = 0.90 [95% CI 0.81-1.00]; p=0.045, ARR 1.3%) in sufferers with HF no matter LVEF.8
Ed Piper, Medical and Scientific Affairs Director, AstraZeneca UK, stated: “We’re delighted that the MHRA has authorised dapagliflozin for use in heart failure with preserved ejection fraction. We continue to work with NICE and the SMC to ensure that patients living with heart failure can access dapagliflozin as quickly as possible. Today’s milestone demonstrates AstraZeneca’s commitment to deliver effective medicines that improve outcomes for patients across the full spectrum of heart failure.”
In the DELIVER Phase III trial, knowledge was solely collected on critical adversarial occasions (AEs) that led to discontinuation of dapagliflozin or placebo and different choose AEs, because of the in depth security knowledge on dapagliflozin and established security profile. Overall, critical AEs, together with dying, have been reported in 43.5% of sufferers (n=1361) within the dapagliflozin group and in 45.5% of sufferers (n=1423) within the placebo group. AEs that led to discontinuation of dapagliflozin or placebo have been reported in 5.8% of sufferers (n=182) within the dapagliflozin group and in 5.8% of sufferers (n=181) within the placebo group.2
References
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2. Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022;387:1089-1098.
3. British Heart Foundation. UK Factsheet. Available at: https://d1qotm6w854ck0.cloudfront.net/Uploads/a/f/a/bhfcvdstatisticsukfactsheet1_343908.pdf. Last accessed: December 2022.
4. AstraZeneca UK Ltd. Data on File. ID:REF-155912 July 2022.
5. Office for National Statistics (ONS). Mid-Year Population Estimates, UK, June 2020. Available at: https://www.ons.gov.uk/file?uri=/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland/mid2020/ukpopestimatesmid2020on2021geography.xls. Last accessed December 2022.
6. NHS Digital. Quality and Outcomes Framework 2020-21. Available at: https://files.digital.nhs.uk/E7/790861/qof-2021-prev-ach-pca-reg-nat-v2.xlsx . Last accessed December 2022.
7. Dunlay SM, et al. Epidemiology of coronary heart failure with preserved ejection fraction. Nat Rev Cardiol. 2017;14:591–602.
8. Jhund, P.S., Kondo, T., Butt, J.H. et al. Dapagliflozin throughout the vary of ejection fraction in sufferers with coronary heart failure: a patient-level, pooled meta-analysis of DAPA-HF and DELIVER. Nat Med. 2022;28:1956-1964.