Title: Dapagliflozin for treating chronic heart failure with preserved or mildly reduced ejection fraction [ID1648]
Funder: Department of Health and Social Care

Abstract: Heart failure is a complex clinical syndrome of signs and symptoms, generally defined as the inability of the heart to supply sufficient blood flow to meet the body's needs. It is caused by structural or functional abnormalities of the heart, commonly resulting from coronary artery disease. Other conditions that can increase the risk of heart failure include; ischaemic heart disease, atrial fibrillation, valve disease, hypertension, diabetes, chronic obstructive pulmonary disease, and asthma.[1] The European Society of Cardiology (ESC) defines 3 types of chronic heart failure based on left ventricular ejection fraction (LVEF), a measurement of how much blood the left ventricle pumps out with each contraction. The ESC defines heart failure with reduced ejection fraction as a LVEF of 40% or less; mildly reduced ejection fraction as a LVEF between 41% and 49%; and preserved ejection fraction as a LVEF of 50% or more. [2] NICE guideline 106 for chronic heart failure in adults (NG106) states that heart failure with preserved ejection fraction is usually associated with impaired left ventricular relaxation, rather than left ventricular contraction, and is characterised by normal or preserved LVEF with evidence of diastolic dysfunction. Symptoms of heart failure commonly include breathlessness, fatigue and ankle swelling. Quality of life is affected by the physical limitations imposed by the symptoms. _x000D_ _x000D_ More than 550,000 people in England have heart failure and around 50% have preserved or mildly reduced ventricular ejection fraction. [2],[3] There were 94,185 hospitalisations in England for heart failure in 2019/20. [4] Both the prevalence and incidence of heart failure increase with age. Around 24% of people diagnosed with heart failure die within the first year, with a 5-year mortality rate of about 55%. [5] _x000D_ _x000D_ NG106 recommends low to medium dose loop diuretics for people with chronic heart failure with preserved ejection fraction. Specialist advice is needed if the disease does not respond. Most people with chronic heart failure with preserved ejection fraction also have symptomatic treatments for comorbidities, including angiotensinconverting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), betablockers or mineralocorticoid receptor antagonists (MRAs).[2]_x000D_ _x000D_ References_x000D_ 1. National Institute for Cardiovascular Outcomes Research (2019) National heart failure audit 2017/18. Available at: https://www.hqip.org.uk/wp- content/uploads/2019/09/Ref-129-Cardiac-Heart-Failure-Summary-Report2019-FINAL.pdf. Accessed November 2021._x000D_ 2. McDonagh, Theresa A., et al. (2021) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal 42.36: 3599-3726._x000D_ 3. NHS Digital (2021) Quality and Outcomes Framework, 2020-21. Prevalence at regional and national level. Available at: https://digital.nhs.uk/data-andinformation/publications/statistical/quality-and-outcomes-frameworkachievement-prevalence-and-exceptions-data/2020-21. Accessed March 2022._x000D_ 4. NHS Digital (2020) Hospital admitted patient care activity, 2019-20: Primary diagnosis 3 character. Available at: https://digital.nhs.uk/data-andinformation/publications/statistical/hospital-admitted-patient-careactivity/2019-20. Accessed March 2022._x000D_ 5. Taylor CJ, Ordonez-Mena JM, Roalfe AK et al. (2019) Trends in survival after a diagnosis of heart failure in the United Kingdom 2000-2017: population based cohort study. BMJ 364:l223.

Lay abstract: To appraise the clinical and cost effectiveness of dapagliflozin within its marketing authorisation for treating symptomatic chronic heart failure with a left ventricular ejection fraction of 40% or more.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR