Table 1.

Eligibility criteria for DELIVER

Inclusion criteria

Ability to give written informed consent. Men and women age ≥40 years. Documented diagnosis of symptomatic heart failure (NYHA class II–IV) at enrolment, and a medical history of typical symptoms/signs of heart failure ≥6 weeks before enrolment with at least intermittent need for diuretic treatment (requiring recurrent intermittent dosing). LVEF >40% and evidence of structural heart disease (i.e. left ventricular hypertrophy or left atrial enlargement) documented by the most recent echocardiogram, and/or cardiac magnetic resonance within the last 12 months prior to enrolment. For patients with prior acute cardiac events or procedures that may reduce LVEF, e.g. as defined in exclusion criterion, qualifying cardiac imaging assessment at least 12 weeks following the procedure/event is required. Structural heart disease will be defined as: LA enlargement with at least one of the following: LA width (diameter) ≥3.8 cm or LA length ≥ 5.0 cm, or LA area ≥20 cm, or LA volume ≥55 mL or LA volume index ≥29 mL/m. Left ventricular hypertrophy with septal thickness or posterior wall thickness ≥ 1.1 cm. NT‐proBNP ≥300 pg/mL at Visit 1 for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at Visit 1, NT‐proBNP must be ≥600 pg/mL. Patients may be ambulatory, or hospitalized; patients must be off intravenous heart failure therapy (including diuretics) for at least 12 h prior to enrolment and 24 h prior to randomization.

Exclusion criteria

Receiving therapy with an SGLT2 inhibitor within 4 weeks prior to randomization or previous intolerance to an SGLT2 inhibitor. Type 1 diabetes mellitus. eGFR < 25 mL/min/1.73 m2 (CKD‐EPI formula) at Visit 1. Systolic blood pressure <95 mmHg on two consecutive measurements at 5 min intervals, at Visit 1 or at Visit 2. Systolic blood pressure ≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications or ≥180 mmHg irrespective of treatments, on two consecutive measurements at 5 min intervals, at Visit 1 or at Visit 2. Myocardial infarction, unstable angina, coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), ablation of atrial flutter/fibrillation, valve repair/replacement within 12 weeks prior to enrolment. Before enrolment, these patients must have their qualifying echocardiography and/or cardiac magnetic resonance examination at least 12 weeks after the event. Planned coronary revascularization, ablation of atrial flutter/fibrillation and valve repair/replacement. Stroke or transient ischaemic attack within 12 weeks prior to enrolment. Probable alternative or concomitant diagnoses which in the opinion of the investigator could account for the patient's heart failure symptoms and signs (e.g. anaemia, hypothyroidism). Body mass index >50 kg/m2. Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD (i.e. requiring home oxygen, chronic nebulizer therapy or chronic oral steroid therapy, or hospitalization for exacerbation of COPD requiring ventilatory assistance within 12 months prior to enrolment). Previous cardiac transplantation, or complex congenital heart disease. Planned cardiac resynchronization therapy. Heart failure due to any of the following: known infiltrative cardiomyopathy (e.g. amyloid, sarcoid, lymphoma, endomyocardial fibrosis), active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia, or uncorrected primary valvular disease. A life expectancy of less than 2 years due to any non‐cardiovascular condition, based on investigator's clinical judgement. Inability of the patient, in the opinion of the investigator, to understand and/or comply with study medications, procedures and/or follow‐up or any conditions that, in the opinion of the investigator, may render the patient unable to complete the study. Active malignancy requiring treatment (with the exception of basal cell or squamous cell carcinomas of the skin). Acute or chronic liver disease with severe impairment of liver function (e.g. ascites, oesophageal varices, coagulopathy). Women of child‐bearing potential (i.e. those who are not chemically or surgically sterilized or post‐menopausal) not willing to use a medically accepted method of contraception considered reliable in the judgement of the investigator or who have a positive pregnancy test at randomisation or who are breast‐feeding. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca personnel and/or personnel at the study site). Previous randomization in the present study. Participation in another clinical study with an investigational product or device during the last month prior to enrolment.

CKD‐EPI, Chronic Kidney Disease Epidemiology Collaboration; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; LA, left atrial; LVEF, left ventricular ejection fraction; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; NYHA, New York Heart Association; SGLT2, sodium–glucose co‐transporter 2.