Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure.

This is an international, multicentre, parallel-group, event-driven, randomised, double-blind
study in patients with HFpEF, evaluating the effect of dapagliflozin 10 mg versus placebo,
given once daily in addition to background regional standard of care therapy, including
treatments to control co-morbidities, in reducing the composite of CV death and heart failure
events (hospitalisations for HF or urgent HF visits). Adult patients aged ≥40 years with
HFpEF (LVEF >40% and evidence of structural heart disease) and New York Heart Association
(NYHA) class II-IV who are eligible according to the inclusion/exclusion criteria will be
randomised in a 1:1 ratio to receive either dapagliflozin 10 mg or placebo. Both out-patients
and in-patients hospitalised for heart failure and off intravenous heart failure-therapy for
24 hours can be randomised. It is estimated that approximately 8000 patients at 400-500 sites
in 20-25 countries will need to be enrolled to reach the target of approximately 4700
randomised patients.

Inclusion Criteria:

1. Provision of signed informed consent prior to any study specific procedures.

2. Male or female patients age ≥40 years.

3. 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.

4. Left Ventricular Ejection Fraction (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 MR 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 6, qualifying cardiac imaging assessment
at least 12 weeks following the procedure/event is required.

5. Elevated NT-pro BNP levels.

6. Both ambulatory and hospitalised patients may be enrolled and randomised. Patients
currently hospitalised for HF, must be off intravenous HF medications for at least 24
before randomisation.

Further details regarding inclusion criteria 4-6 may apply.

Exclusion Criteria:

1. Receiving therapy with an SGLT2 inhibitor within 4 weeks prior to randomisation or
previous intolerance to an SGLT2 inhibitor.

2. Type 1 diabetes mellitus (T1D).

3. eGFR <25 mL/min/1.73 m2 (CKD-EPI formula) at Visit 1.

4. Systolic blood pressure (BP) <95 mmHg on 2 consecutive measurements at 5-minute
intervals, at Visit 1 or at Visit 2.

5. Systolic BP≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications
or ≥180 mmHg irrespective of treatments, on 2 consecutive measurements at 5-minute
intervals, at Visit 1 or at Visit 2.

6. MI, unstable angina, coronary revascularization (percutaneous coronary intervention
(PCI) or coronary artery bypass grafting (CABG)), 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 MRI examination at least 12 weeks after the event.

7. Planned coronary revascularization, ablation of atrial flutter/fibrillation and valve
repair/replacement.

8. Stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment.

9. Probable alternative or concomitant diagnoses which in the opinion of the investigator
could account for the patient's HF symptoms and signs (e.g. anaemia, hypothyroidism).

10. Body mass index >50 kg/m2.

Further exclusion criteria may apply