DETERMINE-preserved - Dapagliflozin Effect on Exercise Capacity Using a 6-minute Walk Test in Patients With Heart Failure With Preserved Ejection Fraction

Inclusion Criteria:

- Provision of signed informed consent prior to any study specific procedures

- Male or female, aged ≥40 years

- Established documented diagnosis of symptomatic HFpEF (NYHA functional class II-IV),
which has been present for at least 8 weeks

- LVEF>40% and evidence of structural heart disease

- Elevated NT-proBNP levels

- Patients should receive background standard of care as described below: All patients
will be treated according to locally recognised guidelines on standard of care
treatment for patients with HFpEF. Therapy should have been individually optimised and
stable for ≥4 weeks (this does not apply to diuretics) and include (unless
contraindicated or not tolerated) treatment of co morbidities (including high blood
pressure, ischaemic heart disease, atrial fibrillation).

- 6MWD≥100 metres and ≤425 metres at enrolment and randomization

Exclusion Criteria:

- Presence of any condition that precludes exercise testing

- Participation in a structured exercise training programme in the 1 month prior to
screening or planned to start during the trial

- Receiving therapy with an SGLT2 inhibitor within 4 weeks prior to enrolment or
previous intolerance of an SGLT2 inhibitor

- Type 1 diabetes mellitus

- eGFR <25 mL/min/1.73 m2 (CKD-EPI formula) at enrolment, unstable or rapidly
progressing renal disease at time of randomisation

- Systolic BP <95 mmHg on 2 consecutive measurements

- Systolic BP ≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications
or ≥180 mmHg irrespective of treatments, on 2 consecutive measurements

- Current acute decompensated HF or hospitalisation due to decompensated HF <4 weeks
prior to enrolment

- MI, unstable angina, coronary revascularization ablation of atrial
flutter/fibrillation, valve repair/replacement, implantation of a cardiac
resynchronization therapy device within 12 weeks prior to enrolment or planned to
undergo any of these operations after randomization.

- Stroke or transient ischemic attack within 12 weeks prior to enrolment.

- Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease
including COPD.

- Previous cardiac transplantation or implantation of a ventricular assistance device or
similar device, or implantation expected after randomization

- HF due to infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis,
cardiac tamponade, known genetic hypertrophic cardiomyopathy or obstructive
hypertrophic cardiomyopathy, arrhythmogenic right ventricular
cardiomyopathy/dysplasia, or uncorrected primary valvular disease