The purpose of this study is to evaluate the effect of dapagliflozin on the incidence of worsening heart failure or cardiovascular death in patients with chronic heart failure with reduced ejection fraction

This is an international, multicentre, parallel group, event-driven, randomized, double-blind, placebo-controlled study in patients with chronic heart failure with reduced ejection fraction (HFrEF), evaluating the effect of dapagliflozin versus placebo, given once daily in addition to background regional standard of care therapy, for the prevention of cardiovascular (CV) death or reduction of heart failure (HF) events.

Inclusion Criteria:

• Provision of signed informed consent prior to any study specific procedures
• Male or female, aged ≥18 years
• Established documented diagnosis of symptomatic HFrEF (NYHA functional class II-IV), which has been present for at least 2 months
• LVEF≤40%
• Elevated NT-proBNP levels
• Patients should receive background standard of care for HFrEF and be treated according to locally recognized guidelines
• eGFR ≥30 mL/min/1.73 m^2 (CKD-EPI formula) at enrolment (visit 1)

Exclusion Criteria:

• Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
• Type 1 diabetes mellitus
• Symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements either at visit 1 or visit 2
• Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment
• MI, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrolment
• Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or valvular repair/replacement within 12 weeks prior to enrolment or planned to undergo any of these operations after randomization
• Implantation of a CRT within 12 weeks prior to enrolment or intent to implant a CRT device
• Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after randomization
• HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease
• Symptomatic bradycardia or second or third degree heart block without a pacemaker
• Severe (eGFR <30 mL/min/1.73 m^2 by CKD-EPI), unstable or rapidly progressing renal disease at the time of randomization