Dapagliflozin Effects on Cardiometabolic Outcomes in Patients With an Acute Heart Attack.

A Registry-based, Randomised, Double-blind, Placebo-Controlled Cardiovascular Outcomes Trial to Evaluate the Effect of Dapagliflozin on Cardiometabolic Outcomes in Patients Without Diabetes With Acute Myocardial Infarction at Increased Risk for Subsequent Development of Heart Failure

This study will evaluate the effect of dapagliflozin versus placebo, given once daily in addition to Standard of Care (SoC) therapies for patients with myocardial infarction (MI), for hospitalisation for heart failure (HHF), cardiovascular (CV) death, and other cardiometabolic outcomes.

This is a multicentre, parallel group double-blind, placebo-controlled phase 3 registry-based randomised controlled trial (R-RCT) in patients without diabetes presenting with myocardial infarction (MI) (ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI)) and evidence of impaired regional or global LV systolic function or definite evidence of Q wave MI on ECG. In the study the effect of dapagliflozin versus placebo, given once daily in addition to SoC therapy will be evaluated for the hospitalisation for HF, CV death, and other cardiometabolic outcomes.

Inclusion Criteria:

• Participant must be ≥18 at the time of signing the informed consent
• Confirmed MI, either STEMI or NSTEMI, according to the fourth universal definition of MI (Thygesen et al 2019), within the preceding 7 days, or 10 days if earlier randomisation is not feasible
• Evidence of impaired regional or global LV systolic function at any timepoint during current MI-related hospitalisation (established with echocardiogram, radionuclide ventriculogram, contrast angiography or cardiac MRI) or definitive evidence on ECG of Q wave MI (defined as presence of Q waves in two or more contiguous leads, excluding leads III and aVR, and meeting all the following criteria: at least 1.5 mm in depth; at least 30 ms in duration; and, if R wave present, more than 25% of the size of the subsequent R wave)
• Hemodynamically stable at randomization (no episodes of symptomatic hypotension, or arrhythmia with haemodynamic compromise in the last 24 hours).
• Male or female
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol
• Provision of signed and dated, written informed consent prior to any mandatory study specific procedures, sampling, and analyses

Exclusion Criteria:

• Known type 1 diabetes mellitus (T1DM) or T2DM at the time for admission. Patients with hyperglycaemia, but without a diagnosis of diabetes mellitus prior to the index event, are eligible at the discretion of the Investigator. Patients who present with signs and symptoms consistent with ketoacidosis, including nausea, vomiting, abdominal pain, malaise and shortness of breath should be assessed for ketoacidosis, and if ketoacidosis is confirmed the patient should not be randomized.
• Chronic symptomatic HF with a prior HHF within the last year and known reduced ejection fraction (LVEF≤40 %), documented before the current MI hospitalization
• Severe (eGFR <20 mL/min/1.73 m2 by local laboratory), unstable or rapidly progressing renal disease at the time of randomization
• Severe hepatic impairment (Child-Pugh class C) at the time of inclusion into the trial
• Active malignancy requiring treatment at the time of screening, except for basal cell- or squamous cell carcinoma of the skin, presumed possible to treat successfully
• Any non-CV condition, eg malignancy, with a life expectancy of less than two years based on the investigator´s clinical judgement
• Currently on treatment, or with an indication for treatment, with a sodium glucose co-transporter 2 inhibitor (SGLT2-inhibitor)