Type 2 diabetes mellitus (T2DM) is one of the most important risk factors for atherosclerotic heart disease. Strategies focused solely on glycemic control have failed to demonstrate vascular events reduction in this population. On the other hand, new antidiabetic drugs recently have demonstrated significant decrease of cardiovascular mortality, raising the hypothesis that possible effects beyond glycemia control could explain this benefit. Aim: This study is intended to evaluate possible pleiothropic effects of dapaglifozin, a SGLT-2 (sodium glucose cotransporter 2) inhibitor, in individuals admitted with a diagnosis of Acute Myocardial Infarction (AMI). Methods: This is a prospective, randomized, double-blind, placebo controlled trial. Individuals presenting with AMI whithin the first seven days of evolution will be randomized to dapaglifozin or placebo. The investigators's goal is to analyze platelet aggregability 48 hours after randomization (primary endpoint), as well as glycemic control, cardiac biomarkers, corrected QT interval electrocardiographic analysis, autonomic modulation through spectral analysis of the RR interval and inflammatory biomarkers at inclusion and 30 days after starting study drug (secondary endpoints). Sample size calculation resulted in 80 individuals (40 per group). Expected results: This study will seek to aggregate new insights to the current knowledge about this new antidiabetic drug class. Previous randomized clinical trials have demonstrated that SGLT-2 inhibitors significantly reduced the composite endpoint of cardiovascular death, AMI or stroke, as well as Heart Failure (HF) hospitalization. Therefore, this study is supposed to clarify possible mechanisms that could explain these results aforementioned.

Study design: Single-center, prospective, randomized, double-blind, placebo-controlled, parallel-group clinical study.

Primary Outcome: To compare platelet aggregation in the dapagliflozin and placebo groups by the Multiplate Analyzer® test (using ADP as an agonist) in hospitalized patients with a diagnosis of AMI within seven days of evolution, using dual antiplatelet therapy with acetylsalicylic acid (ASA) and an anti-platelet ADP, 48 ± 12 hours after starting dapagliflozin/placebo treatment. Due to the rapid oral absorption of the medication, reaching maximum plasma concentration after 2 hours and as its pharmacokinetics does not change with food or other concomitant medications, our hypothesis is that there may be an antiplatelet effect that can be detected early

Other exploratory analyses:

1. compare B-type natriuretic peptide (BNP) and troponin biomarkers between dapagliflozin and placebo groups at 30 (± 5) days after randomization;
2. Correlation between levels of ultrasensitive C-reactive protein (us-CRP) and platelet aggregability;
3. Compare hsCRP levels in dapagliflozin and placebo groups at 30 (± 5) days;
4. Compare the size of the AMI assessed by peak CK-MB mass and troponin in the dapagliflozin and placebo groups;
5. Compare the behavior of glycemia in the dapagliflozin and placebo groups, taking into account the following parameters: calculation of the glycemic mean (±SD) of capillary blood glucose tests (remote laboratory tests) during 48 hours after randomization; incidence of hypoglycemia (blood glucose below 70 mg/dl) and severe hypoglycemia (glycemia below 40 mg/dl) during hospitalization; calculation of the average insulin used during 48 hours after randomization;
6. Compare, in the dapagliflozin and placebo groups, the levels of creatinine, urea and hematocrit analyzed immediately after randomization and before starting treatment, and 30 (± 5) days after randomization;
7. Test of lipid transfer from artificial nanoemulsion to HDL in dapagliflozin and placebo groups at inclusion and at 30 (± 5) days after randomization: EDTA plasma samples in a volume of 200 μL will be incubated with 50 μL nanoemulsion artificial in 3H-cholesteryl-esters and 14C-phospholipids or with free 14C-cholesterol and 3H-triglycerides. After 1h in agitation of the bath at 37 ºC, the precipitation reagent consisting of 250 μL of the solution with 0.02% dextran sulfate (50,000 MW) and 0.3 mol / L of MgCl2 will be added to the incubation, which will then be mixed for 30 seconds and centrifuged for 10 min (3000g). Finally, 250 μL of the supernatant is transferred to counting vials containing 5 μL of scintillation solution (Packard BioScience, Groeningen, The Netherlands) and the radioactivity measured with a Packard model TR 1600 liquid scintillation analyzer (Palo Alto, CA). Blank plasma samples will be replaced by 200 μL of TRIS solution. The radioactive transfer results from the nanoemulsion to HDL will be expressed as % of the total incubated radioactivity found in the supernatant containing HDL.
8. Compare the diuresis obtained during 48 hours after randomization in the Coronary Intensive Care Unit, in the dapagliflozin and placebo groups.
9. Compare, in the dapagliflozin and placebo groups, autonomic modulation, vascular autonomic control and assessment of baroreflex control by means of a 10-minute electrocardiogram, after inclusion and before the start of treatment, and 30 (± 5) days after randomization .

Analyze the primary objective of the study in the following pre-specified subgroups:

1. obese (BMI ≥ 30 Kg/m2) and non-obese;
2. male and female sex;
3. elderly (≥ 65 years) and non-elderly;
4. smokers and non-smokers;
5. time since diagnosis of diabetes (≥ or < 10 years);
6. basal blood glucose ≥ 125 mg/dL and < 125 mg/dL;
7. glycated hemoglobin (HbA1c) ≤ 9.0% and > 9.0%;
8. use of clopidogrel or ticagrelor;
9. treatment performed for the acute coronary event: percutaneous coronary intervention or clinical treatment;
10. ejection fraction ≤ 40% and > 40%.
11. Diabetics and non-diabetics
12. Onset of symptoms ≤ 72 hours and > 72 hours

Study plan: Eligible patients will be enrolled within the first seven days of symptom onset. After signing the Informed Consent Form, laboratory tests will be collected, as previously specified in the methodology. Subsequently, patients will be randomized to use dapagliflozin or placebo in a double-blind manner. Randomization will be performed using the Graphipad® program, with distribution of numbered vials containing the study medication (dapagliflozin 10 mg tablets or placebo-equivalent), randomly between the two groups. All patients must be using dual antiplatelet therapy and the results will be stratified by the type of treatment performed for AMI. Study medication, once initiated, will be maintained until the final platelet assessment, scheduled for 30 days, is performed. The other medications, including other oral antidiabetics and insulin, will be used according to the institution's routines, except for prohibited medications, as stated in the exclusion criteria. After the end of the study, the sealed envelopes will be opened to identify the blinding codes.

Glycemic control: According to institutional routines, the cut-off value of 140 mg/dL will be used in two sequential capillary blood glucose levels as the threshold for starting treatment with subcutaneous insulin. Patients whose diabetes control is not adequate, as evidenced by a capillary blood glucose value maintained greater than 250 mg/dL, will receive the intravenous insulin protocol, also in accordance with the institutional routines (summary below).The HbA1c target will be of < 7.5%.

Inclusion criteria:

1. Men and women aged ≥ 18 years (women of childbearing age must have a negative pregnancy test)
2. In routine use of dual antiplatelet therapy with ASA plus an ADP receptor antagonist, according to institutional routines;
3. Acute myocardial infarction, with or without ST-segment elevation (STEMI/NSTEMI) defined according to the 4th Universal Definition of Acute Myocardial Infarction, with up to 7 days of evolution from the onset of symptoms;
4. Signature of the Free and Informed Consent Term.

Exclusion criteria:

1. Current or recent (within 24 months) treatment with pioglitazone and/or use of pioglitazone for a total of 2 years or more during a lifetime at any time;
2. Current or recent (within 12 months) treatment with rosiglitazone;
3. Chronic use (>15 consecutive days) of any SGLT2 inhibitor at the time of hospitalization;
4. Chronic use (>30 consecutive days) with an oral steroid at a dose equivalent to prednisolone ≥10 mg (eg, betamethasone ≥1.2 mg, dexamethasone ≥1.5 mg, hydrocortisone ≥40 mg) per day;
5. systolic BP > 180 or diastolic BP > 100 mmHg at randomization;
6. Diagnosis of Type 1 diabetes mellitus, MODY (maturity onset diabetes of the Young) or diabetes mellitus secondary to diverse endocrinopathy, pancreatic resection, medication, pancreas neoplasia or chronic pancreatitis;
7. History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time;
8. History of any other malignancy within 5 years (with the exception of skin cancers successfully treated non-melanoma);
9. Chronic cystitis and/or recurrent urinary tract infections (3 or more in the last year);
10. Any condition that, in the opinion of the Investigator, may render the research participant unfit to complete the study, including, but not limited to, cardiovascular disease (KILLIP > 2, modified Forester > IIa,recurrent ventricular arrhythmias) or non cardiovascular (eg, active malignancy other than basal cell carcinoma, cirrhosis, chronic lung disease, severe autoimmune disease);
11. Pregnancy or lactation;
12. Active participation in another clinical trial
13. Patients with septic shock or severe glycemic decompensation requiring the use of IV insulin at the time of randomization;
14. TGP/ALT(Alanine Amino Transferase) >3x the upper limit of normality (ULN) or total bilirubin >2.5 x ULN;
15. Estimated glomerular filtration rate (GFR) < 45 ml/min/1.73m² , calculated by MDRD, or kidney transplant;
16. Known thrombophilias or thrombocytosis;
17. Blood dyscrasias or any disorder that causes hemolysis, previously known;
18. Hematological abnormality (Hb ≤ 11g/dL or > 17g/dL, leukocytes ≤ 4500/mm³ or >11000/mm³, platelet count <150,000/mm³ or > 450,000/mm³)

Casuistry: To calculate the sample size, the following assumptions were taken into account consideration :

1. Aggregability of 482.61 ± 231.82 (area under the curve AUC) in a previous study of patients with ACS using dual antiaggregation therapy with AAS and clopidogrel;
2. estimated difference of 33% less in the dapagliflozin group (323.35 ± 231.82 AUC);
3. alpha of 0.05 and statistical power of 80%. Based on this information, the sample size was calculated at 70 patients, and in order to compensate for any follow-up losses, 80 patients (40 in each group) will be included in this project.

Inclusion Criteria:

• Men and women aged ≥ 18 years (women of childbearing age must have a negative pregnancy test);
• In routine use of dual antiplatelet therapy with ASA plus an ADP receptor antagonist, according to institutional routines;
• Acute myocardial infarction, with or without ST-segment elevation (STEMI/NSTEMI) defined according to the 4th Universal Definition of Acute Myocardial Infarction, with up to 7 days of evolution from the onset of symptoms;
• Signature of the Free and Informed Consent Term.

Exclusion criteria:

• Current or recent (within 24 months) treatment with pioglitazone and/or use of pioglitazone for a total of 2 years or more during a lifetime at any time;
• Current or recent (within 12 months) treatment with rosiglitazone;
• Chronic use (>15 consecutive days) of any SGLT2 inhibitor at the time of hospitalization;
• Chronic use (>30 consecutive days) with an oral steroid at a dose equivalent to prednisolone ≥10 mg (eg, betamethasone ≥1.2 mg, dexamethasone ≥1.5 mg, hydrocortisone ≥40 mg) per day;
• Systolic BP > 180 or diastolic BP > 100 mmHg at randomization;
• Diagnosis of Type 1 diabetes mellitus, MODY (maturity onset diabetes of the Young) or diabetes mellitus secondary to diverse endocrinopathy, pancreatic resection, medication, pancreas neoplasia or chronic pancreatitis;
• History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time;
• History of any other malignancy within 5 years (with the exception of skin cancers successfully treated non-melanoma);
• Chronic cystitis and/or recurrent urinary tract infections (3 or more in the last year);
• Any condition that, in the opinion of the Investigator, may render the research participant unfit to complete the study, including, but not limited to, cardiovascular disease (KILLIP > 2, modified Forester > IIa,35 recurrent ventricular arrhythmias) or non cardiovascular (eg, active malignancy other than basal cell carcinoma, cirrhosis, chronic lung disease, severe autoimmune disease);
• Pregnancy or lactation;
• Active participation in another clinical trial
• Patients with septic shock or severe glycemic decompensation requiring the use of IV insulin at the time of randomization;
• TGP/ALT(Alanine Amino Transferase) >3x the upper limit of normality (ULN) or total bilirubin >2.5 x ULN;
• Estimated glomerular filtration rate (GFR) < 45 ml/min/1.73m² , calculated by MDRD, or kidney transplant;
• Known thrombophilias or thrombocytosis;
• Blood dyscrasias or any disorder that causes hemolysis, previously known;
• Hematological abnormality (Hb ≤ 11g/dL or > 17g/dL, leukocytes ≤ 4500/mm³ or >11000/mm³, platelet count <150,000/mm³ or > 450,000/mm³)