Dapagliflozin Effects on Coronary Calcium and Epicardial Fat Assessed by Cardiotomography
Condition: Diabete Type 2; Unstable Angina; Myocardial Infarction; Diabetes Mellitus, Type 2
MeSH terms: Myocardial Infarction; Angina, Unstable; Diabetes Mellitus, Type 2; Infarction
Study type: Interventional
Phase: Phase 3

Summary: 
      Calcification of the coronary arteries is a direct sign of atherosclerotic disease of the
      coronary arteries and has been shown to be a strong predictor of the risk of cardiovascular
      diseases, including myocardial infarction and/or cardiac death, especially in patients with
      Diabetes Mellitus type 2. Therefore, there is great interest in pharmacotherapies that
      improve the rates of cardiovascular complications, and modify the outcomes of this group of
      patients.

      Large randomized controlled trials with SGLT2 inhibitors in patients with DM2 have shown a
      clear reduction in cardiovascular events among individuals with atherosclerotic disease.
      Atherosclerosis imaging allows measurable assessments of disease progression and activity,
      revealing early signs of potential drug effects. Noninvasive methods are preferred for serial
      imaging in drug trials due to the potential risks associated with invasive procedures. The
      coronary artery calcium quantification using the Agatston score is the most widely used
      method
    

Detailed description: 
      It is now well recognized that Coronary Artery Disease (CAD) is part of the spectrum of
      cardiovascular diseases (CVDs) that have common underlying risk factors and may manifest as
      myocardial infarction, stroke or death.

      CAD is a pathological process characterized by the accumulation of atherosclerotic plaque in
      the epicardial arteries, whether obstructive or non-obstructive; it can have long and stable
      periods, but it can also become unstable at any time.

      It is unknown whether the high risk provided by the presence of obstructive coronary artery
      atherosclerotic disease is due to stenosis per se, or due to its correlation with the total
      burden of atherosclerotic plaque. Studies suggest that calcified atherosclerotic burden, not
      stenosis, is the main predictor of future events of cardiovascular disease (myocardial
      infarction and cerebrovascular disease) and death in patients with coronary artery disease.

      Atherosclerosis imaging allows measurable assessments of disease progression and activity,
      revealing early signs of potential drug effects. Non-invasive methods are preferable for
      serial imaging in drug trials because of the potential risks associated with invasive
      procedures. High participant dropout rates are also observed when invasive methods are used.

      Therefore, coronary artery calcium scanning offers a simple, non-invasive, rapid, and
      reliable method to quantify coronary calcium, which is pathognomonic for established
      atherosclerosis. It is a powerful screening tool for asymptomatic patients at low or
      intermediate risk of CVD, including those with diabetes mellitus, and can potentially improve
      adherence to lifestyle advice and medication.

      Coronary artery calcium can be quantified by non-contrast-enhanced CT using the Agatston
      score, which is currently the most widely used method. Conceptually, the Agatston score is
      the sum of the scores for all calcified coronary lesions, representing both the total area
      and the maximum density of coronary calcification. The area of the lesion is multiplied by
      the density factor that is determined by pre-defined cut points. The density factor is used
      so that the regions with higher attenuation contribute more strongly to the final calcium
      score. A CT attenuation threshold of 130 Hounsfield units (HU) is used for calcium detection,
      and only contiguous voxels totaling an area greater than 1 mm2 are counted as "lesions" to
      reduce the influence of image noise. Standardized categories have been developed for the
      calcium score with scores of 0 indicating the absence of calcified plaque, 1 to 10 minimal
      plaque, 11 to 100 mild plaque, 101 to 400 moderate plaque, and > 400 severe plaque.

      In 2017, the Society of Cardiovascular Computed Tomography (SCCT) and the Society of Thoracic
      Radiology (STR) proposed the CAC-DRS as a way to standardize communication regarding CAC
      findings on non-contrast-enhanced CT scans. CAC-DRS categories are defined as Ax/Ny, where A
      represents the Agatston score group (where A0, A1, A2, and A3 represent CAC of 0, CAC of
      1-99, CAC of 100-299, and CAC ≥ 300, respectively), and N represents the number of vessels
      affected by CAC, ranging from 0 to 4 for the major epicardial coronary arteries.,
      respectively), and N represents the number of vessels affected by CAC, which varies from 0 to
      4 for the main epicardial coronary arteries.
    

Intervention name(s): Dapagliflozin 10Mg Tab; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): patients who meet the inclusion criteria and after catheterization will be randomized to receive Dapagliflozin 10 mg every 24 hours and upon dischargetreatment will continue for 12 months; patients who meet the inclusion criteria and after catheterization will be randomized to receive a placebo pill 24 hours and upon discharge treatment will continue for 12 months
Other intervention name(s): Forxiga; Placebo pill
Intervention MeSH terms: Dapagliflozin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Any patient presenting with a diagnosis of acute myocardial infarction with and without ST segment elevation will be explained the objective of the study and after performing percutaneous coronary intervention they will be randomized using an excel sheet to one of two groups, the intervention group will receive Dapagliflozin 10 mg every 24 hours and the control group will receive placebo. In both groups, a simple cardiotomography was performed to evaluate the calcium score and epicardial fat at baseline and after 12 months of intervention.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Dapagliflozin; coronary calcium; Atherosclerosis; Myocardial Infarction; Agatston score