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Dapagliflozin Effects on Coronary Calcium and Epicardial Fat Assessed by Cardiotomography

H

Hilda Elizabeth Macías Cervantes

Status and phase

Completed
Phase 3

Conditions

Unstable Angina
Myocardial Infarction
Diabetes Mellitus, Type 2
Diabete Type 2

Treatments

Drug: Placebo
Drug: Dapagliflozin 10Mg Tab

Study type

Interventional

Funder types

Other

Identifiers

Details and patient eligibility

About

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

Full 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.

Enrollment

54 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Male and female patients over 18 years of age
  • Who meet the criteria of the fourth definition of infarction with and without ST segment elevation
  • Known with diabetes mellitus 2 or newly diagnosed diabetes according to ADA criteria

Exclusion criteria

  • Patients diagnosed with Type 1 Diabetes Mellitus
  • Patients on chronic replacement therapy for renal function using peritoneal dialysis or hemodialysis or with GFR less than 30 ml / min / 1.73m2
  • Patients who have recently undergone immunosuppressive therapy
  • Patients with a history of recurrent urinary tract infection
  • Patients known to be allergic to SGLT-2 inhibitors
  • Patients presenting as sudden aborted death.
  • Patients who after percutaneous coronary intervention require orotracheal intubation or present a state of shock

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

54 participants in 2 patient groups, including a placebo group

Dapagliflozin
Experimental group
Description:
Dapagliflozin 10 mg orally every 24 hours for 12 months
Treatment:
Drug: Dapagliflozin 10Mg Tab
Placebo
Placebo Comparator group
Description:
Placebo orally every 24 hours for 12 months
Treatment:
Drug: Placebo

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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