Role of dapagliflozin in ischemic preconditioning in patients with symptomatic coronary artery disease
Patients with documented multivessel coronary artery disease, documented ischemia by stress testing and preserved left ventricular ejection fraction (LVEF)
Ischemic preconditioning (IP) is a powerful cellular protection mechanism. The cellular pathways underlying IP are extremely complex and involve the participation of cell triggers, intracellular signaling pathways, and end-effectors. Experimental studies have shown that sodium-glucose transport protein 2 (SGLT2) inhibitors promote activation of 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK), the main regulator of adenosine 5′-triphosphate homeostasis and energy metabolism in the body. Despite its cardioprotective profile demonstrated by numerous clinical trials, the results of studies on the action of SGLT2 inhibitors in IP are scarce. This study investigates the effects of dapagliflozin on IP in patients with coronary artery disease (CAD). Briefly, patients will undergo 4 exercise tests, the first two, with a time interval of 30 minutes between them, after the washout period of cardiovascular or hypoglycemic medications and, the last two, after 7 days of dapagliflozin 10 mg once a day, also with a time interval of 30 minutes between them. Patient preparation After clinical and cardiological evaluation, patients will be instructed to stop medications with cardiovascular effects before sequential exercise tests, depending on the half-life of the drug. Diabetic patients will be instructed to suspend medications with cardiovascular effects and oral hypoglycemic agents for a similar period before the tests. Only nitrates will be maintained, when necessary, up to 24 hours before testing. Patients will be instructed not to perform physical activities during the test period, to control their salt intake and patients with diabetes will be advised to strictly control their carbohydrate intake. They will also be instructed to contact the study team by telephone, who will be available 24 hours a day, in case of questions or worsening of symptoms. On the day of the exams, the symptoms will be reassessed by the medical team before carrying out the sequential
1. Stable multivessel coronary artery disease (obstruction greater than 70% in at least 2 main coronary branches). 2. LVEF ≥0.50, confirmed by transthoracic Doppler echocardiography. 3. Documentation of stress-induced myocardial ischemia (horizontal or descending ST segment depression ≥ 1.0 mm)
1. Kidney failure (creatinine clearance < 60 ml/min) 2. Severe liver failure 3. Single-vessel coronary artery disease 4. Myocardial infarction in the last 3 months 5. LVEF < 50% 6. Presence of any non-ischemic cardiomyopathy 7. Moderate or severe valve disease 8. Morphological changes in the qrs of the ecg and conduction defects that may interfere with the interpretation of changes in the st segment 9. Recent and negative exercise test for myocardial ischemia 10. Positive exercise test for myocardial ischemia, with signs of high risk 11. Limiting anginal symptoms or recent worsening 12. Arrhythmias that make it difficult to characterize myocardial ischemia during exercise stress (atrial fibrillation or flutter) 13. Patient refusal to participate in the study