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Effects of low-molecular-weight heparin (Enoxaparin) versus a direct thrombin inhibitor (Dabigatran) on platelet aggregation in patients with Stable Coronary Artery Disease

Grant number: 12/11750-8
Support type:Regular Research Grants
Duration: May 01, 2013 - October 31, 2015
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:José Carlos Nicolau
Grantee:José Carlos Nicolau
Home Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers: Flávia Bittar Britto Arantes ; Karin Deguirmendjian Rosa Campos

Abstract

Anticoagulation with heparin is indicated in several situations, such as acute coronary disease (in combination with antiplatelet therapy) for the prevention and treatment of venous thromboembolism and situations with high risk of thromboembolism, such as atrial fibrillation, hemodialysis and invasive procedures such as radiofrequency ablation, among others. However some studies about interaction between heparin and platelet aggregation have shown conflicting results: while some suggest an inhibitory effect of heparin on platelet function, others suggest that heparin could promote an increase in platelet activation.More recently, new antithrombotic strategies include anti-Xa and competitive inhibitor of thrombin like Dabigatran. This was tested in two large phase III studies: the RE-MODEL study demonstrated efficacy and safety similar to Enoxaparin on preventing venous thrombosis in patients undergoing prosthetic knee surgery; in the RE-LY, Connoll SJ et al compared Dabigatran using doses of 110 and 150 mg twice a day with Warfarin, targeting the prevention of thromboembolic events in patients with chronic atrial fibrillation. In this study, 150 mg of Dabigatran twice a day was associated with lower incidence of thromboembolic and hemorrhagic stroke, with incidence of major bleeding similar to that of Warfarin, by contrast, Dabigatran on a dose of 110 mg twice a day was as effective as Warfarin, with a significant reduction on the incidence of bleeding events.The present study aims to assess the effects of the LMWH Enoxaparin and direct thrombin inhibitor, Dabigatran, on platelet aggregation, studied and compared by different methods in patients with chronic coronary artery disease (CAD). This is a randomized, prospective and open study, with laboratory tests performed in a blinded fashion. This will include 30 patients with chronic CAD, stable, using ASA.All patients will receive the same medications in effective doses recommended at each stage of the study, so that every individual is his self-control, the Enoxaparin will be administrated at a dose of 1mg/kg twice a day and Dabigatran at a dose of 150mg twice a day. Laboratory tests: Flow cytometry, whole blood aggregometry, PFA (platelet function analyzer) -100 ®, Verify Now Aspirin ®, Thromboelastography, Impact-R, thromboxane B2 serum and IL-6, CBC with platelet count, coagulation tests, levels of ALT, AST, creatinine, urea, glucose, glycated hemoglobin and lipid profile. Study Design: Phase 1 : There will be a first collection of blood samples from all patients at baseline for laboratory tests, then the patient will be randomized to initial use of Enoxaparin or Dabigatran.Phase 2: Dabigatran will be administrated for 5 days and laboratory tests including platelet aggregation will be made, or Enoxaparin will be administrated for 5 days and the same tests will be performed.Phase 3: After 30 days Enoxaparin will be administrated for 5 days in individuals who received Dabigatran at Phase 2, and Dabigatran will be administrated for 5 days in individuals who received Enoxaparin in Phase 2. The same laboratory tests including platelet aggregation will be performed. (AU)