Effects of Simvastatin Versus Simvastatin Combined With Ezetimibe on Blood Coagulation in Patients With Acute Coronary Events: Relationship With Cholesterol-Lowering and Anti-Inflammatory Properties

Clinical status will be evaluated during hospitalization, and then on the out-patient basis. All cardiovascular events (fatal or nonfatal myocardial infarction, unstable angina, sudden cardiac death, all-cause death, stroke, TIA) will be recorded and the patients who underwent acute PCI will have a follow-up coronary angiography performed according to current recommendations. However, the clinical analysis is not a major gaol of this study.

The investigators plan to evaluate following parameters:

• Whole blood morphology, creatinine, glucose, sodium, potassium, urea, lipid profile, CK, AST, fibrinogen, using standard methods in hospital laboratory.
• Inflammation markers - fibrinogen (nephelometry, Dade Behring) high-sensitivity C-reactive protein (nephelometry, Dade Behring); interleukin 6 (ELISA, R&D Systems).
• Thrombin generation markers in peripheral blood - thrombin-antithrombin complexes [TAT] (ELISA, Dade Behring); prothrombin fragments 1+2 [F1+2] (ELISA, Dade Behring).
• Fibrin clot permeation and susceptibility to lysis - measurement of Darcy's constant (dimensions of pores in the structure of the clot) by measurement of volume of buffer (0,05 mol/l Tris HCl with 0,15 mol/l NaCl) penetrating through the fibrin gel made in polystyrene pipes, 1.3 mm in diameter, with 100 ul of citrate plasma and after addition of 1U/ml human thrombin and 20 mmol/l calcium chloride in room temperature within 120 minutes according to methodology described by Mills and al.
• Fibrin gel turbidimetry - plasma mixed with Tris buffer prepared as mentioned above in 2:3 ratio, after addition 1 U/ml thrombin and 16 mmol/l calcium chloride will be analyzed in the UV spectrometer (wave length 405 nm). Following variables will be measured: initiation time, absorption increasing time and absorption value in plateau, approximately 10 minutes after addition of thrombin to the mixture. After 2 hours, spectrophotometry assessment of the clot will be performed (400 to 800 nm) to measure the pore size and thickness of fibrin fibers using the Carr equation modified by Wolberg. Then fibrinolysis of fibrin gel will be measured by means of turbidimetry. Another lysis assay based on the measurement of D-dimer levels in the effluent flowing through fibrin gels will be performed according to the method of Collet et al.
• Activation of the coagulation system in a "minimally modified blood" model according to Rand et al. Non-anticoagulated blood will be divided into 10 1-ml samples added to the tubes with TF and phospholipids, and then clotting will be stopped by an anticoagulant cocktail. In the supernatant samples, Western blotting and HPLC analysis of fibrinopeptides will be performed as described previously.

In 40 patients allocated at a random we will assess activation of coagulation system using the vascular injury model according to a procedure developed by us.

We will measure: