Early Effect Of Bezafibrate On Fibrinogen Levels, Inflammatory Response And Clinical Impact, In Patients With ST Elevation Acute Myocardial Infarction

Patients >18 years of age who were admitted to the Cardiovascular Intensive Care Unit of the Cardiology Hospital, National Medical Center, Century XXI (Mexico City) and diagnosed with ST segment elevation Acute Coronary Syndrome (ACS) and hyperfibrinogenemia within 72 h of symptom onset were included. Acute myocardial infarction (AMI) was diagnosed when high myocardial necrosis markers were found such as CPK total >150% basal value or troponin I ≥1 ng/ml plus one of the following: ischemic precordial pain >30 min with/without dyspnea, diaphoresis, nausea, vomiting, or ST segment elevation >1 mm in two or more contiguous leads or left bundle branch block, new or presumed new. Hyperfibrinogenemia was diagnosed after fibrinogen concentrations reached >500 mg/dl at 72 h of evolution. All patients signed an informed consent form to participate in the study.

Patients with known bezafibrate allergy, previous fibrate treatments, patients with cardiogenic shock, hepatic failure, renal failure, history of neoplastic disease, chronic inflammatory disease or active infectious process, anti-inflammatory or immunosuppressive therapies, fibrinolysis with streptokinase and patients with triglyceride concentrations >150 mg/dl were excluded.

Patients were classified into two groups: group I, patients who received a 400-mg bezafibrate dose every 24 h plus conventional anti-ischemic therapy; and group II, patients who only received conventional anti-ischemic therapy. Patients were assigned to each group using random numbers tables. Conventional adjunctive anti-ischemic therapy included dual antiplatelet therapy, antithrombotic, beta blockers, statins, angiotensin converting enzyme inhibitors, and others according to each case. Twelve-lead ECG was carried out daily and under recurrent ischemic event. Laboratory tests were also carried out including cardiac enzymes, lipid profile and CRP.

Our goal was to determine if bezafibrate therapy combined with conventional anti-ischemic therapy reduces fibrinogen levels. Primary endpoints were recurrent ischemic event such as reinfarction or post-infarction angina and left ventricular failure. Secondary endpoints were death, need for revascularization and combined clinical endpoints that will be presented after randomization and before patient discharge.

Blood samples were taken in all patients by venipuncture in an upper extremity (Vena basilica, cephalic or any tax): 4.5 ml of blood, collected into a 0.5 ml tube vacutainer with sodium citrate buffer (9: 1) 0129 M 3.8% (blue top), which is used to determine the coagulation time and fibrinogen; and another 7 ml, which will be collected in vacutainer tubes dry (red cap). The samples will be centrifuged at 2000 rpm for 10 min and the serum obtained will be divided into aliquots of 200 ul to keep at -70 ° C for subsequent biochemical determinations. This procedure will be performed on admission to the Cardiovascular Intensive Care Unit and on days 5, 7 and 30 of its randomizationAll patients after hospital discharge, will be cited by telephone at 30 days after randomization, for taking blood samples, as well as for clinical evaluation.Fibrinogen Determination All venous blood samples (4.5 ml) will be taken from an upper limb (basilic vein, cephalic vein or any of their tributaries) and collected in a Vacutainer (Becton Dickinson, Franklin Lakes, NJ) tube with 0.5 ml sodium nitrate buffer (9:1) 0.129 M 3.8% (blue top). This procedure was repeated at discharge or after 7 days when the patient was subjected to a long hospital stay. PT-Fibrinogen HS Plus kit (Beckman Coulter, Brea, CA) was used. This contains high-sensitivity calcium thromboplastin to determine prothrombin time and fibrinogen and to evaluate extrinsic pathway of coagulation in citrated human plasma using an auto-analyzer ACL-800 (Cobas, Roche Diagnostics, Indianapolis, IN) where fibrinogen levels are determined through turbidimetry. Test measure correlation was r = 0.95. Units reported for fibrinogen are mg/dl and the standard control is 273 mg/dl with a linearity of 700 mg/dl.