Impacto del tratamiento con bezafibrato en pacientes con hiperfibrinogenemia e infarto agudo del miocardio con elevación del ST / Impact of bezafibrate treatment in patients with hyperfibrinogenemia and ST-elevation acute myocardial infarction: a randomized clinical trial

Introducción: La hiperfibrinogenemia se considera predictora de eventos cardiovasculares en sujetos sanos y pacientes con cardiopatía isquémica. Como medida de prevención primaria, el bezafibrato disminuye el fibrinógeno sanguíneo y los eventos cardiovasculares, pero su efecto en el síndrome coronario agudo aún no se conoce. Material y métodos: Ensayo clínico, aleatorizado, controlado con tratamiento convencional. Se incluyeron pacientes con infarto agudo del miocardio con elevación del segmento ST y concentraciones de fibrinógeno > 500 mg/dl a las 72 horas de evolución. Se asignaron a recibir 400 mg de bezafibrato (grupo I) o tratamiento convencional (grupo II). Punto primario de evaluación: concentraciones de fibrinógeno; puntos secundarios: recurrencia de angina o infarto, falla ventricular izquierda y puntos finales combinados durante la estancia hospitalaria. Resultados: Se incluyeron 25 pacientes por grupo. Las concentraciones de fibrinógeno al egreso hospitalario fueron significativamente menores en el grupo I (532.42 ± 129.6 versus 889 ± 127.32 mg/dl del grupo II, p < 0.0001). Los puntos secundarios se presentaron con mayor frecuencia en el grupo II que en el grupo I: angina (56 versus 4%, riesgo relativo 0.071 [0.010-0.503], p < 0.0001), falla ventricular (24 versus 4%, riesgo relativo 0.167 [0.022-1.286], p = 0.049) y puntos finales combinados (76 versus 8%, riesgo relativo 0.105 [0.027- 0.405], p < 0.001). Conclusiones: El tratamiento con bezafibrato fue seguro y logró reducir el fibrinógeno en pacientes con infarto agudo. Esta reducción se asoció con menor frecuencia de eventos cardiovasculares a corto plazo.

BACKGROUND: Hyperfibrinogenemia is a predictor of cardiovascular events in healthy subjects and in patients with chronic ischemic heart disease. Bezafibrate decreases fibrinogen levels and also the incidence of major cardiovascular events in primary prevention, but its effects in acute coronary syndrome are unknown. METHODS: This is a randomized, controlled clinical trial with conventional therapy. We included patients with Acute ST Elevation Myocardial Infarction (STEAMI) and fibrinogen concentration >500 mg/dl at 72 h of evolution. We randomized subjects into two groups: bezafibrate 400 mg (group I) and conventional therapy (group II). Primary end point was decrease of fibrinogen concentrations. Secondary end points were recurrence of angina or infarction, left ventricular failure and combined end points during hospitalization. RESULTS: We included 25 patients in each group. Fibrinogen concentrations were lower at hospital discharge in Group I than in Group II (532.42 +/- 129.6 vs. 889 +/- 127.32 mg/dl in group II, p <0.0001). Secondary end points were more frequent in Group II than in Group I: angina (56% vs. 4%, RR 0.071 [0.010-0.503], p <0.0001), left ventricular failure (24% vs. 4%, RR 0.167 [0.022-1.286], p = 0.049) and combined end points (76% vs. 8%, RR 0.105 [0.027-0.405], p <0.001). CONCLUSIONS: Bezafibrate treatment was a safe treatment and reduced fibrinogen levels in patients with STEAMI and hyperfibrinogenemia. In the short term, this reduction was associated with a lower incidence of major cardiovascular events.

role of bezafibrate in lowering risk factors for cardiovascular disease in diabetic patients

A number of hypolipidaemic drugs have been shown to lower the raised plasma fibrinogen concentrations indicating that lipid and haemostatic system may act synergistically in pathogenesis of cardiovascular diseases. The current study examines the possible role of lipid lowering drug bezafibrate to induce change in blood coagulation system and the architecture of fibrin network in addition to its known effects on lipid profile in diabetic patients. Methods based on turbidity for measurement of mass length ratio of fibrin fibers, permeability of the networks and their tensile strength have been used to assess the alterations induced by lipid lowering agent. The study group consisted of 38 patients [18 male and 20 female; age 40 - 65 years]. The patients were categorized into two groups. Group one included 20 diabetic patients, selected from Liaquat National Hospital, Karachi, with normal lipid profile as control [9 male, age 51.88 +/- 1.93 years; 11 female, age 48.36 +/- 2.44 years]. Second group included 18 diabetic patients, selected from National Institute of Cardiovascular Disease, Karachi, with altered lipid profile i.e. hypertriglyceridaemia and/or hypercholesterolemia [9 male, age 47.33 + 3.08 years; 9 female, age 48.66 +/- 3.99 years]. Blood samples were collected after 12-14 hours fasting at the start of the study and after administration of Bezafibrate [200 mg TDS] for 4 weeks. The samples were analyzed for blood parameters like cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], triacylglycerol [TG],-and fibrin network characteristics. In addition to the changes in lipid profile, significant alterations were observed in the characteristics of fibrin networks by the drug. Amongst the changes induced are the properties of networks that make the networks more lysable by fibrinolytic agents. Clinical and pharmacological implications of these findings need further investigations

Flowcytometric evidence of platelet activation in patients on aspirin following myocardial infarction.

BACKGROUND: Following a myocardial infarction, patients are usually started on long term antiplatelet therapy with aspirin in a dose of 80-150 mg/day. However, there are no quick and easy methods to assess the efficacy of the antiplatelet activity of aspirin. METHODS: We studied 60 consecutive patients (men, < 40 years of age) 8-10 weeks after they had had acute myocardial infarction. These patients were receiving 100 mg aspirin daily orally with or without b-blockers. We measured P-selectin expression and fibrinogen binding by flowcytometry at least 3 times over a period of 2 years in all the patients. We also studied 100 age- and sex-matched controls. RESULTS: Of the 60 patients, 30 (50%) showed both increased P-selectin and fibrinogen binding by platelets, suggesting platelet activation. Fourteen other patients had increased fibrinogen binding but normal P-selectin expression. Sixteen patients and all the controls had normal results of both tests. CONCLUSION: Our data show evidence of platelet activation in at least 50% of patients receiving 100 mg of aspirin daily. Flowcytometry for P-selectin expression and fibrinogen binding to platelets can be used to monitor antiplatelet therapy with aspirin following acute myocardial infarction.

Comparing the effect of two different hormonal therapy regimens on the activity coagulation factors VII, VIII, IX and serum lipids in menopausal women

During extrinsic coagulation pathway, a complex is developed between factor VII, calcium and tissue factor [a cell membrane lipoprotein that is exposed after cell injury]. Factor VII needs calcium and vitamin K for its biologic activation. Coronary artery disease [CAD] can be induced by increased level and activity of the coagulation factors VII, VIII and IX. In postmenopausal women, estrogen decreases blood lipids and thereby decreases risk of CAD. However, the exact effects of the estrogen on the other predisposing factors of CAD are unknown. This study was conducted to evaluate the effects of oral hormone therapy regimen on fibrinogen and other coagulation factors. Sixty menopausal women with history of hysterectomy were randomly allocated in 2 groups. One group was treated with conjugated estrogen 0.625 mg/day and the other group was treated with conjugated estrogen 0.625 mg/day and medroxyprogesterone 2.5 mg/day. Serum fibrinogen level and activity of coagulation factors VII, VIII and IX and blood lipids level were checked before and 3 months after treatment. In the group treated with estrogen alone, mean factor VII activity showed significant increase 3 months after treatment as compared to before hormone therapy [P<0.05]. There were no significant changes in mean activities of coagulation factors VIII, IX and serum fibrinogen level in patients treated with estrogen or estrogen/medroxyprogesterone after treatment [P>0.05]. In both groups, hormone therapy significantly decreased serum cholesterol level and LDL-C and increased HDL-C [P>0.00], but serum triglyceride level increased in the group only treated with estrogen. Significant increase of coagulation factor VII and serum triglyceride in estrogen-treated patients is logical. This study confirms that hormone therapy with this protocol does not change mean serum fibrinogen levels and activity of coagulation factor VIII and IX. This may be a genuine finding or may be due to inadequacy of samples, given the wide normal range of coagulation factors and serum fibrinogen. Studies with more prolonged follow-up or more samples are warranted

Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B

Activation of hepatic stellate cells is the earliest step in fibrogeneesis. Alpha-smooth muscle acting [alpha-SMA], expressed by activated hepatic sallate cells, and C-terminal procollagen alpha [III] propeptide [PIIICP] are early markers of fibrogenesis and should precede fibrosis. ASD: Determine if suppression of hepatitis B virus replication with lamivudine would decrease fibrogenesis as measured by immunohistochemical markers. Paried liver biopsies from patients with hepatitis B before and after therapy with lamivudine [n=47] or placebo [n=33] were studied. Alpha-SMA and PIIICP were detected in paraffin-embedded tissue by immunohistochemistry and quantified in a blinded manner by video imaging analysis. Liver biopsies from patients treated with lamivudine showed a significant decrease in alpha-SMA expression [1.06 +/- 0.23 vs. 0.58 +/- 0.11, pre vs. post, P< 0.05]. Placebo recipients had increased levels of alpha -SMA 0.82 +/- 0.14 vs. 1.32 +/- 0.21, P< 0.05]. PIICP was similarly decreased after lamivudine. Among subjects whose Histological Activity Index fibrosis score was unchanged or worsened, the mean changes in alpha-SMA expression was significantly decreased in the lamivudine group compared with placebo. Lamivudine decreased markers of hepatic satellite cell activation and collagen synthesis. Immunohistochemical techniques are sensitive for assessing fibro-genesis and will be useful in trials of antiviral and antifibrotic agents

Effect of various antihypertensive drugs on plasma fibrinogen levels in patients with essential hypertension.

In recent years, substantial evidence has accumulated to unambiguously implicate high plasma fibrinogen levels as a major cardiovascular risk factor. An open prospective and randomised pilot study was therefore undertaken in mild to moderate hypertensives to evaluate the effect of various antihypertensive drugs viz enalapril, felodipine and prazosin on the blood pressure and plasma fibrinogen levels. The systolic and diastolic blood pressures were determined at 0, 4 and 8 weeks whereas plasma fibrinogen assays were done at baseline and at the end of the 8th week of treatment in all the drug-treated groups. It was observed that although all the three drugs effectively controlled blood pressure, only enalapril significantly reduced plasma fibrinogen levels. Due to this additional effect, enalapril has potential to control two major cardiovascular risk factors--hypertension and high plasma fibrinogen levels--simultaneously.