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.

Reduções dos níveis sangüíneos das frações lipídicas induzidas por sinvastatina e bezafibrato. Estudo multicêntrico Brasileiro / Atherorgenic Lipid Fraction Plasma Level Reductions Induced by Treatment with Simvastatin and Bezafibrate. Brazilian Multicenter Study

PURPOSE-To compare the effects of simvastatin and bezafibrate on the lipid profile to attain the objectives proposed by National Cholesterol Education Program (NCEP). METHODS--One hundred twenty six hypercholesterolemic patients (69 females and 57 men, 56.0 +/- 10.0 years old), after selection and placebo period (4 weeks) were maintained on lipid-lowering diet and were randomly assigned in a double-blind fashion to receive for 12 weeks, bezafibrate (B, 200mg t.i.d. - BG(n = 66)) or simvastatin (S, 10-40mg q.p.m. - SG(n = 60)). During the study, 28 patients (SG0) received S 10mg; in 14 patients (SG1) dosage was titrated to 20mg and in 18 cases (SG2) to 40mg. Clinical examination, lipid profile and safety determinations, and adverse effects were assessed in different periods of the study. RESULTS--Mean profile analysis showed different behaviour of BG, SG0, SG1 and SG2 through time for TC, TG, LDL-C and VLDL-C. Mean reductions of TC and LDL-C were more marked in SG (30.3 and 40.9) than in BG (18.8 and 24.8). BG showed greater increase of TG (33.7) and HDL-C (25.9) than did SG (16.3 and 7.7 respectively). Reduction greater than 30 (optimal responses) and between 20 and 29 (good responses) were more frequent in SG and LDL-C. BG showed greater frequency of good and optimal responses for TG reduction and HDL-C increase. NCEP goals were achieved in 75.4 of SG and 46.9 of BG (p = 0.001). No clinical or laboratorial adverse experiences were reported in any treatment groups. CONCLUSION--Simvastatin was more effective in the reduction of plasma levels of atherogenic lipid fractions (TC and LDL-C) and this treatment allowed earlier achievement of the goals proposed by NCEP in a greater number of patients

Objetivo - Comparar os efeitos da administração de sinvastatina e bezafibrato sobre o perfil lipídico sangüíneo para alcançar as proposições do Programa Nacional de Educação sobre Colesterol (NCEP) do Instituto Nacional de Saúde dos Estados Unidos. Métodos - Cento e vinte e seis hipercolesterolêmicos primários (69 mulheres e 57 homens, de 56,0±10,0 anos), após período de seleção e 4 semanas de placebo, foram alocados de modo cego e randomizado, para receber, durante 12 semanas, mantendo a orientação dietética, 200mg 3 vezes ao dia de bezafibrato (GB, n=66) e 10 a 40mg, à noite, de sinvastatina (GS, n=60). Em GS, durante o estudo, 28 pacientes foram mantidos com 10mg (GS0); em 14 (GS1), a dose foi aumentada para 20mg e em 18 (GS2) para 40mg Exames clínicos, determinações de variáveis do perfil lipídico sangüíneo, exames laboratoriais de controle e verificação de efeitos adversos foram realizados em diferentes períodos da investigação. Resultados - A análise do perfil de médias mostrou diferença de comportamento de GB, GS0, GS1 e GS2 ao longo do tempo para a colesterolemia total (CT), trigliceridemia (TG) e frações LDL-C e VLDL-C. Reduções médias de CT e LDL-C foram mais acentuadas em GS (30,3 e 40,9%) que em GB (18,8 e 24,8%). Em GB ocorreu maior redução de TG (33,7%) e aumento de HDLC (25,9%) que em GS (respectivamente 16,3 e 7,7%). Reduções superiores a 30% (resposta ótima) e entre 20-29% (resposta boa) foram mais freqüentes em GS para CT e LDL-C. GB teve maior freqüência de respostas boas e ótimas para a redução de TG e elevação de HDLC. Os objetivos do NCEP foram significantemente mais alcançados em GS (75,4%) do que em GB (46,9°/). Não ocorreram significativas reações adversas clínicas e/ou laboratoriais em GS e GB. Conclusão - A sinvastatina mostrou-se mais eficaz na redução dos níveis das frações aterogênicas (CT e LDL-C) e permitiu alcançar mais precocemente e em maior número de indivíduos os objetivos propostos pelo NCEP