2010, Number 3
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Cir Cir 2010; 78 (3)
Impacto del tratamiento con bezafibrato en pacientes con hiperfibrinogenemia e infarto agudo del miocardio con elevación del ST
Madrid-Miller A, Moreno-Ruiz LA, Borrayo-Sánchez G, Almeida-Gutiérrez E, Martínez-Gómez DF, Jáuregui-Aguilar R
Language: Spanish
References: 33
Page: 229-237
PDF size: 567.96 Kb.
ABSTRACT
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 STelevation 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 ± 12 .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 reductionwas associated with a lower incidence of major cardiovascular events.
REFERENCES
Olaiz G, Rojas R, Barquera S. Encuesta Nacional de Salud 2000. Tomo 2. La salud de los adultos. Cuernavaca, Morelos, México: Instituto Nacional de Salud Pública; 2003. pp. 18-21, 36-46.
Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases. I: General considerations, the epidemiologic transition, risk factors and impact of urbanization. Circulation 2001;104:2746- 2753.
Bodí V, Facila L, Sanchis J, Llácer A, Núñez J, Mainar L, et al. Pronóstico a corto plazo de los pacientes ingresados por probable síndrome coronario agudo sin elevación del segmento ST. Papel de los nuevos marcadores de daño miocárdico y de los reactantes de fase aguda. Rev Esp Cardiol 2002;55:823-830.
Mora S, Rifai N, Buring JE, Ridker PM. Additive value of immunoassay- measured fibrinogen and high-sensitivity C-reactive protein levels for predicting incident cardiovascular events. Circulation 2006;114:381-387.
Toss H, Lindahl B, Siegbahn A, Wallentin L. Prognostic influence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease (FRISC). Circulation 1997;96:4204-4210.
Gervois P, Vu-Dac N, Kleemann R, Kockx M, Dubois G, Laine B, et al. Negative regulation of human fibrinogen gene expression by peroxisome proliferator-activated receptor agonists via inhibition of CCAAT Box/enhancer-binding protein. J Biol Chem 2001;276:33471-33477.
Revert JM, Martínez-Lahuerta JJ, Ginés EA. Relación de la concentración plasmática de fibrinógeno con la edad, sexo y otros factores de riesgo cardiovascular. Semergen 2003;23:471-475.
Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors and long-term incidence of ischemic heart disease in the Northwick Park Heart Study. Lancet 1993;342:1076-1079.
Kannel WB, Wolf OA, Castelli WP, D’agostino RB. Fibrinogen and risk of cardiovascular disease. The Framingham Study. JAMA 1987;258:1183-1186.
Ernst E, Resch K. Fibrinogen as a cardiovascular risk factor: a metaanalysis and review of the literature. Ann Intern Med 1993;118:956- 963.
Ziakas A, Gavrilidis S, Giannoglou G, Souliou E, Gemitzis K, Kalampalika D, et al. In-hospital and long-term prognostic value of fibrinogen, CRP, and IL6 levels in patients with acute myocardial infarction treated with thrombolysis. Angiology 2006;57:283-293.
Marchioli R, Bomba E, Di Pasquale A, Geraci E, Giannuzzi P, Marfisi RM, et al. A nome dei Ricercatori GISSI-Prevenzione. La carta del rischio post-IMA: Risultati dei primi 18 mesi di follow-up del GISSI-Prevenzione. G Ital Cardiol 1998;28:416-433.
Borrayo SG, Almeida GE, Benítez PC, Madrid MA, Reyes HA, Velazco LG, et al. Estratificación temprana en pacientes con infarto agudo del miocardio con elevación del ST. Estudio ETIAM-ST. Primera fase. Rev Mex Cardiol 2007;18:17-23.
Borrayo SG, Contreras RA, Antezana CJ, Madrid MA, Reyes HA, Vélez TM, et al. Pronóstico de hiperfibrinogenemia en síndromes coronarios agudos. Rev Mex Cardiol 2004;15:151-194.
Gervois P, Kleemann R, Pilon A, Percevault F, Koenig W, Staels B, et al. Global suppression of IL6-induced acute phase response gene expression after chronic in vivo treatment with the peroxisome proliferator-activated receptor-α activator fenofibrate. J Biol Chem 2004;279:16154-16160.
Lindal B, Toss H, Siegbhan A, Venge P, Wallentin L. Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. N Engl J Med 2000;343:1139-1147.
Kockx M, Gervois PP, Poulain P, Derudas B, Peters JM, González FJ, et al. Fibrates suppress fibrinogen gene expression in rodents via activation of PPAR-alfa. Blood 1999;93:2991- 2998.
Staels B, Koenig W, Habib A, Merval R, Lebret M, Torra IP, et al. Activation of human aortic smooth muscle cells is inhibited by PPARalfa but not by PPAR-gamma activators. Nature 1998;393:790-793.
De Maat MP, Knipscheer HC, Kastelein JJP, Kluft C. Modulation of plasma fibrinogen levels by ciprofibrate and gemfibrozil in primary hyperlipidaemia. Thromb Haemost 1997;77:75-79.
Ericsson CG, Hamsten A, Nilsson J, Grip L, Svane B, Faire U. Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients. Lancet 1996;347:849-853.
Anon. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. Circulation 2000;102:21-27.
Behar S, for the BIP Study Group. Lowering fibrinogen levels: clinical update. Blood Coagul Fibrinolysis 1999;10:S41-S43.
Tenenbaum A, Motro M, Fisman EZ. Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. Cardiovasc Diabetol 2005;4:14.
Tatli E, Ozcelik F, Aktoz M. Plasma fibrinogen level may predict critical coronary artery stenosis in young adults with myocardial infarction. Cardiol J 2009;16:317-320.
Patterson CC, Smith AE, Yarnell JW, Rumley A, Ben-Shlomo Y, Lowe GD. The associations of interleukin-6 (IL6) and downstream inflammatory markers with risk of cardiovascular disease: The Caerphilly Study. Atherosclerosis (2009), doi:10.1016/j.atherosclerosis. 2009.09.030. [En prensa].
Goldenberg I, Benderly M, Goldbourt U; BIP Study Group. Secondary prevention with bezafibrate therapy for the treatment of dyslipidemia: an extended follow-up of the BIP trial. J Am Coll Cardiol 2008;51:459-465.
Madsen JK, Thomsen BL, Sorensen JN, Kjeldgaard KM, Kromann AB. Risk factors and prognosis after discharge for patients admitted because of suspected acute myocardial infarction with and without confirmed diagnosis. Am J Cardiol 1987;59:1064-1070.
Pierard LA, Dubois C, Smeets JP, Boland J, Carlier J, Kulbertus HE. Prognostic significance of angina pectoris before first acute myocardial infarction. Am J Cardiol 1988;61:984-998.
Anzai T, Yoshikawa T, Asakura Y, Abe S, Akaishi M, Mitamura H. Preinfarction angina as a major predictor of left ventricular function and long-term prognosis after a first Q wave myocardial infarction. J Am Coll Cardiol 1995;26:319-327.
Kloner RA, Muller J, Davis V. Effects of previous angina pectoris in patients with first acute myocardial infarction not receiving thrombolytics. MILIS Study Group. Multicenter Investigation of the Limitation of Infarct Size. Am J Cardiol 1995;75:615-616.
Bennermo M, Held C, Hamsten A, Strandberg LE, Ericsson CG, Hansson LO, et al. Prognostic value of plasma C-reactive protein and fibrinogen determinations in patients with acute myocardial infarction treated with thrombolysis. J Intern Med 2003;254:244-250.
Maresca G, Di Blasio A, Marchioli R, Di Minno G. Measuring plasma fibrinogen to predict stroke and myocardial infarction an update. Arterioscler Thromb Vasc Biol 1999;19:1368-1377.
Barbier O, Torra IP, Duguay Y, Blanquart C, Fruchart JC, Glineur C, et al. Pleiotropic actions of peroxisome proliferator-activated receptors in lipid metabolism and atherosclerosis. Arterioscler Thromb Vasc Biol 2002;22:717-726.