Estatinas en la insuficiencia cardiaca
DOI:
https://doi.org/10.51481/amc.v51i2.225Palabras clave:
insuficiencia cardiaca, estatinasResumen
Desde su descubrimiento hace cerca de 30 años, las estatinas han desempeñado un papel importante en el tratamiento y prevención de las enfermedades cardiovasculares, con base, inicialmente, en las propiedades hipolipemiantes de esta clase de fármacos. Con el advenimiento de nuevos conocimientos sobre su mecanismo de acción y de sus propiedades pleiotrópicas, se ha planteado la utilidad clínica de las estatinas en diversas enfermedades. Ha surgido evidencia sugestiva de la eficacia de estos fármacos en la insuficiencia cardiaca a partir de múltiples teorías. A continuación se revisan el fundamento fisiopatológico que sustenta su utilización en este síndrome y la actual evidencia clínica en favor o en contra de tal uso.
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Plehn J, Davis B, Sacks F, Rouleau J, Pfeffer M, Bernstein V. Reduction of stroke incidence after myocardial infartion with pravastatin: The cholesterol and recurrent events (CARE) study. Circulation. 1999; 99: 216-223.
Heart Protection Study Collaborative Group. MRC / BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high – risk individuals: a randomized placebo – controlled trial. Lancet. 2002; 360: 7-22.
Raina A, Pickerin T, Shimbo D. Statin use in heart failure: A cause of concern? Am Heart J. 2006; 152:39-49.
Aronow W. Epidemiology, Pathophysiology Prognosis and Treatment of Systolic and Diastolic Heart Failure. Cardiol Rev. 2006; 14:108124.
Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006; 355:251-259
Ulate-Montero G, Ulate-Campos A. Actualización en los mecanismos fisiopatológicos de la insuficiencia cardiaca. Act Med Costarric. 2008; 50: 5-12.
Hoshijima M, Sah V, Wang Y, Chien K, Heller J. The low molecular weight GTPase rho regulates myofibril formation and organization in neonatal rat ventricular myocites. Biol Chem. 1998; 273:7725-7730.
Wettschureck N, Offermanns S. Mammalian G proteins and their cell type specific functions. Physiol Rev. 2005; 85:1159-1204.
Satoh M, Ogita H, Takeshita K, et al. Requirement of Rac1 in the development of cardiac hypertrophy. PNAS. 2006; 103:7432-7437.
Auki H, Izumo S, Sadoshima J. Angiotensin II activates RhoA in cardiac myocites. Circ Res. 1998; 82:666-676.
Satoh S, Ueda Y, Koyanagui M, Kadokami T, Sugano M, Yoshikawa Y, Makino N. Chronic inhibition of Rho Kinase blunts the process of left ventricular hypertrophy leading to cardiac conctractile dysfunction in hypertensive – induced heart failure. J Mol Cell Cardiol. 2003; 35:59-70.
Frey N, Katus H, Olson E, et al. Hypertrophy of the heart. Circulation 2004; 109:1580-1589.
Pimentel D, Amin J, Xiao L, Miller T, Viereck J, Olivier-Krasinski J, et al. Reactive Oxygen Species mediate amplitud-dependant hypertrophic and apoptotic responses to mechanical stretch in cardiac myocites. Circ Res. 2001; 89:453-460.
Nojiri H, Shimizu T, Funakoshi M, Yamaguchi O, Zhou H, Kawakami S. Oxidative Stress causes heart failure with impaired mithocondrial respiration. J Biol Chem. 2006; 281:33789-33801.
Liu H, Colavitti R, Rovira I, Finkel T. Redox-Dependant transcriptional regulation. Circ Res. 2005; 97:967-974.
Giordano F. Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest. 2005; 115:500-508.
Cheng TH, Cheng PY, Shih NL, Chen IB, Ling D, Chen JJ. Involvement of reactive oxygen species in angiotensin II – induced endothelin – 1 gene expression in rat cardiac fibroblasts. J Am Coll Cardiol. 2003; 42:1845-1854.
Takimoto E, Kass D. Role of oxidative stress in cardiac hypertrophy and remodeling Hypertension. 2007; 49:241-248.
Endemann D, Schiffrin E. Endothelial dysfunction. J Am Soc Nephrol. 2004; 15:1983-1992.
Taniyama Y, Griendling K. Reactive Oxygen Species in the Vasculature. Hypertension. 2003; 42:1075-1081.
López A, Casado S. Heart Failure, redox alterations, and endothelial dysfunction. Hypertension. 2001; 38:1400-1405.
Ramos-Esquivel A, León-Céspedes C. Efectos no hipolipemiantes de las estatinas. Act Med Costarric. 2007; 49: 182-189.
Liao JK. Isoprenoids as mediators of the biological effects of statins. J Clin Invest. 2002; 110:285-288.
Takemoto M, Node K, Nakagami H, Liao Y, Grimm M, Takemoto Y, et al. Statins as antioxidant therapy for preventing cardiac myocite hypertrophy. J Clin Invest. 2001; 108:1429-1437.
Haendeler J, Hoffman J, Zeiher A, Dimmeler S. Antioxidant effect of statins via S-nitrosylation and activation of thioredoxin in endothelial cells. Circulation. 2004; 110:856-861.
Zhang H, Schmeiber A, Garlichs C, Plötze K, Damme U, Mügge A, et al. Angiotensin II-induced superoxide anion generation in human vascular endothelial cells: Role of membrane-bound NADH-/ NADPH-oxidases. Cardiovasc Res. 1999; 44: 215-222.
Wassmann S, Laufs U, Bäumer A, Müller K, Konkol C, Sauer H et al. Inhibition of geranylgeranylation reduces angiotensin II-mediated free radical production in vascular smooth muscle cells: involvement of angiotensin AT1 receptor expression and Rac1 GTPase. Mol Pharmacol. 2001; 59:646-654.
Dechend R, Fiebeler A, Park JK, Müller D, Theur J, Mervaala E, et al. Amelioration of angiotensin II – induced cardiac injury by a 3hydroxy-3-methyglutaryl coenzyme A reductase inhibitor. Circulation. 2001; 104:576-581.
Pliquett R, Cornish K, Zucker I. Statin therapy restores sympathicovagal balance in experimental heart failure. J Appl Physiol. 2003; 95:700704.
Pliquett R, Cornish K, Peuler JD. Simvastatin normalizes autonomic neural control in experimental heart failure. Circulation. 2003; 107:2493-2498.
Gao L, Wang W, Li YL, Shultz HD, Liu D, Cornish KG, et al. Simvastatin therapy normalizes sympathetic neural control in experimental heart failure. Circulation. 2005; 112:1763-1770.
Tousoulis D, Antoniades C, Bosinakou E, Kotsopoulou M, Pitsavos C, Vlachopoulos C, et al. Effects of atorvastatin on reactive hyperemia and inflammatory process in patients with congestive heart failure. Atherosclerosis. 2005; 178:359 - 63.
Sola S, Mir M, Lerakis S, Tandon N, Khan B. Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. J Am Coll Cardiol. 2006; 47:332-337.
May H, Muhlestein J, Carlquist J, Horne B, Campbell, Kfoury A, et al. Relation of serum total cholesterol, c-reactive protein leveles and statin therapy to survival in heart failure. Am J Cardiol. 2006; 98:653658.
Node K, Fujita M, Kitakaze M, Hori M, Liao J. Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation. 2003;108:839-843.
Strey CH, Young JM, Lainchbury JH, Frampton C, Nicholls M, Richards A, et al. Short term statin treatment improves endothelial function and neurohormonal imbalance in normocholesterolaemic patients with non – ischemic heart failure. Heart. 2006; 92:16031609.
Schäfer A, Fraccarollo D, Eigenthaler M, Tas P, Firnschild A, Frantz A, et al. Rosuvastatin reduces platelet activation in heart failure. Arterioscler Thromb Vasc Biol. 2005; 25:1071-1077.
Horwich T, Middlekauff H. Potential autonomic nervous system effects of statins in heart failure. Heart Fail Clin. 2008; 4: 163-170.
Tousoulis D, Antoniades C, Bosinakou E, Kotsopoulou M, Tsioufis C, Tentolouris C, et al. Effects of atorvastatin on reactive hyperaemia and the thrombosis – fibrinolysis system in patients with heart failure. Heart. 2005; 91:27-31.
Strey CH, Young JM, Lainchbury JH, Frampton CM, Nicholls MG, Richards AM, et al. Short-term statin treatment improves endothelial function and neurohormonal imbalance in normocholesterolaemic patients with non-ischaemic heart failure. Heart. 2006; 92:16031609.
Shanes JG, Minadeo KN, Moret A, Grover M, Tabaie SA. Statin therapy in heart failure: Prognostic effects and potential mechanisms. Am Heart J. 2007; 154: 617-623.
Bauersachs J, Galuppo P, Fraccarollo D, Christ M, Ertl G. Improvement of left ventricular remodeling and function by hydroxymethylglutaryl coenzyme A reductase inhibition with cerivastatin in rats with heart failure after myocardial infarction. Circulation. 2001; 104:982-985
Senthil V, Chen S, Tsybouleva N, Halder T, Naqueh SF, Willerson J, et al. Prevention of cardiac hypertrophy by atorvastatin in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circ Res. 2005; 97: 285-292.
KjesKshus J, Pedersen TR, Olsson AG, Faergeman A, Pyörälä K. The effects of simvastatin on the incidence of heart failure in patients with coronay heart disease. J Card Fail. 1997; 3:255-256.
Sacks FM, Pfeffer MA, Moye LA, Rouleau J, Rutherford J, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med.1996;335:1001- 1009.
Horwich T, MacLellan WR, Fonarow G. Statin therapy is associated with improved survival in ischemic and non-ischemic heart failure. J Am Coll Cardiol. 2004; 43:642-648.
Ray J, Gong Y, Sykora K. Statin use and survival outcomes in elderly patients with heart failure. Arch Intern Med. 2005; 165:62-67.
Go A, Lee W, Yang J, Lo J, Gurwitz J. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA. 2006; 296:2105-2111.
Foody JM, Shah R, Galusha D, Masoudi FA, Havranek EP, Krumholz HM. Statins and mortality among elderly patients hospitalizad with heart failure. Circulation. 2006; 113:1086-1092.
Ezekowitz J, McAlister F, Humphries K, Norris C, Tonelli M, Ghali W, et al. The association among renal insufficiency, pharmacotherapy, and outcomes in 6,427 patients with heart failure and coronary artery disease. J Am Coll Cardiol. 2004; 44: 1587-192.
Mozaffarian D, Nye R, Levy W. Statin therapy is associated with lower mortality among patients with severe heart failure. Am J Cardiol. 2004; 93:1124-1129.
Hognestad A., Dickstein K., Myhre E. Snappin S, Kjekshus J. OPTIMAAL Investigators. Effect of combined statin and beta-blocker treatment on one-year morbidity and mortality after acute myocardial infarction associated with heart failure. Am J Cardiol. 2004; 93. 603606.
Krum H, Bailey M, Meyer W, Verkenne P, Dargie H, Lechat P, et al. Impact of statin therapy on clinical outcomes in chronic heart failure patients according to beta-blocker use: results of CIBIS II. Cardiology. 2007; 108:28-34.
Krum H, Caretta E, Latini R, Maggioni AP, Anand I, Masson S, et al. Statins and symptomatic chronic systolic heart failure: a post-hoc analysis of 5010 patients enrolled in Val-HeFT. Int J Cardiol. 2007; 119:48-53.
Krum H, Ashton E, Reid C, Kalff V, Roger J, Amarena J, et al. Doubleblind, randomized, placebo-controlled study of high-dose HMG CoA reductase inhibitor therapy on ventricular remodeling, proinflammatory cytokines and neurohormonal parameters in patients with chronic systolic heart failure. J Card Fail. 2007; 13: 1-7.
Khush K, Waters D, Bittner D, Deedwania PC, Kastelein JJ, Lewis SJ, et al. Effect of high-dose atorvastatin on hospitalizations for heart failure. Subgroup analysis of the treating to new targets (TNT) study. Circulation. 2007; 115:576-583.
Kjieshus J, Apetrei E, Barrios V, Böhm M, Cleland J, Cornel J, et al. Rosuvastatin for older patients with systolic heart failure. N Engl J Med. 2007; 357:1-14.
Tavazzi L, Tognoni G, Franzosi MG, Latini R, Maggioni A, Marchioli R, et al.. Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure. Eur J Heart Fail. 2004; 6:635– 641.
GISSI-HF investigators. Effects of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomized, double-blind, placebo-controlled trial. Lancet. En: http://download.thelancet.com/ pdfs/journals/0140-6736/PIIS0140673608612404.pdf Consultado el 15 de setiembre de 2008.
Rauchhuss M, Coats AJ, Anker S. The endotoxin-lipoprotein hypothesis. Lancet. 2000; 356: 930-933.
Littarru GP, Langsjoen P. Coenzyme Q10 and statins: biochemical and clinical implications. Mithocondrion. 2007; S168-S174.
De Pinieux G. Lipid-lowering drugs and mithochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio. Br J Clin Pharmacol. 1996; 42:333-337.
van der Harst P, Voors A, van Gilst WH, Böhm M, van Veldhussein DJ. Statin in the treatment of chronic heart failure: biological and clinical consideration. Cardiovas Res. 2006; 443-454.
Afsarmanesh N, Horwich TB, Fonarow GC. Total cholesterol levels and mortality risk in nonischemic systolic heart failure. Am Heart J. 2006; 152; 1077-1083.
Horwich TB, Hamilton MA, Maclellan WR, Fonarow GC. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail. 2002; 8: 216-224.
Rauchhaus M, Clark AL, Doehner W, Davos C, Bolger A, Sharma R, et al. The relationship between cholesterol and survival in patients with chronic heart failure. J Am Coll Cardiol. 2003; 42: 1933-1940.
Ramasubbu K, Mann D. The emerging role of statins in the treatment of heart failure. J Am Coll Cardiol. 2006; 47: 342-344.
Mann D, McMurray J, Packer M, Swedberg K, Borer J, Colucci W, et al. Targeted anticytokine therapy in patients with chronic heart failure: results of the randomized etanercept worldwide evaluation. Circulation. 2004; 109: 1594-1602.
Ramasubbu K, Mann D. The emerging role of statins in the treatment of heart failure. J Am Coll Cardiol. 2006; 47: 342-344.
LIPID Study Group. Prevention of cardiovascular events with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998; 339: 1349-1357.
Downs JR, Clearfield M, Weis S, Whitney E, Shapiro D, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. JAMA. 1998; 279: 16151622.
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