Views
4 years ago

16 - JL Cacharrón - Mayo de 2012

  • Text
  • Nota
  • Cardio
  • Atherosclerosis
  • Ancianos
  • Dosis
  • Tratamiento
  • Efectos
  • Colesterol
  • Coronary
  • Cholesterol
  • Pacientes
  • Estatinas
Uso racional de fármacos hipolipemiantes en el adulto mayor (Segunda parte)

cian con el tratamiento

cian con el tratamiento de la dislipidemia, sino que no presentan más efectos adversos que las personas jóvenes. Además, la reducción de riesgo relativo para eventos coronarios y la mortalidad, es mayor en los pacientes de este grupo etario. El NNT (número necesario a tratar) para prevenir eventos cardiovasculares es menor en los ancianos que en los jóvenes, lo que refleja el mayor riesgo de padecer estos eventos en esta población. No hay estudios aleatorios y controlados con estatinas en los pacientes muy ancianos, sin embargo, en estudios observacionales, en prevención secundaria, se ha demostrado una reducción de la mortalidad en los ancianos tratados con estatinas. Las metas de LDL se han ido reduciendo a medida que se demostró mayor beneficio con los tratamientos más agresivos. Aunque no se han realizado trabajos sobre estos tratamientos con estatinas a altas dosis en ancianos de alto riesgo, no hay motivos para sospechar que estos pacientes no responderían de igual manera que los pacientes jóvenes. Hay que destacar que todos estos estudios fueron realizados en pacientes con enfermedad coronaria o de alto riesgo. Por su parte, el rol del tratamiento hipolipemiante como prevención primaria en ancianos no ha sido estudiado en trabajos controlados y aleatorizados. El ezetimibe es una droga que inhibe la absorción del colesterol a nivel gastrointestinal. El tratamiento combinado con ezetimibe y estatinas produce una mayor reducción del colesterol, permitiendo que se utilicen dosis más bajas de estatinas. En estudios que incluyen a pacientes ancianos, se ha evidenciado que este tratamiento produce un descenso significativo del colesterol en este grupo de pacientes, comparable a los que se evidencia en pacientes jóvenes, sin que se presenten más efectos adversos que los pacientes tratados solamente con estatinas. En los trabajos en que se analiza el tratamiento combinado con estatinas y fibratos, hay pocos que incluyen pacientes mayores de 65 años. En general, los autores sugieren que la edad, sexo femenino, enfermedad renal o hepática, diabetes, hipotiroidismo, mal estado general, alcoholismo, cirugía, traumatismo y ejercicio intenso aumentarían el riesgo de miopatía. Sin embargo, en la mayoría de los trabajos controlados y aleatorizados con esta combinación de drogas, se ha demostrado una reducción significativa del colesterol total y de los triglicéridos, un aumento del colesterol HDL, con escasos efectos adversos importantes. No obstante a los ancianos a los que se indicó tratamiento combinado presentaron más efectos adversos que los pacientes más jóvenes. En los estudios realizados con fibratos, se demostró una reducción significativa del colesterol total y triglicéridos, y una reducción más variable en el colesterol LDL, en general, asociado aun aumento del colesterol HDL. Con estas drogas, se ha demostrado una reducción significativa de eventos cardiovasculares. En conclusión, el riesgo de enfermedad cardiovascular y cerebrovascular en pacientes mayores de 65 años es considerablemente mayor que en los más jóvenes. Los tratamientos no farmacológicos han demostrado ser beneficiosos en ancianos. Los pacientes ancianos con riesgo cardiovascular deberían ser tratados con drogas hipolipemiantes, particularmente, estatinas. En los pacientes muy ancianos -mayores de 75 años-, ancianos frágiles, ancianos con comorbilidades, especialmente enfermedad renal o hepática, es fundamental el criterio clínico para evaluar los riesgos y beneficios del tratamiento. Actualmente, no hay evidencia sobre el tratamiento hipolipemiante en ancianos de riesgo leve o moderado en cuanto a la prevención primaria. Bibliografía sugerida 1. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials.JAMA. 1999 Dec 22- 29;282(24):2340-6. LaRosa JC, He J, Vupputuri S. 2. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002 Jul 6;360(9326):23-33. 2. Pitt B, Mancini GBJ, Ellis SG, et al, for the PLAC I Investigators. Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC I): Reduction in atherosclerosis progression and clinical events. J Am Coll Cardiol 26:1133-1139, 1995. 3. Byington RP, Jukema JW, Salonen JT, et al: Reduction in cardiovascular events during pravastatin therapy: Pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention Program. Circulation 92:2419-2425, 1995. 4. Blankenhorn DH, Azen SP, Kramsch DM, et al, and the MARS Research Group: Coronary angiographic changes with lovastatin therapy: The Monitored Atherosclerosis Regression Study (MARS). Ann Intern Med 119:969-976, 1993. 5. Herd JA, Ballantyne CM, Farmer JA, et al, for the LCAS Investigators: Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]). Am J Cardiol 80:278-286, 1997. 6. Sacks FM, Pasternak RC, Gibson CM, et al, for the Harvard Atherosclerosis Reversibility Project (HARP) Group: Effect on coronary atherosclerosis of decrease in plasma cholesterol concentrations in normocholesterolaemic patients. Lancet 344:1182-1186, 1994. 7. Pasternak RC, Brown LE, Stone PH, et al: Effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and "normal" cholesterol levels: A randomized, placebo-controlled trial. Harvard Atherosclerosis Reversibility Project (HARP) Study Group. Ann Intern Med 125:529-540, 1996. 8. Sacks FM, Gibson CM, Rosner B, et al: The influence of pretreatment low density lipoprotein cholesterol concentrations on the effect of hypocholesterolemic therapy on coronary atherosclerosis in angiographic trials. Harvard Atherosclerosis Reversibility Project Research Group. Am J Cardiol 76(9):78C-85C, 1995. 9. Furberg CD, Adams HP Jr, Applegate WB, et al, for the Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group: Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Circulation 90:1679- 1687, 1994. 10. Espeland MA, Applegate W, Furberg CD, et al: Estrogen replacement therapy and progression of intimal-medial thickness in the carotid arteries of postmenopausal women. ACAPS Investigators. Asymptomatic Carotid Atherosclerosis Progression Study. Am J Epidemiol 142:1011-1019, 1995. 11. Salonen R, Nyyssonen K, Porkkala E, et al: Kuopio Atherosclerosis Prevention Study (KAPS): A populationbased primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circulation 92:1758-1764, 1995. 12.. Downs JR, Clearfield M, Weis S, et al, for the AFCAPS/TexCAPS Research Group: Primary prevention of acute coronary events with lovastatin in men and women 12 | Editorial Sciens

farmacología cardiovascular 16 | Mayo de 2012 with average cholesterol levels: Results of AFCAPS/TexCAPS. JAMA 279:1615-1622, 1998. 13. Shepherd J, Cobbe SM, Ford I, et al, for the West of Scotland Coronary Prevention Study Group: Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 333:1301-1307, 1995. 14. Caro J, Klittich W, McGuire A, et al: The West of Scotland coronary prevention study: Economic benefit analysis of primary prevention with pravastatin. BMJ 315:1577-1582, 1997. 15. Sacks FM, Pfeffer MA, Moye LA, et al, for the Cholesterol and Recurrent Events Trial Investigators: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 335:1001-1009, 1996. 16. Pfeffer MA, Sacks FM, Moye LA, et al: Influence of baseline lipids on effectiveness of pravastatin in the CARE Trial. Cholesterol and Recurrent Events. J Am Coll Cardiol 33:125-130, 1999. 17. Goldberg RB, Mellies MJ, Sacks FM, et al: Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: Subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators. Circulation 98:2513-2519, 1998. 18. Lewis SJ, Moye LA, Sacks FM, et al: Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range: Results of the Cholesterol and Recurrent Events (CARE) trial. Ann Intern Med 129:681-689, 1998. 19. Lewis SJ, Sacks FM, Mitchell JS, et al: Effect of pravastatin on cardiovascular events in women after myocardial infarction: The cholesterol and recurrent events (CARE) trial. J Am Coll Cardiol 32:140-146, 1998. 20. Plehn JF, Davis BR, Sacks FM, et al: Reduction of stroke incidence after myocardial infarction with pravastatin: The Cholesterol and Recurrent Events (CARE) study. The CARE Investigators. Circulation 99:216-223, 1999. 21. Ridker PM, Rifai N, Pfeffer MA, et al: Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation 98:839-844, 1998. 22.. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group: Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 339:1349-1357, 1998. 23. Scandinavian Simvastatin Survival Study Group: Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S). Lancet 344:1383-1389, 1994. 24. Miettinen TA, Pyorala K, Olsson AG, et al: Cholesterollowering therapy in women and elderly patients with myocardial infarction or angina pectoris: Findings from the Scandinavian Simvastatin Survival Study (4S). Circulation 96:4211-4218, 1997. 25. Pedersen TR, Kjekshus J, Pyorala K, et al: Effect of simvastatin on ischemic signs and symptoms in the Scandinavian Simvastatin Survival Study (4S). Am J Cardiol 81:333-335, 1998. 26. Berg K, Dahlen G, Christophersen B, et al: Lp(a) lipoprotein level predicts survival and major coronary events in the Scandinavian Simvastatin Survival Study. Clin Genet 52:254-261, 1997. 27. Pitt B, Waters D, Brown WV, et al, for the Atorvastatin versus Revascularization Treatment Investigators. Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. N Engl J Med 341:70-76, 1999. 28. RITA-2 trial participants: Coronary angioplasty versus medical therapy for angina: The second Randomised Intervention Treatment of Angina (RITA-2) trial. Lancet 350:461-468, 1997. 29. Kumana CR, Cheung BMY, Lauder IJ: Gauging the impact of statins using number needed to treat. JAMA 282:1899-1901, 1999. 30. Prosser LA, Stinnett AA, Goldman PA, et al: Cost effectiveness of cholesterol-lowering therapies according to selected patient characteristics. Ann Intern Med 132:769- 779, 2000. 31. Feely J, McGettigan P, Kelly A: Growth in use of statins after trials is not targeted to most appropriate patients. Clin Pharmacol Ther 67:438-441, 2000. 32. Wood D, De Backer G, Faergeman O, et al: Prevention of coronary heart disease in clinical practice: Recommendations of the Second Joint Task Force of European and Other Societies on Coronary Prevention. Atherosclerosis 140:199-270, 1998. 33. West of Scotland Coronary Prevention Study Group: Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation 97:1440-1445, 1998. 34. Cohen JD, Drury JH, Ostdick J, et al: Benefits of lipid lowering on vascular reactivity in patients with coronary artery disease and average cholesterol levels: A mechanism for reducing clinical events? Am Heart J 139:734-738, 2000. 35. Gotto AM Jr: Statin therapy and reduced incidence of stroke. Implications of cholesterol-lowering therapy for cerebrovascular disease. Arch Intern Med 157:1283-1284, 1997. 36. Sacks FM, Moye LA, Davis BR, et al: Relationship between plasma LDL concentrations during treatment with pravastatin and recurrent coronary events in the Cholesterol and Recurrent Events trial. Circulation 97:1446-52, 1998. 37. Zheng Zhou, Elham Rahme et al. Effectiveness of statins for secondary prevention in elderly patients after acute myocardial infarction: an evaluation of class effect.CMAJ. 2005 April 26; 172(9): 1187–1194 38. Pedersen TR, Olsson AR, Faergeman O, et al, for the Scandinavian Simvastatin Survival Study Group: Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation 97:1453-1460, 1998. 39. Grundy SM: Statin trials and goals of cholesterol-lowering therapy. Circulation 97:1436-1439, 1998. 40. Gotto AM, Whitney E, Stein EA, et al: Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation 101:477-484, 2000. 41. Jukema JW, Bruschke AV, van Boven AJ, Reiber JH, Bal ET, Zwinderman AH, Jansen H, Boerma GJ, van Rappard FM, Lie KI, et al. Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS). Circulation. 1995 May 15;91(10):2528-40. 42. National Cholesterol Education Program Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) 43. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR, Leslie S, Stern T. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001 Apr 4;285(13):1711-8. 44. Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J; ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo- Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003 Apr 5;361(9364):1149-58. 45. Shannon J, Tewoderos S, Garzotto M; et al. Statins and prostate cancer risk: a case-control study. Am J Epidemiol 2005; 162: 318-325. 46. Vaughan Carl, Murphy Michael and Buckley Brenda. Statins do more than just lower cholesterol. Lancet 1996; 348: 1079-1082. 47. Sarkar Kunal, Anjan k; Sinha and jawahar L Metha. The role of statins in endothelial dysfuncyon in hypertension. Current Opinion in Cardioplogy 2005; 21: 316-321. 48. Maron David, Fazio Sergio; McRae F; et al. Current perspectiva on statins. Circulation 2000; 101:207-213. 49. Schuster H, Barter PJ, Stender S, Cheung RC, Bonnet J, Morrell JM, Watkins C, Kallend D, Raza A; Effective Reductions in Cholesterol Using Rosuvastatin Therapy I study group. Effects of switching statins on achievement of lipid goals: Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study. Am Heart J. 2004 Apr;147(4):705-13. 50. Gray Jhanelle, Alberts Michael and Bepler Gerold. Statins and lung cancer risk. Chest 2007; 131 : 1274-1275. 51. Ballantyne CM, Bertolami M, Hernandez Garcia HR, Nul D, Stein EA, Theroux P, Weiss R, Cain VA, Raichlen JSAchieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target levels in high-risk patients: Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY (MERCURY) II. Am Heart J. 2006 May;151(5):975.e1-9. 52. Ballantyne CM, Abate N, Yuan Z, King TR, Palmisano J. Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: the Vytorin Versus Atorvastatin (VYVA) study. Am Heart J. 2005 Mar;149(3):464-73. Erratum in: Am Heart J. 2005 May;149(5):882. 53. Ansquer JC, Bekaert I, Guy M, Hanefeld M, Simon A. Efficacy and safety of coadministration of fenofibrate and ezetimibe compared with each as monotherapy in patients with type IIb dyslipidemia and features of the metabolic syndrome: a prospective, randomized, double-blind, three-parallel arm, multicenter, comparative study. Am J Cardiovasc Drugs. 2009;9(2):91-101. 54. Alawi A. Alsheikh-Ali, MD, Thomas A. Trikalinos, MD, David M. Kent, MD, MS, Richard H. Karas, MD, PHD. Statins, Low-Density Lipoprotein Cholesterol, and Risk of Cancer. J Am Coll Cardiol.2008;52(14):1141-1147. 55. John J.P. Kastelein, M.D., Ph.D., Fatima Akdim, M.D., Erik S.G. Stroes, M.D., Ph.D., Aeilko H. Zwinderman, Ph.D., Michiel L. Bots, M.D., Ph.D., Anton F.H. Stalenhoef, M.D., Ph.D., F.R.C.P., Frank L.J. Visseren, M.D., Ph.D., Eric J.G. Sijbrands, M.D., Ph.D., Mieke D. Trip, M.D., Ph.D., Evan A. Stein, M.D., Ph.D., Daniel Gaudet, M.D., Ph.D., Raphael Duivenvoorden, M.D., Enrico P. Veltri, M.D., A. David Marais, M.D., Ph.D., Eric de Groot, M.D., Ph.D., for the ENHANCE Investigators. Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia. NEJM 2008. 358:1431-1443. 56. Anne B. Rossebo, M.D., Terje R. Pedersen, M.D., Ph.D., Kurt Boman, M.D., Ph.D., Philippe Brudi, M.D., John B. Chambers, M.D., Kenneth Egstrup, M.D., Ph.D., Eva Gerdts, M.D., Ph.D., Christa Gohlke-Bärwolf, M.D., Ingar Holme, Ph.D., Y. Antero Kesäniemi, M.D., Ph.D., William Malbecq, Ph.D., Christoph A. Nienaber, M.D., Ph.D., Simon Ray, M.D., Terje Skjærpe, M.D., Ph.D., Kristian Wachtell, M.D., Ph.D., Ronnie Willenheimer, M.D., Ph.D., for the SEAS Investigators. Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis. NEJM 2008. 359:1343-1356. 57. Fleg JL, Mete M, Howard BV, Umans JG, Roman MJ, Ratner RE, Silverman A, Galloway JM, Henderson JA, Weir MR, Wilson C, Stylianou M, Howard WJ. Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial. Am Coll Cardiol. 2008 Dec 16;52(25):2198-205. 58. Pandor A, Ara RM, Tumur I, Wilkinson AJ, Paisley S, Duenas A, Durrington PN, Chilcott J. Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med. 2009 May;265(5):568-80. 59. Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R. Analyses of cancer data from three ezetimibe trials. N Engl J Med. 2008 Sep 25;359(13):1357-66. 60. Drazen JM, D'Agostino RB, Ware JH, Morrissey S, Curfman GD. Ezetimibe and cancer--an uncertain association. N Engl J Med. 2008 Sep 25;359(13):1398-9. Editorial. Editorial Sciens | 13

Biblioteca

Av. García del Río 2585 Piso 12 A - C.A.B.A
+54 11 2092 1646 | info@sciens.com.ar

Editorial Sciens, Todos los Derechos Reservados 2015