cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLCcardiovascular-1520Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEW ARTICLESДвойное ингибирование холестерина — новый подход к эффективному контролю гиперлипидемии и атеросклерозаDouble cholesterol inhibition — a new approach to effective control of hyperlipidemia and atherosclerosisСусековА. В.SusekovA. V.

Старший научный сотрудник отдела возрастных проблем сердечно-сосудистых заболеваний.

Москва, тел.: (495) 414-69-92

Moscow

asus99@mail.ruГорняковаН. Б.GornyakovaN. B.

Младший научный сотрудник отдела.

Москва

Moscow

ЗубареваМ. Ю.ZubarevaM. Yu.

Младший научный сотрудник отдела.

Москва

Moscow

РожковаТ. А.RozhkovaT. A.

Научный сотрудник отдела.

Москва

Moscow

СоловьеваЕ. Ю.SolovyevaE. Yu.

Научный сотрудник отдела.

Москва

Moscow

Институт клинической кардиологии им А.Л. Мясникова ФГУ “РКНПК Росмедтехнологии”A.L. Myasnikov Research Institute of Clinical Cardiology, Russian Cardiology Scientific and Clinical Complex2009201220098698110Copyright © Сусеков А.В., Горнякова Н.Б., Зубарева М.Ю., Рожкова Т.А., Соловьева Е.Ю., 20092009Сусеков А.В., Горнякова Н.Б., Зубарева М.Ю., Рожкова Т.А., Соловьева Е.Ю.Susekov A.V., Gornyakova N.B., Zubareva M.Y., Rozhkova T.A., Solovyeva E.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/1520

Повышение уровня холестерина липопротеринов низкой плотности (ХС ЛНП) — один из основных факторов риска (ФР) ишемической болезни сердца и атеросклероза. Статины, имея убедительную доказательную базу по снижению смертности, являются основными препаратами для лечения больных с ате­росклерозом. Результаты контролируемых исследований последних лет по снижению ХС послужили обоснованием для снижения уровня целевых значений липидов: ХС ЛНП ≤ 2 ммоль/л. Двойное ингибирование ХС — новая концепция в снижении ХС плазмы крови до 50% за счет блокирования синтеза (статин) и уменьшения реабсорбции пищевого и билиарного ХС в тонком кишечнике. Клинические исследования препарата Инеджи® с фиксированной комбинацией (эзетимиб/симвастатин) показали высокую эффективность в достижении новых целевых уровней ХС ЛНП, а также хорошую переносимость и безопасность по сравнению с монотерапией статинами. Текущее клиническое исследование IMPROVE—IT с оценкой влияния двойного ингибирования на сердечно-сосудистую смертность позволит окончательно определить место эзетимиба и Инеджи® в лечении больных с дислипидемиями и атеросклерозом.

The increased level of low-density lipoprotein cholesterol (LDL-CH) is one of the risk factors (RFs) of coronary heart disease and atherosclerosis. Statins, with their vast evidence base on mortality reduction, are the principal medications in atherosclerosis treatment. The results of the recent controlled studies on CH reduction justified the decrease in target lipid levels: for LDL-CH — 2 mmol/l or less. Double CH inhibition is a new concept in plasma CH reduction by 50%, due to synthesis blockage (statins) and reduced intestinal reabsorption of dietary and biliary CH. The clinical trials of a fixed-dose combination Inegi ® (Ezetimibe / simvastatin) demonstrated its high effectiveness in achieving new target levels of LDL-CH, as well as good tolerability and safety, compared to statin monotherapy. The ongoing clinical trial IMPROVE-IT, assessing the effects of double CH inhibition on cardiovascular mortality, will clarify the role of Ezetimibe® and Inegi® in the treatment of dyslipidemia and atherosclerosis.

холестерин низкой плотностистатиныЭзетимибИнеджицелевые уровни ХС ЛНПэффективностьбезопасностьlow-density cholesterolstatinsEzetimibeInegitarget levels of low-density lipoprotein cholesteroleffectivenesssafetyReferencesYusuf S, Hawken S, Ounpuu S. at al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937-52.Yusuf S, Hawken S, Ounpuu S. at al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937-52.Shepherd J, Cobbe SM, Isles CG, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333: 1301-7.Shepherd J, Cobbe SM, Isles CG, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333: 1301-7.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 with average cholesterol levels. JAMA 1998; 279: 1615-22.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 with average cholesterol levels. JAMA 1998; 279: 1615-22.Sever PS, Dahlof B, Poulter NR, et al. 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 controlled lipid -lowering trial. Lancet 2003; 361: 1149-58.Sever PS, Dahlof B, Poulter NR, et al. 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 controlled lipid -lowering trial. Lancet 2003; 361: 1149-58.Colhoun HM, Betteridge DJ, Durrington PN, et al. Rapid emergence of effect of atorvastatin on cardiovascular outcomes in the Collaborative Atorvastatin Diabetes Study (CARDS). Diabetologia 2005; 48(12): 2482-5.Colhoun HM, Betteridge DJ, Durrington PN, et al. Rapid emergence of effect of atorvastatin on cardiovascular outcomes in the Collaborative Atorvastatin Diabetes Study (CARDS). Diabetologia 2005; 48(12): 2482-5.Ridker P, Danielson E, Fonseca FA, et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. N Engl J Med 2008; 359: 2195-207.Ridker P, Danielson E, Fonseca FA, et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. N Engl J Med 2008; 359: 2195-207.Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344:1383-9.Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344:1383-9.Sacks FN, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol level. N Engl J Med 1996; 335: 1001-9.Sacks FN, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol level. N Engl J Med 1996; 335: 1001-9.Heart Protection Collaborative Group. Effects of cholesterollowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004; 363: 757-67.Heart Protection Collaborative Group. Effects of cholesterollowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004; 363: 757-67.Cannon CP, Braunwald E, McCabe CH, et al. Pravastatin or Atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction 22 investigators. Intensive versus moderate lipid-lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350: 1495-504.Cannon CP, Braunwald E, McCabe CH, et al. Pravastatin or Atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction 22 investigators. Intensive versus moderate lipid-lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350: 1495-504.LaRosa JC, Grundy SM, Waters DD, et al. Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005; 352(14): 1425-35.LaRosa JC, Grundy SM, Waters DD, et al. Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005; 352(14): 1425-35.Pearson TA, Laurora I, Chu H, et al. The Lipid Treatment Assessment Project (L-TAP). A multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med 2000; 160: 459-67.Pearson TA, Laurora I, Chu H, et al. The Lipid Treatment Assessment Project (L-TAP). A multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med 2000; 160: 459-67.EUROASPIRE II Study Group. Lifestyle and risk factor management and use of drug therapies inn coronary patients from 15 countries. Principal results from EUROASPIRE II Euro Heart Survey Programm. Eur Heart J 2001; 22: 554-72.EUROASPIRE II Study Group. Lifestyle and risk factor management and use of drug therapies inn coronary patients from 15 countries. Principal results from EUROASPIRE II Euro Heart Survey Programm. Eur Heart J 2001; 22: 554-72.Kotseva K, Wood D, de Backer G, et al. Cardiovascular prevention guidelines in a daily practice: a comparison of EUROASPIRE I, II and III surveys in eight European countries. Lancet 2009; 14: 373(9667): 929-40.Kotseva K, Wood D, de Backer G, et al. Cardiovascular prevention guidelines in a daily practice: a comparison of EUROASPIRE I, II and III surveys in eight European countries. Lancet 2009; 14: 373(9667): 929-40.Kotseva K, Wood D, de Backer G, et al. EUROASPIRE III: a survey on the lifestyle, risk factors and use of cardiovascular drug therapies in coronary patients from 22 European countries. Eur J Cardiovasc Prev Rehabil 2009; 16(2): 121-37.Kotseva K, Wood D, de Backer G, et al. EUROASPIRE III: a survey on the lifestyle, risk factors and use of cardiovascular drug therapies in coronary patients from 22 European countries. Eur J Cardiovasc Prev Rehabil 2009; 16(2): 121-37.Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285(19): 2486-97.Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285(19): 2486-97.Grundy SM, Cleeman JI, Bairey CN, et al. Implication of Recent Clinical Trials for the National Cholesterol Education Programm Adult Treatment Panel III Guidelines. Circulation 2004; 110: 227-39.Grundy SM, Cleeman JI, Bairey CN, et al. Implication of Recent Clinical Trials for the National Cholesterol Education Programm Adult Treatment Panel III Guidelines. Circulation 2004; 110: 227-39.Smith S, Allen J, Blair S, et al. AHA/ACC Guidelines for Secondary Prevention for Patients with coronary and other atherosclerotic Vascular Disease: 2006 Update. Circulation 2006; 113: 2363-72.Smith S, Allen J, Blair S, et al. AHA/ACC Guidelines for Secondary Prevention for Patients with coronary and other atherosclerotic Vascular Disease: 2006 Update. Circulation 2006; 113: 2363-72.www.escario.orgwww.escario.orgДиагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации. Кардиоваск тер профил 2007; 6(Приложение 3): 3-26.Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации. Кардиоваск тер профил 2007; 6(Приложение 3): 3-26.Goettsch WG, Yin DD, Alemao E, et al. Statins are less effective in common daily practice among patients with hypercholesterolaemia: the REALITY-PHARMO study. Curr Med Res Opin 2004; 20(7): 1025-33.Goettsch WG, Yin DD, Alemao E, et al. Statins are less effective in common daily practice among patients with hypercholesterolaemia: the REALITY-PHARMO study. Curr Med Res Opin 2004; 20(7): 1025-33.Ganse EV, Laforest L, Alemao E, et al. Lipid-modifying therapy and attainment of cholesterol goals in Europe: the Return on Expenditure Achieved for Lipid Therapy (REALITY) study. Curr Med Res Opin 2005; 21(9): 1389¬99.Ganse EV, Laforest L, Alemao E, et al. Lipid-modifying therapy and attainment of cholesterol goals in Europe: the Return on Expenditure Achieved for Lipid Therapy (REALITY) study. Curr Med Res Opin 2005; 21(9): 1389¬99.Cesari M, Maiolino G, Colonna S, et al. Under treatment with lipid-lowering drugs of high-risk coronary heart disease patients of the GENICA study. J Cardiovasc Pharmacology 2003; 42(4): 484-90.Cesari M, Maiolino G, Colonna S, et al. Under treatment with lipid-lowering drugs of high-risk coronary heart disease patients of the GENICA study. J Cardiovasc Pharmacology 2003; 42(4): 484-90.Harats D, Leibovitz E, Maislos M, et al. Cardiovascular risk assessment and treatment to target low density lipoprotein levels in hospitalized ischemic heart disease patients: results of the HOLEM study. Isr Med Assoc J 2005; 7(8): 355-9.Harats D, Leibovitz E, Maislos M, et al. Cardiovascular risk assessment and treatment to target low density lipoprotein levels in hospitalized ischemic heart disease patients: results of the HOLEM study. Isr Med Assoc J 2005; 7(8): 355-9.Rondina MT, Zebrack JS. Achieving. National Cholesterol Education Program goals in coronary artery disease. Prev Cardiol 2005; 8(1): 18-22.Rondina MT, Zebrack JS. Achieving. National Cholesterol Education Program goals in coronary artery disease. Prev Cardiol 2005; 8(1): 18-22.Van Ganse E, Souchet T, Laforest L, et al. Ineffectiveness of lipid-lowering therapy in primary care. Br J Clin Pharmacol 2005; 59(4): 456-63.Van Ganse E, Souchet T, Laforest L, et al. Ineffectiveness of lipid-lowering therapy in primary care. Br J Clin Pharmacol 2005; 59(4): 456-63.Сусеков А.В., Зубарева М.Ю, Деев А Д и др. Основные результаты Московского Исследования по Статинам. Сердце 2006; 5(6): 324-8.Сусеков А.В., Зубарева М.Ю, Деев А Д и др. Основные результаты Московского Исследования по Статинам. Сердце 2006; 5(6): 324-8.Andrade SE, Walker AM, Gottlieb LK, et al. Discontinuation of antihyperlipidemic drugs— do rates reported in clinical trials reflect rates in primary care settings? N Engl J Med 1995; 332(17): 1125-31.Andrade SE, Walker AM, Gottlieb LK, et al. Discontinuation of antihyperlipidemic drugs— do rates reported in clinical trials reflect rates in primary care settings? N Engl J Med 1995; 332(17): 1125-31.Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 2002; 288: 462-7.Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 2002; 288: 462-7.Larsen J, Andersen M, Kragstrup J, et al. High persistence of statin use in Danish population: compliance study 1993— 1998. Br J Clin Pharmacology 2002; 53: 375-8.Larsen J, Andersen M, Kragstrup J, et al. High persistence of statin use in Danish population: compliance study 1993— 1998. Br J Clin Pharmacology 2002; 53: 375-8.Riesen WF, Darioli R, Noll G. Lipid-lowering therapy: strategies for improving Compliance. Curr Med Res Opin 2004; 20(2): 165-73.Riesen WF, Darioli R, Noll G. Lipid-lowering therapy: strategies for improving Compliance. Curr Med Res Opin 2004; 20(2): 165-73.Avorn J, Monette J, Lacour A, et al. Persistance of the use of lipid-Lowering edications: a cross-national study. JAMA 1998; 279: 1458-62.Avorn J, Monette J, Lacour A, et al. Persistance of the use of lipid-Lowering edications: a cross-national study. JAMA 1998; 279: 1458-62.Erhardt L. Are we treating to targets? Atherosclerosis 2000; Suppl. 1: 9-14.Erhardt L. Are we treating to targets? Atherosclerosis 2000; Suppl. 1: 9-14.Hibble A, Kanka S, Pencheon D, et al. Guidelines in general practice: the New Tower of bibel? Br Med J 1998; 317(7162): 862-3.Hibble A, Kanka S, Pencheon D, et al. Guidelines in general practice: the New Tower of bibel? Br Med J 1998; 317(7162): 862-3.Thompson GR, O’Neal F, Seed M. Why same patients respond poorly to stains and how this might be remedied. Eur Heart J 2002; 23(3): 200-6.Thompson GR, O’Neal F, Seed M. Why same patients respond poorly to stains and how this might be remedied. Eur Heart J 2002; 23(3): 200-6.Bruckert E, Simonetta C, Giral P. Compliance with fluvastatin treatment characterization of the noncompliant population within of population of 3845 patients with hyperlipidaemia. CREOLE Study Team. J Clin Epidemiol 1999; 52: 589-94.Bruckert E, Simonetta C, Giral P. Compliance with fluvastatin treatment characterization of the noncompliant population within of population of 3845 patients with hyperlipidaemia. CREOLE Study Team. J Clin Epidemiol 1999; 52: 589-94.Williams D, Feely J. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin Pharmacokinet 2002; 41: 343-70.Williams D, Feely J. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin Pharmacokinet 2002; 41: 343-70.Simons LA, Levis G, Simons J. Apparent discontinuation rates in patients Prescribed lipid-lowering drugs. Med J Aust 1996; 164: 208-11.Simons LA, Levis G, Simons J. Apparent discontinuation rates in patients Prescribed lipid-lowering drugs. Med J Aust 1996; 164: 208-11.Roberts WC. The rule of 5 and the rule of 7 in lipid-lowering by statin drugs. Am J Cardiol 1997; 80: 106-7.Roberts WC. The rule of 5 and the rule of 7 in lipid-lowering by statin drugs. Am J Cardiol 1997; 80: 106-7.Silva M, Matthews ML, Jarvis C, et al. Meta-analysis of drug- induced adverse events associated with intensive-dose statin therapy. Clin Ther 2007; 29(2): 253-60.Silva M, Matthews ML, Jarvis C, et al. Meta-analysis of drug- induced adverse events associated with intensive-dose statin therapy. Clin Ther 2007; 29(2): 253-60.Turley SD. Dietary cholesterol and mechanisms of cholesterol absorption. Eur Heart J 1999; 1(Suppl. S): S29-35.Turley SD. Dietary cholesterol and mechanisms of cholesterol absorption. Eur Heart J 1999; 1(Suppl. S): S29-35.Thompson GR, O’Neal F, Seed M. Why same patients respond poorly to stains and how this might be remedied. Eur Heart J 2002; 23(3): 200-6.Thompson GR, O’Neal F, Seed M. Why same patients respond poorly to stains and how this might be remedied. Eur Heart J 2002; 23(3): 200-6.Dietschy JM. Theoretical considerations of what regulates low- density-lipoprotein and igh-density-lipoprotein cholesterol. Am J Clin Nutr 1997; 65(Suppl): 1581S-9.Dietschy JM. Theoretical considerations of what regulates low- density-lipoprotein and igh-density-lipoprotein cholesterol. Am J Clin Nutr 1997; 65(Suppl): 1581S-9.Van Heek M, France CF, Compton DS, et al. In vivo metabolism-based discovery of a potent cholesterol-absorption inhibitor, SCH 58235, in the rat and rhesus monkey through the identification of the active metabolites of SCH48461. J Pharmacol Exp Ther 1997; 283: 157-63.Van Heek M, France CF, Compton DS, et al. In vivo metabolism-based discovery of a potent cholesterol-absorption inhibitor, SCH 58235, in the rat and rhesus monkey through the identification of the active metabolites of SCH48461. J Pharmacol Exp Ther 1997; 283: 157-63.Bays HE, Moore PB, Drehobl MA, et al. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Clin Ther 2001; 23(9): 1209-30.Bays HE, Moore PB, Drehobl MA, et al. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Clin Ther 2001; 23(9): 1209-30.Stone N, Blum C, Winslow E. Management of Lipids in Clinical Practice. Professional Communications Inc 1997; 178.Stone N, Blum C, Winslow E. Management of Lipids in Clinical Practice. Professional Communications Inc 1997; 178.Сусеков А.В. Эзетимиб, ингибитор абсорбции холестерина: новые возможности в лечении дислипидемий и атеросклероза. Тер архив 2005; 77(8): 24-9.Сусеков А.В. Эзетимиб, ингибитор абсорбции холестерина: новые возможности в лечении дислипидемий и атеросклероза. Тер архив 2005; 77(8): 24-9.Сусеков А.В., Зубарева М.Ю., Кухарчук В.В. Результаты наблюдательной программы по эзетролу "Исследование двух столиц". Фарматека 2006; 8: 65-70.Сусеков А.В., Зубарева М.Ю., Кухарчук В.В. Результаты наблюдательной программы по эзетролу "Исследование двух столиц". Фарматека 2006; 8: 65-70.Davidson MN, McGarry T, Bettis R, et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolaemia. JACC 2002; 40: 2125-34.Davidson MN, McGarry T, Bettis R, et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolaemia. JACC 2002; 40: 2125-34.Gagner C, Bays H, Weiss SR, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolaemia. Am J Cardiol 90(10): 1084-91.Gagner C, Bays H, Weiss SR, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolaemia. Am J Cardiol 90(10): 1084-91.Ballantyne C, Abate N, Yuan Z, et al. Dose comparison study of combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolaemia: The Vytorin Versus Atorvastatin (VYVA) Study. Am Heart J 2005; 149: 464-73.Ballantyne C, Abate N, Yuan Z, et al. Dose comparison study of combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolaemia: The Vytorin Versus Atorvastatin (VYVA) Study. Am Heart J 2005; 149: 464-73.Catapano A, Davidson M, Ballantyne CM, et al. Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvasatin in hypercholesterolemic patients. Curr Med Res Opin 2006; 22: 1-13.Catapano A, Davidson M, Ballantyne CM, et al. Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvasatin in hypercholesterolemic patients. Curr Med Res Opin 2006; 22: 1-13.Catapano A, Brady W, King T, et al. Lipid altering-efficacy of ezetimibe co-administered with simvastatin compared with rosuvastatin: a meta-analysis of pooled data from 14 clinical trials. Curr Med Res Opin 2005; 21:(7): 1123-30.Catapano A, Brady W, King T, et al. Lipid altering-efficacy of ezetimibe co-administered with simvastatin compared with rosuvastatin: a meta-analysis of pooled data from 14 clinical trials. Curr Med Res Opin 2005; 21:(7): 1123-30.Farnier M, Averna M, Missault L, et al. Lipid-altering efficacy of ezetimibe/simvstatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesteroaemic patients inadequately controlled with prior statin monotherapy- The IN-CROSS study. Intern J Clin 2009; 63(4): 547-59.Farnier M, Averna M, Missault L, et al. Lipid-altering efficacy of ezetimibe/simvstatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesteroaemic patients inadequately controlled with prior statin monotherapy- The IN-CROSS study. Intern J Clin 2009; 63(4): 547-59.Davidson MH, Abate N, Ballantyne C, et al. Ezetimibe/ simvastatin compared with atorvastatin or rosuvastatin in lowering to specified levels both LDL-C and each of five other emerging risk factors for coronary heart disease: non-HDL-cholesterol, TC/HDL-C, apolipoprotein B, apo B/apo A-I, or C-reactive protein. J Clin Lipid 2008; 2: 436-46.Davidson MH, Abate N, Ballantyne C, et al. Ezetimibe/ simvastatin compared with atorvastatin or rosuvastatin in lowering to specified levels both LDL-C and each of five other emerging risk factors for coronary heart disease: non-HDL-cholesterol, TC/HDL-C, apolipoprotein B, apo B/apo A-I, or C-reactive protein. J Clin Lipid 2008; 2: 436-46.Robinson J, Ballantyne C M, Grundy S, et al. Lipid-altering efficacy and Safety of ezetimibe/Simvastatin versus Atrorvastatin in patients with hypercholesterolemia and the Metabolic Syndrome (from the VYMET Study). Am J Cardiol 2009; 103: 1694-702.Robinson J, Ballantyne C M, Grundy S, et al. Lipid-altering efficacy and Safety of ezetimibe/Simvastatin versus Atrorvastatin in patients with hypercholesterolemia and the Metabolic Syndrome (from the VYMET Study). Am J Cardiol 2009; 103: 1694-702.Winkler K, Schewe T, Putz G, et al. Fluvastatin/fenofibrate vs. Simvstatin/ezetimibe in patients with metabolic syndrome: different effects on LDL-profiles. Eur J Clin Investigation 2009; 39(6): 463-70.Winkler K, Schewe T, Putz G, et al. Fluvastatin/fenofibrate vs. Simvstatin/ezetimibe in patients with metabolic syndrome: different effects on LDL-profiles. Eur J Clin Investigation 2009; 39(6): 463-70.Farnier M, Roth E, Gil-Extremera, et al. Efficacy and safety of the co-administration of ezetimibe/simvastatin with fenofibrate in patients with mixed hyperlipideamia. Am Heart J 2007; 153(2): 335-e1-8.Farnier M, Roth E, Gil-Extremera, et al. Efficacy and safety of the co-administration of ezetimibe/simvastatin with fenofibrate in patients with mixed hyperlipideamia. Am Heart J 2007; 153(2): 335-e1-8.Kastelein J, Akdim F, Stroes E, et al. Simvastatin with or without ezetimibe in Familial Hypercholesterolaemia. N Engl J Med 2008; 358: 1431-43.Kastelein J, Akdim F, Stroes E, et al. Simvastatin with or without ezetimibe in Familial Hypercholesterolaemia. N Engl J Med 2008; 358: 1431-43.Rossebo A, Pedersen T, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenoisis. N Engl J Med 2008; 359: 1-14.Rossebo A, Pedersen T, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenoisis. N Engl J Med 2008; 359: 1-14.Fleg JL, Mete M, Howard B, et al. Effect of Statins alone versus statin plus ezetimibe on carotid atherosclerosis in type 2 diabetes. JACC 2008; 521-8.Fleg JL, Mete M, Howard B, et al. Effect of Statins alone versus statin plus ezetimibe on carotid atherosclerosis in type 2 diabetes. JACC 2008; 521-8.Crouse JR, Frohlich J, Ose L, Mercuri M, et al. Effects of high doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I. Am J Cardiol 1999; 83(10): 1476-7, A7.Crouse JR, Frohlich J, Ose L, Mercuri M, et al. Effects of high doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I. Am J Cardiol 1999; 83(10): 1476-7, A7.

The authors declare that there are no conflicts of interest present.