289
Views
13
CrossRef citations to date
0
Altmetric
Reviews

Emerging options in the treatment of dyslipidemias: a bright future?

, , & , MD FASA FRSH
Pages 247-270 | Published online: 15 Feb 2011

Bibliography

  • NHLBI. High blood cholesterol: what you need to know. Available from: http://www.nhlbi.nih.gov/health/public/heart/chol/wyntk.htm. [Accessed 10 December 2010]
  • WHO. Cardiovascular disease: prevention and control. Available from: http://www.who.int/dietphysicalactivity/publications/facts/riskfactors/en/index.html [Accessed 10 December 2010]
  • Baigent C, Keech A, Kearney PM, Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366(9493):1267-78
  • El Harchaoui K, Akdim F, Stroes ES, Current and future pharmacologic options for the management of patients unable to achieve low-density lipoprotein-cholesterol goals with statins. Am J Cardiovasc Drugs 2008;8(4):233-42
  • Barter P, Gotto AM, LaRosa JC, HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007;357(13):1301-10
  • Drexel H. Statins, fibrates, nicotinic acid, cholesterol absorption inhibitors, anion-exchange resins, omega-3 fatty acids: which drugs for which patients? Fundam Clin Pharmacol 2009;23(6):687-92
  • Barter PJ, Caulfield M, Eriksson M, Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007;357(21):2109-22
  • Nissen SE, Tardif JC, Nicholls SJ, Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med 2007;356(13):1304-16
  • Kastelein JJ, Akdim F, Stroes ES, Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008;358(14):1431-43
  • Bots ML, Visseren FL, Evans GW, Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. Lancet 2007;370(9582):153-60
  • Bhatt DL, Steg PG, Ohman EM, International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 2006;295(2):180-9
  • American Heart Association. Heart Disease and Stroke Statistics 2010 Update. Available from: http://www.americanheart.org/downloadable/heart/1265665152970DS-3241%20HeartStrokeUpdate_2010.pdf [Accessed 10 December 2010]
  • LaRosa JC, Grundy SM, Waters DD, Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352(14):1425-35
  • Colhoun HM, Betteridge DJ, Durrington PN, Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364(9435):685-96
  • Heart Protection Study Collaborative group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360(9326):7-22
  • Kotseva K, Wood D, De Backer G, EUROASPIRE III. Management of cardiovascular risk factors in asymptomatic high-risk patients in general practice: cross-sectional survey in 12 European countries. Eur J Cardiovasc Prev Rehabil 2010;17(5):530-40
  • Hoerger TJ, Bala MV, Bray JW, Treatment patterns and distribution of low-density lipoprotein cholesterol levels in treatment-eligible United States adults. Am J Cardiol 1998;82(1):61-5
  • Schectman G, Hiatt J. Drug therapy for hypercholesterolemia in patients with cardiovascular disease: factors limiting achievement of lipid goals. Am J Med 1996;100(2):197-204
  • Pedersen TR, Faergeman O, Kastelein JJ, High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005;294(19):2437-45
  • de Lemos JA, Blazing MA, Wiviott SD, Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004;292(11):1307-16
  • Hsu I, Spinler SA, Johnson NE. Comparative evaluation of the safety and efficacy of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. Ann Pharmacother 1995;29(7-8):743-59
  • Liberopoulos EN, Florentin M, Mikhailidis DP, Elisaf MS. Compliance with lipid-lowering therapy and its impact on cardiovascular morbidity and mortality. Expert Opin Drug Saf 2008;7(6):717-25
  • Rader DJ, Cohen J, Hobbs HH. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest 2003;111(12):1795-803
  • Gagne C, Gaudet D, Bruckert E. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation 2002;105(21):2469-75
  • Moghadasian MH, Frohlich JJ, Saleem M, Surgical management of dyslipidemia: clinical and experimental evidence. J Invest Surg 2001;14(2):71-8
  • Sachais BS, Katz J, Ross J, Rader DJ. Long-term effects of LDL apheresis in patients with severe hypercholesterolemia. J Clin Apher 2005;20(4):252-5
  • Thompson GR. Recommendations for the use of LDL apheresis. Atherosclerosis 2008;198(2):247-55
  • Lopez-Santamaria M, Migliazza L, Gamez M, Liver transplantation in patients with homozygotic familial hypercholesterolemia previously treated by end-to-side portocaval shunt and ileal bypass. J Pediatr Surg 2000;35(4):630-3
  • Kannel WB. High-density lipoproteins: epidemiologic profile and risks of coronary artery disease. Am J Cardiol 1983;52(4):9B-12B
  • Castelli WP. Epidemiology of triglycerides: a view from Framingham. Am J Cardiol 1992;70(19):3H-9H
  • Lorenzo C, Wagenknecht LE, Hanley AJ, Hemoglobin A1c between 5.7 and 6.4% as a marker for identifying pre-diabetes, insulin sensitivity and secretion, and cardiovascular risk factors: The Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care 2010;33(9):2104-9
  • Cederberg H, Saukkonen T, Laakso M, Postchallenge glucose, HbA1c, and fasting glucose as predictors of type 2 diabetes and cardiovascular disease: a 10-year prospective cohort study. Diabetes Care 2010;33(9):2077-83
  • 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) final report. Circulation 2002;106(25):3143-421
  • Grundy SM, Cleeman JI, Merz CN, Implications of recent clinical trials for the National cholesterol education program adult treatment panel III guidelines. J Am Coll Cardiol 2004;44(3):720-32
  • Lichtenstein AH, Appel LJ, Brands M, Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation 2006;114(1):82-96
  • Ashton EL, Best JD, Ball MJ. Effects of monounsaturated enriched sunflower oil on CHD risk factors including LDL size and copper-induced LDL oxidation. J Am Coll Nutr 2001;20(4):320-6
  • Appel LJ, Sacks FM, Carey VJ, Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. JAMA 2005;294(19):2455-64
  • Daskalopoulou SS, Mikhailidis DP. Reaching goal in hypercholesterolaemia: dual inhibition of cholesterol synthesis and absorption with simvastatin plus ezetimibe. Curr Med Res Opin 2006;22(3):511-28
  • Milionis HJ, Rizos E, Kostapanos M, Treating to target patients with primary hyperlipidaemia: comparison of the effects of ATOrvastatin and ROSuvastatin (the ATOROS study). Curr Med Res Opin 2006;22(6):1123-31
  • Jones PH, Davidson MH, Stein EA, Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol 2003;92(2):152-60
  • Kostapanos MS, Milionis HJ, Filippatos TD, A 12-week, prospective, open-label analysis of the effect of rosuvastatin on triglyceride-rich lipoprotein metabolism in patients with primary dyslipidemia. Clin Ther 2007;29(7):1403-14
  • Crouse JR, III, Raichlen JS, Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA 2007;297(12):1344-53
  • Nissen SE, Nicholls SJ, Sipahi I, Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 2006;295(13):1556-65
  • Barter PJ, Brandrup-Wognsen G, Palmer MK, Nicholls SJ. Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER Database. J Lipid Res 2010;51(6):1546-53
  • Kostapanos MS, Milionis HJ, Elisaf MS. An overview of the extra-lipid effects of rosuvastatin. J Cardiovasc Pharmacol Ther 2008;13(3):157-74
  • Kostapanos MS, Liberopoulos EN, Elisaf MS. Statin pleiotropy against renal injury. J Cardiometab Syndr 2009;4(1):E4-9
  • Kostapanos MS, Liberopoulos EN, Goudevenos JA, Do statins have an antiarrhythmic activity? Cardiovasc Res 2007;75(1):10-20
  • Milionis HJ, Liberopoulos EN, Achimastos A, Statins: another class of antihypertensive agents? J Hum Hypertens 2006;20(5):320-35
  • Kiortsis DN, Filippatos TD, Mikhailidis DP, Statin-associated adverse effects beyond muscle and liver toxicity. Atherosclerosis 2007;195(1):7-16
  • Harper CR, Jacobson TA. The broad spectrum of statin myopathy: from myalgia to rhabdomyolysis. Curr Opin Lipidol 2007;18(4):401-8
  • Altmann SW, Davis HR, Jr, Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 2004;303(5661):1201-4
  • Davis HR, Jr, Zhu LJ, Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J Biol Chem 2004;279(32):33586-92
  • Rivers SM, Kane MP, Busch RS, Colesevelam hydrochloride-ezetimibe combination lipid-lowering therapy in patients with diabetes or metabolic syndrome and a history of statin intolerance. Endocr Pract 2007;13(1):11-16
  • Daskalopoulou SS, Mikhailidis DP. Ezetimibe/simvastatin single tablet versus rosuvastatin in patients with hypercholesterolemia. Curr Med Res Opin 2006;22(10):2037-9
  • Gazi IF, Mikhailidis DP. Non-low-density lipoprotein cholesterol-associated actions of ezetimibe: an overview. Expert Opin Ther Targets 2006;10(6):851-66
  • Kalogirou M, Tsimihodimos V, Gazi I, Effect of ezetimibe monotherapy on the concentration of lipoprotein subfractions in patients with primary dyslipidaemia. Curr Med Res Opin 2007;23(5):1169-76
  • Mikhailidis DP, Wierzbicki AS, Daskalopoulou SS, The use of ezetimibe in achieving low density lipoprotein lowering goals in clinical practice: position statement of a United Kingdom consensus panel. Curr Med Res Opin 2005;21(6):959-69
  • Nakou ES, Filippatos TD, Georgoula M, The effect of orlistat and ezetimibe, alone or in combination, on serum LDL and small dense LDL cholesterol levels in overweight and obese patients with hypercholesterolaemia. Curr Med Res Opin 2008;24(7):1919-29
  • Gazi IF, Daskalopoulou SS, Nair DR, Mikhailidis DP. Effect of ezetimibe in patients who cannot tolerate statins or cannot get to the low density lipoprotein cholesterol target despite taking a statin. Curr Med Res Opin 2007;23(9):2183-92
  • Mikhailidis DP, Sibbring GC, Ballantyne CM, Meta-analysis of the cholesterol-lowering effect of ezetimibe added to ongoing statin therapy. Curr Med Res Opin 2007;23(8):2009-26
  • Sudhop T, Lutjohann D, Kodal A, Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation 2002;106(15):1943-8
  • Florentin M, Liberopoulos EN, Elisaf MS. Ezetimibe-associated adverse effects: what the clinician needs to know. Int J Clin Pract 2008;62(1):88-96
  • Rossebo AB, Pedersen TR, Boman K, Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008;359(13):1343-56
  • Taylor AJ, Villines TC, Stanek EJ, Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009;361(22):2113-22
  • Liberopoulos EN, Rizos CV, Elisaf MS. Should we abandon ezetimibe? CML Cardiology 2008;27:77-89
  • Costanzo P, Perrone-Filardi P, Vassallo E, Does carotid intima-media thickness regression predict reduction of cardiovascular events? A meta-analysis of 41 randomized trials. J Am Coll Cardiol 2010;56(24):2006-20
  • Fleg JL, Mete M, Howard BV, Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial. J Am Coll Cardiol 2008;52(25):2198-205
  • Meaney A, Ceballos G, Asbun J, The VYtorin on Carotid intima-media thickness and overall arterial rigidity (VYCTOR) study. J Clin Pharmacol 2009;49(7):838-47
  • SHARP: Ezetimibe/simvastatin combo cuts atherosclerotic and vascular events in kidney-disease patients. Available from: http://www.theheart.org/article/1155027.do [Accessed 10 December 2010]
  • IMPROVE-IT: Examining outcomes in subjects with acute coronary syndrome: vytorin (Ezetimibe/Simvastatin) vs simvastatin (Study P04103AM3). Available from: http://www.clinicaltrials.gov [Accessed 10 December 2010]
  • Grundy SM, Ahrens EH, Jr, Salen G. Interruption of the enterhepatic circulation of bile acids in man: comparative effects of cholestyramine and ileal exclusion on cholesterol metabolism. J Lab Clin Med 1971;78(1):94-121
  • Einarsson K, Ericsson S, Ewerth S, Bile acid sequestrants: mechanisms of action on bile acid and cholesterol metabolism. Eur J Clin Pharmacol 1991;40(Suppl 1):S53-8
  • Chiang JY. Bile acid regulation of gene expression: roles of nuclear hormone receptors. Endocr Rev 2002;23(4):443-63
  • Shepherd J, Packard CJ, Bicker S, Cholestyramine promotes receptor-mediated low-density-lipoprotein catabolism. N Engl J Med 1980;302(22):1219-22
  • WelChol (colesevelam hydrochloride) Prescribing Information v8. Sankyo Pharma Inc., Parsippany, NJ. Available from: www.welchol.com [Accessed 10 December 2010]
  • Insull W, Jr. Clinical utility of bile acid sequestrants in the treatment of dyslipidemia: a scientific review. South Med J 2006;99(3):257-73
  • Schwartz CC, Halloran LG, Vlahcevic ZR, Preferential utilization of free cholesterol from high-density lipoproteins for biliary cholesterol secretion in man. Science 1978;200(4337):62-4
  • Bravo E, Cantafora A, Argiolas L. Hepatic uptake and metabolism of free cholesterol from different lipoprotein classes. An in vivo study in the rat. Biochim Biophys Acta 1989;1003(3):315-20
  • Robins SJ, Fasulo JM. High density lipoproteins, but not other lipoproteins, provide a vehicle for sterol transport to bile. J Clin Invest 1997;99(3):380-4
  • Schwartz CC, Vlahcevic ZR, Halloran LG, Evidence for the existence of definitive hepatic cholesterol precursor compartments for bile acids and biliary cholesterol in man. Gastroenterology 1975;69(6):1379-82
  • Florentin M, Liberopoulos EN, Mikhailidis DP, Elisaf MS. Colesevelam hydrochloride in clinical practice: a new approach in the treatment of hypercholesterolaemia. Curr Med Res Opin 2008;24(4):995-1009
  • Andrade SE, Walker AM, Gottlieb LK, 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
  • Avorn J, Monette J, Lacour A, Persistence of use of lipid-lowering medications: a cross-national study. JAMA 1998;279(18):1458-62
  • The lipid research clinics coronary primary prevention trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984;251(3):351-64
  • Insull W, Jr, Toth P, Effectiveness of colesevelam hydrochloride in decreasing LDL cholesterol in patients with primary hypercholesterolemia: a 24-week randomized controlled trial. Mayo Clin Proc 2001;76(10):971-82
  • Davidson MH, Dillon MA, Gordon B, Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects. Arch Intern Med 1999;159(16):1893-900
  • Rosenson RS. Colesevelam HCl reduces LDL particle number and increases LDL size in hypercholesterolemia. Atherosclerosis 2006;185(2):327-30
  • Devaraj S, Autret B, Jialal I. Effects of colesevelam hydrochloride (WelChol) on biomarkers of inflammation in patients with mild hypercholesterolemia. Am J Cardiol 2006;98(5):641-3
  • Knapp HH, Schrott H, Ma P, Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia. Am J Med 2001;110(5):352-60
  • Bays HE, Davidson M, Jones MR, Abby SL. Effects of colesevelam hydrochloride on low-density lipoprotein cholesterol and high-sensitivity C-reactive protein when added to statins in patients with hypercholesterolemia. Am J Cardiol 2006;97(8):1198-205
  • Hunninghake D, Insull W, Jr, Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively. Atherosclerosis 2001;158(2):407-16
  • McKenney J, Jones M, Abby S. Safety and efficacy of colesevelam hydrochloride in combination with fenofibrate for the treatment of mixed hyperlipidemia. Curr Med Res Opin 2005;21(9):1403-12
  • Zema MJ. Colesevelam HCl and ezetimibe combination therapy provides effective lipid-lowering in difficult-to-treat patients with hypercholesterolemia. Am J Ther 2005;12(4):306-10
  • Bays H, Rhyne J, Abby S, Lipid-lowering effects of colesevelam HCl in combination with ezetimibe. Curr Med Res Opin 2006;22(11):2191-200
  • Knopp RH, Tsunehara C, Retzlaff BM, Lipoprotein effects of combined ezetimibe and colesevelam hydrochloride versus ezetimibe alone in hypercholesterolemic subjects: a pilot study. Metabolism 2006;55(12):1697-703
  • Kondo K, Kadowaki T. Colestilan monotherapy significantly improves glycaemic control and LDL cholesterol levels in patients with type 2 diabetes: a randomized double-blind placebo-controlled study. Diabetes Obes Metab 2010;12(3):246-51
  • Cheatham WW. Peroxisome proliferator-activated receptor translational research and clinical experience. Am J Clin Nutr 2010;91(1):262S-266S
  • Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med 2002;53:409-35
  • Schreurs M, Kuipers F, van der Leij FR. Regulatory enzymes of mitochondrial beta-oxidation as targets for treatment of the metabolic syndrome. Obes Rev 2010;11(5):380-8
  • Shah A, Rader DJ, Millar JS. The effect of PPAR-alpha agonism on apolipoprotein metabolism in humans. Atherosclerosis 2010;210(1):35-40
  • 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
  • Staels B, Auwerx J. Regulation of apo A-I gene expression by fibrates. Atherosclerosis 1998;137(Suppl):S19-23
  • Chinetti G, Lestavel S, Bocher V, PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med 2001;7(1):53-8
  • Gazi IF, Tsimihodimos V, Tselepis AD, Clinical importance and therapeutic modulation of small dense low-density lipoprotein particles. Expert Opin Biol Ther 2007;7(1):53-72
  • Elisaf M. Effects of fibrates on serum metabolic parameters. Curr Med Res Opin 2002;18(5):269-76
  • Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety considerations with fibrate therapy. Am J Cardiol 2007;99(6A):S3-18
  • Layne RD, Sehbai AS, Stark LJ. Rhabdomyolysis and renal failure associated with gemfibrozil monotherapy. Ann Pharmacother 2004;38(2):232-4
  • Alsheikh-Ali AA, Kuvin JT, Karas RH. Risk of adverse events with fibrates. Am J Cardiol 2004;94(7):935-8
  • Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol 2005;95(1):120-2
  • Alexandridis G, Pappas GA, Elisaf MS. Rhabdomyolysis due to combination therapy with cerivastatin and gemfibrozil. Am J Med 2000;109(3):261-2
  • Davidson MH, McKenney JM, Shear CL, Revkin JH. Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels. J Am Coll Cardiol 2006;48(9):1774-81
  • Florentin M, Liberopoulos EN, Mikhailidis DP, Elisaf MS. Fibrate-associated adverse effects beyond muscle and liver toxicity. Curr Pharm Des 2008;14(6):574-87
  • Chew EY, Ambrosius WT, Davis MD, Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010;363(3):233-44
  • Ansquer JC, Foucher C, Aubonnet P, Le Malicot K. Fibrates and microvascular complications in diabetes-insight from the FIELD study. Curr Pharm Des 2009;15(5):537-52
  • Robins SJ, Rubins HB, Faas FH, Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT). Diabetes Care 2003;26(5):1513-17
  • Rubins HB, Robins SJ, Collins D, Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Arch Intern Med 2002;162(22):2597-604
  • Tenkanen L, Manttari M, Manninen V. Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil. Experience from the Helsinki Heart Study. Circulation 1995;92(7):1779-85
  • Manninen V, Tenkanen L, Koskinen P, Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment. Circulation 1992;85(1):37-45
  • Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. the Bezafibrate Infarction Prevention (BIP) study. Circulation 2000;102(1):21-7
  • Tenenbaum A, Motro M, Fisman EZ, Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med 2005;165(10):1154-60
  • Minihane AM, Khan S, Leigh-Firbank EC, ApoE polymorphism and fish oil supplementation in subjects with an atherogenic lipoprotein phenotype. Arterioscler Thromb Vasc Biol 2000;20(8):1990-7
  • Farmer A, Montori V, Dinneen S, Clar C. Fish oil in people with type 2 diabetes mellitus. Cochrane Database Syst Rev 2001;(3):CD003205
  • Gazi I, Liberopoulos EN, Saougos VG, Elisaf M. Beneficial effects of omega-3 fatty acids: the current evidence. Hellenic J Cardiol 2006;47(4):223-31
  • Rustan AC, Nossen JO, Christiansen EN, Drevon CA. Eicosapentaenoic acid reduces hepatic synthesis and secretion of triacylglycerol by decreasing the activity of acyl-coenzyme A:1,2-diacylglycerol acyltransferase. J Lipid Res 1988;29(11):1417-26
  • Sampath H, Ntambi JM. Polyunsaturated fatty acid regulation of gene expression. Nutr Rev 2004;62(9):333-9
  • Jump DB. Fatty acid regulation of gene transcription. Crit Rev Clin Lab Sci 2004;41(1):41-78
  • Bays HE, Tighe AP, Sadovsky R, Davidson MH. Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert Rev Cardiovasc Ther 2008;6(3):391-409
  • Harris WS. n-3 fatty acids and human lipoprotein metabolism: an update. Lipids 1999;34(Suppl):S257-8
  • Harris WS, Ginsberg HN, Arunakul N, Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk 1997;4(5-6):385-91
  • McKenney JM, Sica D. Role of prescription omega-3 fatty acids in the treatment of hypertriglyceridemia. Pharmacotherapy 2007;27(5):715-28
  • Nambi V, Ballantyne CM. Combination therapy with statins and omega-3 fatty acids. Am J Cardiol 2006;98(4A):34i-38i
  • Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002;106(21):2747-57
  • Hartweg J, Perera R, Montori V, Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus. Cochrane Database Syst Rev 2008;(1):CD003205
  • Hopper L, Ness A, Higgins JP, GISSI-Prevenzione trial. Lancet 1999;354(9189):1557
  • Tavazzi L, Maggioni AP, Marchioli R, Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008;372(9645):1223-30
  • Lavie CJ, Milani RV, Mehra MR, Ventura HO. Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol 2009;54(7):585-94
  • Saravanan P, Davidson NC, Schmidt EB, Calder PC. Cardiovascular effects of marine omega-3 fatty acids. Lancet 376(9740):540-50
  • Guyton JR. Extended-release niacin for modifying the lipoprotein profile. Expert Opin Pharmacother 2004;5(6):1385-98
  • Elam MB, Hunninghake DB, Davis KB, Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: A randomized trial. Arterial Disease Multiple Intervention Trial. JAMA 2000;284(10):1263-70
  • Goldberg A, Alagona P, Jr, Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia. Am J Cardiol 2000;85(9):1100-5
  • White Robinson A, Sloan HL, Arnold G. The antilipidemic effects of plain and extended-release niacin. Prev Cardiol 2000;3(3):131-5
  • Birjmohun RS, Hutten BA, Kastelein JJ, Stroes ES. Increasing HDL cholesterol with extended-release nicotinic acid: from promise to practice. Neth J Med 2004;62(7):229-34
  • Vogt A, Kassner U, Hostalek U, Steinhagen-Thiessen E. Correction of low HDL cholesterol to reduce cardiovascular risk: practical considerations relating to the therapeutic use of prolonged-release nicotinic acid (Niaspan). Int J Clin Pract 2007;61(11):1914-21
  • Ganji SH, Tavintharan S, Zhu D, Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells. J Lipid Res 2004;45(10):1835-45
  • Jin FY, Kamanna VS, Kashyap ML. Niacin accelerates intracellular ApoB degradation by inhibiting triacylglycerol synthesis in human hepatoblastoma (HepG2) cells. Arterioscler Thromb Vasc Biol 1999;19(4):1051-9
  • Carlson LA. Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review. J Intern Med 2005;258(2):94-114
  • Grundy SM, Mok HY, Zech L, Berman M. Influence of nicotinic acid on metabolism of cholesterol and triglycerides in man. J Lipid Res 1981;22(1):24-36
  • Ganji SH, Kamanna VS, Kashyap ML. Niacin and cholesterol: role in cardiovascular disease (review). J Nutr Biochem 2003;14(6):298-305
  • Blum CB, Levy RI, Eisenberg S, High density lipoprotein metabolism in man. J Clin Invest 1977;60(4):795-807
  • Shepherd J, Packard CJ, Patsch JR, Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism. J Clin Invest 1979;63(5):858-67
  • Zhang LH, Kamanna VS, Zhang MC, Kashyap ML. Niacin inhibits surface expression of ATP synthase beta chain in HepG2 cells: implications for raising HDL. J Lipid Res 2008;49(6):1195-201
  • Martinez LO, Jacquet S, Esteve JP, Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis. Nature 2003;421(6918):75-9
  • Soga T, Kamohara M, Takasaki J, Molecular identification of nicotinic acid receptor. Biochem Biophys Res Commun 2003;303(1):364-9
  • Lorenzen A, Stannek C, Lang H, Characterization of a G protein-coupled receptor for nicotinic acid. Mol Pharmacol 2001;59(2):349-57
  • Maciejewski-Lenoir D, Richman JG, Hakak Y, Langerhans cells release prostaglandin D2 in response to nicotinic acid. J Invest Dermatol 2006;126(12):2637-46
  • Carlson LA, Oro L. The effect of nicotinic acid on the plasma free fatty acid; demonstration of a metabolic type of sympathicolysis. Acta Med Scand 1962;172: 641-5
  • Kamanna VS, Ganji SH, Kashyap ML. The mechanism and mitigation of niacin-induced flushing. Int J Clin Pract 2009;63(9):1369-77
  • Alsheikh-Ali AA, Karas RH. The safety of niacin in the US Food and Drug Administration adverse event reporting database. Am J Cardiol 2008;101(8A):9B-13B
  • Kei A, Liberopoulos EN, Elisaf M. What restricts the clinical use of nicotinic acid? Curr Vasc Pharmacol 2010; In press
  • Parhofer KG. Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia. Vasc Health Risk Manag 2009;5:901-8
  • Canner PL, Berge KG, Wenger NK, Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol 1986;8(6):1245-55
  • Carlson LA, Rosenhamer G. Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid. Acta Med Scand 1988;223(5):405-18
  • Brown BG, Zhao XQ, Chait A, Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345(22):1583-92
  • Taylor AJ, Sullenberger LE, Lee HJ, Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation 2004;110(23):3512-17
  • Taylor AJ, Lee HJ, Sullenberger LE. The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin 2006;22(11):2243-50
  • Florentin M, Liberopoulos, Kei A, Pleiotropic effects of nicotinic acid: beyond high density lipoprotein cholesterol elevation. Curr Vasc Pharmacol 2010; In press
  • Niaspan prescribing information. Kos Pharmaceuticals, Inc., Cranbury, NJ; 2005
  • Morrow JD, Parsons WG III, Roberts LJ II. Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid. Prostaglandins 1989;38(2):263-74
  • Goldberg RB, Jacobson TA. Effects of niacin on glucose control in patients with dyslipidemia. Mayo Clin Proc 2008;83(4):470-8
  • Guyton JR, Bays HE. Safety considerations with niacin therapy. Am J Cardiol 2007;99(6A):22C-31C
  • Garg R, Malinow M, Pettinger M, Niacin treatment increases plasma homocyst(e)ine levels. Am Heart J 1999;138(6 Pt 1):1082-7
  • Redberg RF, Benjamin EJ, Bittner V, ACCF/AHA 2009 performance measures for primary prevention of cardiovascular disease in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures (Writing Committee to Develop Performance Measures for Primary Prevention of Cardiovascular Disease) developed in collaboration with the American Academy of Family Physicians; American Association of Cardiovascular and Pulmonary Rehabilitation; and Preventive Cardiovascular Nurses Association: endorsed by the American College of Preventive Medicine, American College of Sports Medicine, and Society for Women's Health Research. J Am Coll Cardiol 2009;54(14):1364-405
  • Cui Y, Blumenthal RS, Flaws JA, Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality. Arch Intern Med 2001;161(11):1413-19
  • van der Steeg WA, Boekholdt SM, Stein EA, Role of the apolipoprotein B-apolipoprotein A-I ratio in cardiovascular risk assessment: a case-control analysis in EPIC-Norfolk. Ann Intern Med 2007;146(9):640-8
  • Sudhop T, von Bergmann K. Cholesterol absorption inhibitors for the treatment of hypercholesterolaemia. Drugs 2002;62(16):2333-47
  • Hussain MM, Shi J, Dreizen P. Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly. J Lipid Res 2003;44(1):22-32
  • Gordon DA, Jamil H. Progress towards understanding the role of microsomal triglyceride transfer protein in apolipoprotein-B lipoprotein assembly. Biochim Biophys Acta 2000;1486(1):72-83
  • Raabe M, Veniant MM, Sullivan MA, Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice. J Clin Invest 1999;103(9):1287-98
  • Tietge UJ, Bakillah A, Maugeais C, Hepatic overexpression of microsomal triglyceride transfer protein (MTP) results in increased in vivo secretion of VLDL triglycerides and apolipoprotein B. J Lipid Res 1999;40(11):2134-9
  • Wetterau JR, Aggerbeck LP, Bouma ME, Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science 1992;258(5084):999-1001
  • Moutzouri E, Elisaf M, Liberopoulos EN. Hypocholesterolemia. Curr Vasc Pharmacol 2010. [Epub ahead of print]
  • Hussain MM, Rava P, Pan X, Microsomal triglyceride transfer protein in plasma and cellular lipid metabolism. Curr Opin Lipidol 2008;19(3):277-84
  • Crooke R, Baker B, Wedel M. Cardiovascular therapeutic applications. In: Crooke ST, ed. Antisense drug technology: principles, strategies and applications. 2nd edition. CRC Press, Boca Raton; 2007:601-39
  • Stein EA. Other therapies for reducing low-density lipoprotein cholesterol: medications in development. Endocrinol Metab Clin North Am 2009;38(1):99-119
  • Raal FJ, Santos RD, Blom DJ, Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet 2010;375(9719):998-1006
  • Gullberg H, Rudling M, Salto C, Requirement for thyroid hormone receptor beta in T3 regulation of cholesterol metabolism in mice. Mol Endocrinol 2002;16(8):1767-77
  • Thompson GR, Soutar AK, Spengel FA, Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. Proc Natl Acad Sci USA 1981;78(4):2591-5
  • Walton KW, Scott PJ, Dykes PW, Davies JW. The significance of alterations in serum lipids in thyroid dysfunction. II. Alterations of the metabolism and turnover of 131-I-low-density lipoproteins in hypothyroidism and thyrotoxicosis. Clin Sci 1965;29(2):217-38
  • Ladenson PW, Kristensen JD, Ridgway EC, Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia. N Engl J Med 2010;362(10):906-16
  • Study of 3,5-Diiodothyropropionic Acid (DITPA) in Hypercholesterolemic Patients. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00311987?term=thyroid+hormone+analogues&rank=2 [Accessed 10 December 2010]
  • Shah PK. High-density lipoprotein mimetics: focus on synthetic high-density lipoprotein. Am J Cardiol 2007;100(11 A):S62-7
  • Dullens SP, Plat J, Mensink RP. Increasing apoA-I production as a target for CHD risk reduction. Nutr Metab Cardiovasc Dis 2007;17(8):616-28
  • Resverlogix Phase 1b/2a Study Meets Primary Endpoint. Available from: http://www.resverlogix.com/upload/latest_news/90/02/2009-08-25_clinical_trial_and_quarterly_update_final.pdf [Accessed 10 December 2010]
  • Franceschini G, Sirtori CR, Capurso A, A-IMilano apoprotein. Decreased high density lipoprotein cholesterol levels with significant lipoprotein modifications and without clinical atherosclerosis in an Italian family. J Clin Invest 1980;66(5):892-900
  • Available from: http://ir.themedicinescompany.com/phoenix [Accessed 10 December 2010]
  • Van Lenten BJ, Wagner AC, Anantharamaiah GM, Apolipoprotein A-I mimetic peptides. Curr Atheroscler Rep 2009;11(1):52-7
  • Navab M, Shechter I, Anantharamaiah GM, Structure and function of HDL mimetics. Arterioscler Thromb Vasc Biol 2010;30(2):164-8
  • Tall AR. Plasma cholesteryl ester transfer protein. J Lipid Res 1993;34(8):1255-74
  • Chandler CE, Wilder DE, Pettini JL, CP-346086: an MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans. J Lipid Res 2003;44(10):1887-901
  • Wierzbicki AS, Hardman T, Prince WT. Future challenges for microsomal transport protein inhibitors. Curr Vasc Pharmacol 2009;7(3):277-86
  • Cuchel M, Bloedon LT, Szapary PO, Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med 2007;356(2):148-56
  • Samaha FF, McKenney J, Bloedon LT, Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia. Nat Clin Pract Cardiovasc Med 2008;5(8):497-505
  • Preliminary Phase III data also shows signs of efficacy, safety and tolerability in most severe patient population. Available from: http://www.aegerion.com/newsroom/news_2008-11-06.htm. [Accessed 10 December 2010]
  • Aegerion Pharmaceuticals Announces Final Lomitapide (AEGR-733) Phase II data. Available from: http://www.aegerion.com/newsroom/news_2009-06-16.htm [Accessed 10 December 2010]
  • Aegerion Pharmaceuticals Announces Additional Lomitapide (AEGR-733) Phase III data demonstrates significant lowering of LDL cholesterol with promising safety profile. Available from: http://www.aegerion.com/newsroom/news_2009-11-16.htm [Accessed 10 December 2010]
  • Liao W, Chan L. Apolipoprotein B, a paradigm for proteins regulated by intracellular degradation, does not undergo intracellular degradation in CaCo2 cells. J Biol Chem 2000;275(6):3950-6
  • Farnier M, Stein E, Megnien S, Efficacy and safety of implitapide, a microsomal triglyceride protein inhibitor in patients with primary hypercholesterolemia [abstract]. International Symposium on Drugs Affecting Liver Metabolism 2001
  • Aggarwal D, West KL, Zern TL, JTT-130, a microsomal triglyceride transfer protein (MTP) inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic triglycerides in guinea pigs. BMC Cardiovasc Disord 2005;5:30
  • Prince WJ, Tong W, Frekany J, SLX-4090- repeat dose treatment with a novel enterocyte specific MTP inhibitor reduces post-prandial triglyceride response and lowers LDL-C in healthy volunteers. J Clin Lipidol 2007;1:471, abstract 334
  • Stevenson M. Therapeutic potential of RNA interference. N Engl J Med 2004;351(17):1772-7
  • Zimmermann TS, Lee AC, Akinc A, RNAi-mediated gene silencing in non-human primates. Nature 2006;441(7089):111-14
  • Soutschek J, Akinc A, Bramlage B, Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 2004;432(7014):173-8
  • Crooke RM, Graham MJ, Lemonidis KM, An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis. J Lipid Res 2005;46(5):872-84
  • Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004;114(2):147-52
  • Hardie DG. Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology 2003;144(12):5179-83
  • Akdim F, Visser ME, Tribble DL, Effect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia. Am J Cardiol 2010;105(10):1413-19
  • Akdim F, Stroes ES, Sijbrands EJ, Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy. J Am Coll Cardiol 2010;55(15):1611-18
  • Open Label Extension of ISIS 301012 to Treat Familial Hypercholesterolemia. Available from: http://www.genzymeclinicalresearch.com/clinicaltrials/trialdetailresults.asp?nct=NCT00477594 [Accessed 10 December 2010]
  • Dose-Escalating Safety Study of ISIS 301012 in homozygous familial hypercholesterolemia subjects on lipid lowering therapy. Available from: http://www.genzymeclinicalresearch.com/clinicaltrials/trialdetailresults.asp?nct=NCT00280995 [Accessed 10 December 2010]
  • Safety and efficacy of Mipomersen in patients with severe hypercholesterolemia on a maximally tolerated lipid-lowering regimen and who are not on apheresis. Available from: http://www.genzymeclinicalresearch.com/clinicaltrials/trialdetailresults.asp?nct=NCT00794664 [Accessed 10 December 2010]
  • Genzyme and Isis Report Results of Two Phase 3 Trials of Mipomersen; Studies meet primary endpoints with 36 and 37 percent LDL-C reductions in severe hypercholesterolemia and high-risk patients companies complete phase 3 studies planned to support initial filings Available from: http://www.genzymecli nicalresearch.com/clinicaltrials/trialsearchresults.asp?show=all&product=mipomersen [Accessed 10 December 2010]
  • Yu RZ, Geary RS, Flaim JD, Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2′-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe. Clin Pharmacokinet 2009;48(1):39-50
  • Safety and efficacy study of 301012 administration in high risk statin intolerant subjects. Available from: http://www.genzymeclinicalresearch.com/clinicaltrials/trialdetailresults.asp?nct=NCT00707746 [Accessed 10 December 2010]
  • Available from: http://www.genzymeclinicalresearch.com/clinicaltrials/trialsearchresults.asp?show=active&product=mipomersen [Accessed 10 December 2010]
  • Berkenstam A, Kristensen J, Mellstrom K, The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans. Proc Natl Acad Sci USA 2008;105(2):663-7
  • Berry MJ, Kates AL, Larsen PR. Thyroid hormone regulates type I deiodinase messenger RNA in rat liver. Mol Endocrinol 1990;4(5):743-8
  • Resverlogix Corp.-Press releases. Available from: http://www.resverlogix.com/search.html?search=ASSERT [Accessed 10 December 2010]
  • Assert trial. Available from: http://www.theheart.org/article/1153279.do [Accessed 10 December 2010]
  • Tardif JC, Gregoire J, L'Allier PL, Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 2007;297(15):1675-82
  • Wang L, Sharifi BG, Pan T, Bone marrow transplantation shows superior atheroprotective effects of gene therapy with apolipoprotein A-I Milano compared with wild-type apolipoprotein A-I in hyperlipidemic mice. J Am Coll Cardiol 2006;48(7):1459-68
  • Nissen SE, Tsunoda T, Tuzcu EM, Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 2003;290(17):2292-300
  • Kastelein JJ, van Leuven SI, Burgess L, Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med 2007;356(16):1620-30
  • Nicholls SJ, Tuzcu EM, Brennan DM, Cholesteryl ester transfer protein inhibition, high-density lipoprotein raising, and progression of coronary atherosclerosis: insights from ILLUSTRATE (Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation). Circulation 2008;118(24):2506-14
  • Vergeer M, Bots ML, van Leuven SI, Cholesteryl ester transfer protein inhibitor torcetrapib and off-target toxicity: a pooled analysis of the rating atherosclerotic disease change by imaging with a new CETP inhibitor (RADIANCE) trials. Circulation 2008;118(24):2515-22
  • McKenney JM, Davidson MH, Shear CL, Revkin JH. Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels on a background of atorvastatin. J Am Coll Cardiol 2006;48(9):1782-90
  • Hu X, Dietz JD, Xia C, Torcetrapib induces aldosterone and cortisol production by an intracellular calcium-mediated mechanism independently of cholesteryl ester transfer protein inhibition. Endocrinology 2009;150(5):2211-19
  • Forrest MJ, Bloomfield D, Briscoe RJ, Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. Br J Pharmacol 2008;154(7):1465-73
  • Gurfinkel R, Joy TR. Anacetrapib: hope for CETP inhibitors? Cardiovasc Ther 2010. [Epub ahead of print]
  • Krishna R, Bergman AJ, Jin B, Multiple-dose pharmacodynamics and pharmacokinetics of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Clin Pharmacol Ther 2008;84(6):679-83
  • Krishna R, Anderson MS, Bergman AJ, Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled phase I studies. Lancet 2007;370(9603):1907-14
  • Bloomfield D, Carlson GL, Sapre A, Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients. Am Heart J 2009;157(2):, 352-60 e2
  • Krishna R, Garg A, Jin B, Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Br J Clin Pharmacol 2009;67(5):520-6
  • Cannon CP, Shah S, Dansky HM, Safety of Anacetrapib in Patients with or at High Risk for Coronary Heart Disease. N Engl J Med 2010. [Epub ahead of print]
  • O'Neill E, Sparrow CP, Chen Y, Identification and characterization of MK-0859, a novel cholesteryl ester transfer protein inhibitor. J Clin Lipidol 2007;1:367
  • Shinkai H, Maeda K, Yamasaki T, bis(2-(Acylamino)phenyl) disulfides, 2-(acylamino)benzenethiols, and S-(2-(acylamino)phenyl) alkanethioates as novel inhibitors of cholesteryl ester transfer protein. J Med Chem 2000;43(19):3566-72
  • de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation 2002;105(18):2159-65
  • Kuivenhoven JA, de Grooth GJ, Kawamura H, Effectiveness of inhibition of cholesteryl ester transfer protein by JTT-705 in combination with pravastatin in type II dyslipidemia. Am J Cardiol 2005;95(9):1085-8
  • Hermann F, Enseleit F, Spieker LE, Cholesterylestertransfer protein inhibition and endothelial function in type II hyperlipidemia. Thromb Res 2009;123(3):460-5
  • Schwartz GG, Olsson AG, Ballantyne CM, Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome. Am Heart J 2009;158(6):, 896-901 e3
  • Tall AR, Yvan-Charvet L, Wang N. The failure of torcetrapib: was it the molecule or the mechanism? Arterioscler Thromb Vasc Biol 2007;27(2):257-60
  • Florentin M, Liberopoulos EN, Wierzbicki AS, Mikhailidis DP. Multiple actions of high-density lipoprotein. Curr Opin Cardiol 2008;23(4):370-8
  • Miller NE. Associations of high-density lipoprotein subclasses and apolipoproteins with ischemic heart disease and coronary atherosclerosis. Am Heart J 1987;113(2 Pt 2):589-97
  • Barter P, Kastelein J, Nunn A, Hobbs R. High density lipoproteins (HDLs) and atherosclerosis; the unanswered questions. Atheroscler Suppl 2003;168(2):195-211
  • Kontush A, Chapman MJ. Antiatherogenic small, dense HDL-guardian angel of the arterial wall? Nat Clin Pract Cardiovasc Med 2006;3(3):144-53
  • Kontush A, Guerin M, Chapman MJ. Spotlight on HDL-raising therapies: insights from the torcetrapib trials. Nat Clin Pract Cardiovasc Med 2008;5(6):329-36
  • Hofmann AF. The continuing importance of bile acids in liver and intestinal disease. Arch Intern Med 1999;159(22):2647-58
  • West KL, Zern TL, Butteiger DN, SC-435, an ileal apical sodium co-dependent bile acid transporter (ASBT) inhibitor lowers plasma cholesterol and reduces atherosclerosis in guinea pigs. Atherosclerosis 2003;171(2):201-10
  • Bhat BG, Rapp SR, Beaudry JA, Inhibition of ileal bile acid transport and reduced atherosclerosis in apoE-/- mice by SC-435. J Lipid Res 2003;44(9):1614-21
  • Li H, Xu G, Shang Q, Inhibition of ileal bile acid transport lowers plasma cholesterol levels by inactivating hepatic farnesoid X receptor and stimulating cholesterol 7 alpha-hydroxylase. Metabolism 2004;53(7):927-32
  • Nicolosi RJ, Wilson TA, Krause BR. The ACAT inhibitor, CI-1011 is effective in the prevention and regression of aortic fatty streak area in hamsters. Atherosclerosis 1998;137(1):77-85
  • Asami Y, Yamagishi I, Akiyoshi K, Inhibitory effect of TS-962 on the formation of early atherosclerotic lesions in high fat-fed hyperlipidemic hamsters. Atherosclerosis 1999;146(2):237-42
  • Tardif JC, Gregoire J, L'Allier PL, Effects of the acyl coenzyme A:cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions. Circulation 2004;110(21):3372-7
  • Nissen SE, Tuzcu EM, Brewer HB, Effect of ACAT inhibition on the progression of coronary atherosclerosis. N Engl J Med 2006;354(12):1253-63
  • Seiki S, Frishman WH. Pharmacologic inhibition of squalene synthase and other downstream enzymes of the cholesterol synthesis pathway: a new therapeutic approach to treatment of hypercholesterolemia. Cardiol Rev 2009;17(2):70-6
  • Tavridou A, Kaklamanis L, Megaritis G, Pharmacological characterization in vitro of EP2306 and EP2302, potent inhibitors of squalene synthase and lipid biosynthesis. Eur J Pharmacol 2006;535(1-3):34-42
  • Ugawa T, Kakuta H, Moritani H, YM-53601, a novel squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in several animal species. Br J Pharmacol 2000;131(1):63-70
  • Hiyoshi H, Yanagimachi M, Ito M, Effect of ER-27856, a novel squalene synthase inhibitor, on plasma cholesterol in rhesus monkeys: comparison with 3-hydroxy-3-methylglutaryl-coa reductase inhibitors. J Lipid Res 2000;41(7):1136-44
  • Davidson MH. Squalene synthase inhibition: a novel target for the management of dyslipidemia. Curr Atheroscler Rep 2007;9(1):78-80
  • Takeda Pharmaceutical Company Limited press release - discontinuation of development of TAK-475, a compound for treatment of hypercholesterolemia. Available from: http://www.takeda.com/press/article_29153.html [Accessed 10 December 2010]
  • Connolly TJ, Carruthers A, Melchior DL. Effect of bilayer cholesterol content on reconstituted human erythrocyte sugar transporter activity. J Biol Chem 1985;260(5):2617-20
  • Porter JA, Young KE, Beachy PA. Cholesterol modification of hedgehog signaling proteins in animal development. Science 1996;274(5285):255-9
  • Clayton PT. Disorders of cholesterol biosynthesis. Arch Dis Child 1998;78(2):185-9
  • Lagace TA, Curtis DE, Garuti R, Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest 2006;116(11):2995-3005
  • Frank-Kamenetsky M, Grefhorst A, Anderson NN, Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci USA 2008;105(33):11915-20
  • Graham MJ, Lemonidis KM, Whipple CP, Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. J Lipid Res 2007;48(4):763-7
  • Duff CJ, Scott MJ, Kirby IT, Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J 2009;419(3):577-84
  • Marian AJ. PCSK9 as a therapeutic target in atherosclerosis. Curr Atheroscler Rep 2010;12(3):151-4
  • Cohen JC, Boerwinkle E, Mosley TH, Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006;354(12):1264-72
  • Abifadel M, Rabes JP, Devillers M, Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum Mutat 2009;30(4):520-9
  • Available from: http://www.clinicaltrials.gov/ct2/results?term=pcsk9 [Accessed 10 December 2010]

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.