New lipid-lowering drugs: An update

International Journal of Clinical Practice

Volumn 66, Issue 3, 2012, Pages 270-280

  Wierzbicki, A S ^a   Hardman, T C ^b   Viljoen, A ^c  

^a ST THOMAS HOSPITAL   (United Kingdom)

^b Niche Science and Technology   (United Kingdom)

^c LISTER HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALIPOGENE TIPARVOVEC; ANTILIPEMIC AGENT; ANTISENSE OLIGONUCLEOTIDE; ATORVASTATIN; AVASIMIBE; BILE ACID SEQUESTRANT; CHOLESTEROL ACYLTRANSFERASE INHIBITOR; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; COLESEVELAM; EPROTIROME; FIBRIC ACID DERIVATIVE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LAPAQUISTAT; LAROPIPRANT; LOMITAPIDE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MICROSOMAL TRANSFER PROTEIN INHIBITOR; NCX 6560; NICOTINIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PHOSPHOLIPASE INHIBITOR; PITIVASTATIN; PPD 10558; ROSUVASTATIN; SOBETIROME; SQUALENE SYNTHASE INHIBITOR; THYROMIMETIC AGENT; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; DRUG WITHDRAWAL; DYSLIPIDEMIA; FAMILIAL HYPERCHOLESTEROLEMIA; FLUSHING; GENE THERAPY; HUMAN; HYPERLIPIDEMIA; HYPERLIPOPROTEINEMIA TYPE 1; HYPERTRIGLYCERIDEMIA; INFLAMMATION; LIVER DYSFUNCTION; LIVER TOXICITY; MYALGIA; MYOSITIS; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIDE EFFECT;

ACETYL-COA C-ACETYLTRANSFERASE; CARRIER PROTEINS; CHOLESTEROL ESTER TRANSFER PROTEINS; CHOLESTEROL, HDL; DRUG COMBINATIONS; FARNESYL-DIPHOSPHATE FARNESYLTRANSFERASE; GENE THERAPY; HUMANS; HYPERLIPIDEMIAS; HYPOLIPIDEMIC AGENTS; LIPOTROPIC AGENTS; OLIGONUCLEOTIDES, ANTISENSE; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; PROPROTEIN CONVERTASES; TRIGLYCERIDES;

EID: 84857351347     PISSN: 13685031     EISSN: 17421241     Source Type: Journal    
DOI: 10.1111/j.1742-1241.2011.02867.x     Document Type: Review

References (133)

1. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP). JAMA 2001; 285 (19): 2486-97.
2. British Cardiac Society, British Hypertension Society, Diabetes UK, HEART UK, Primary Care Cardiovascular Society, The Stroke Association. JBS 2: the Joint British Societies' guidelines for prevention of cardiovascular disease in clinical practice. Heart 2005; 91 (Suppl. V): v1-52.
3. Graham I, Atar D, Borch-Johnsen K, et al., European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Atherosclerosis 2007; 194 (1): 1-45. (Pubitemid 47470068)
4. Teslovich TM, Musunuru K, Smith AV, et al., Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010; 466 (7307): 707-13.
5. Sacks FM. The role of high-density lipoprotein (HDL) cholesterol in the prevention and treatment of coronary heart disease: expert group recommendations. Am J Cardiol 2002; 90 (2): 139-43. (Pubitemid 34775122)
6. Danesh J, Erqou S, Walker M, et al., The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases. Eur J Epidemiol 2007; 22 (12): 839-69.
7. Sarwar N, Danesh J, Eiriksdottir G, et al., Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation 2007; 115 (4): 450-8. (Pubitemid 46184196)
8. Chapman MJ, Ginsberg HN, Amarenco P, et al., Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011; 32 (11): 1345-61.
9. Fruchart JC, Sacks F, Hermans MP, et al., The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia. Am J Cardiol 2008; 102 (10 Suppl.): 1K-34K.
10. Wierzbicki AS. Lipid-altering agents: the future. Int J Clin Pract 2004; 58 (11): 1063-72. (Pubitemid 39642422)
11. Wierzbicki AS, Poston R, Ferro A. The lipid and non-lipid effects of statins. Pharmacol Ther 2003; 99 (1): 95-112. (Pubitemid 36694752)
12. Nicholls SJ, Ballantyne CM, Barter PJ, et al., Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011; 365 (22): 2078-87.
13. Maruyama T, Takada M, Nishibori Y, et al., Comparison of preventive effect on cardiovascular events with different statins-The CIRCLE study. Circ J 2011; 75 (8): 1951-9.
14. Djian JP, Maucci R, Guilmin L, Ferreira T, Pfister P. NCX 6560, a novel nitric oxide donating atorvastatin with a promising safety and efficacy profile: A randomised, double blind placebo and active control study. Circulation 2010; 122 (21 Suppl.): A14267 [abstract].
15. Furiex Pharamceuticals Inc. Study of the safety and tolerability associated with PPD10558 versus atorvastatin in patients previously intolerant to statins due to statin-associated myalgia (SAM). ClinicalTrials Gov. 23 September 2011. (accessed 10 October 2011).
16. Jun M, Foote C, Lv J, et al., Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 2010; 375 (9729): 1875-84.
17. Ginsberg HN, Elam MB, Lovato LC, et al., Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010; 362 (17): 1563-74.
18. Wierzbicki AS. Fibrates: no ACCORD on their use in the treatment of dyslipidaemia. Curr Opin Lipidol 2010; 21 (4): 352-8.
19. Keech AC, Mitchell P, Summanen PA, et al., Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 2007; 370 (9600): 1687-97. (Pubitemid 350100775)
20. Manghat P, Wierzbicki AS. Colesevelam-a specifically engineered bile acid sequestrant. Fut Lipidol 2008; 3 (3): 237-55. (Pubitemid 352015399)
21. Wierzbicki AS. Niacin: the only vitamin that reduces cardiovascular events. Int J Clin Pract 2011; 65 (4): 379-85.
22. The Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease. JAMA 1975; 231 (4): 360-81.
23. AIM-HIGH investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011, in press.
24. HPS2-THRIVE investigators. A randomized trial of the long-term clinical effects of raising HDL cholesterol with extended release niacin/laropiprant. Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE). ClinicalTrials gov. 2 February 2009. NCT00461630. (accessed 10 October 2011).
25. Arisaph Pharmaceuticals. FDA Accepts Investigational New Drug Application for ARI-3037MO; First in Man Clinical Trial Set to Begin During First Quarter of 2011. Arisaph Pharmaceuticals 2011 March 18 [cited 2011 Oct 10]; Available from: URL: (accessed 10 October 2011).
26. 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.
27. Stein EA, Bays H, O'Brien D, Pedicano J, Piper E, Spezzi A. Lapaquistat acetate: development of a squalene synthase inhibitor for the treatment of hypercholesterolemia. Circulation 2011; 123 (18): 1974-85.
28. Wierzbicki AS, Hardman T, Prince WT. Future challenges for microsomal transport protein inhibitors. Curr Vasc Pharmacol 2009; 7 (3): 277-86.
29. Cuchel M, Bloedon LT, Szapary PO, et al., Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med 2007; 356 (2): 148-56. (Pubitemid 46089675)
30. Samaha FF, McKenney J, Bloedon LT, Sasiela WJ, Rader DJ. 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.
31. Taghibiglou C, Van Iderstine SC, Kulinski A, Rudy D, Adeli K. Intracellular mechanisms mediating the inhibition of apoB-containing lipoprotein synthesis and secretion in HepG2 cells by avasimibe (CI-1011), a novel acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor. Biochem Pharmacol 2002; 63 (3): 349-60. (Pubitemid 34169715)
32. Tardif JC, Gregoire J, L'Allier PL, et al., Effects of the acyl coenzyme A: cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions. Circulation 2004; 110 (21): 3372-7. (Pubitemid 39557502)
33. Nissen SE, Tuzcu EM, Brewer HB, et al., Effect of ACAT inhibition on the progression of coronary atherosclerosis. N Engl J Med 2006; 354 (12): 1253-63.
34. Meuwese MC, de GE, Duivenvoorden R, et al., ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial. JAMA 2009; 301 (11): 1131-9.
35. Yoshinaka Y, Shibata H, Kobayashi H, et al., A selective ACAT-1 inhibitor, K-604, stimulates collagen production in cultured smooth muscle cells and alters plaque phenotype in apolipoprotein E-knockout mice. Atherosclerosis 2010; 213 (1): 85-91.
36. Canner PL, Berge KG, Wenger NK, et al., Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol 1986; 8 (6): 1245-55. (Pubitemid 17208898)
37. Morkin E, Ladenson P, Goldman S, Adamson C. Thyroid hormone analogs for treatment of hypercholesterolemia and heart failure: past, present and future prospects. J Mol Cell Cardiol 2004; 37 (6): 1137-46. (Pubitemid 39585161)
38. Ladenson PW, Kristensen JD, Ridgway EC, et al., Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia. N Engl J Med 2010; 362 (10): 906-16.
39. Lopez D, Abisambra Socarras JF, Bedi M, Ness GC. Activation of the hepatic LDL receptor promoter by thyroid hormone. Biochim Biophys Acta 2007; 1771 (9): 1216-25. (Pubitemid 47404963)
40. Parhofer KG. Lipoprotein(a): medical treatment options for an elusive molecule. Curr Pharm Des 2011; 17 (9): 871-6.
41. Oberbauer R. Not nonsense but antisense-applications of antisense oligonucleotides in different fields of medicine. Wien Klin Wochenschr 1997; 109 (2): 40-6. (Pubitemid 27081119)
42. Straarup EM, Fisker N, Hedtjarn M, et al., Short locked nucleic acid antisense oligonucleotides potently reduce apolipoprotein B mRNA and serum cholesterol in mice and non-human primates. Nucleic Acids Res 2010; 38 (20): 7100-11.
43. Biessen EA, Vietsch H, Rump ET, et al., Targeted delivery of oligodeoxynucleotides to parenchymal liver cells in vivo. Biochem J 1999; 340 (Pt 3): 783-92. (Pubitemid 29312878)
44. Kastelein JJ, Wedel MK, Baker BF, et al., Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation 2006; 114 (16): 1729-35. (Pubitemid 44607121)
45. Akdim F, Tribble DL, Flaim JD, et al., Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia. Eur Heart J 2011, in press.
46. Raal FJ, Santos RD, Blom DJ, et al., 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.
47. Visser ME, Akdim F, Tribble DL, et al., Effect of apolipoprotein-B synthesis inhibition on liver triglyceride content in patients with familial hypercholesterolemia. J Lipid Res 2010; 51 (5): 1057-62.
48. Ason B, Castro-Perez J, Tep S, et al., ApoB siRNA-induced liver steatosis is resistant to clearance by the loss of fatty acid transport protein 5 (Fatp5). Lipids 2011; 46 (11): 991-1003.
49. Tarugi P, Averna M. Hypobetalipoproteinemia: genetics, biochemistry, and clinical spectrum. Adv Clin Chem 2011; 54: 81-107.
50. Cohn JS, Tremblay M, Batal R, et al., Increased apoC-III production is a characteristic feature of patients with hypertriglyceridemia. Atherosclerosis 2004; 177 (1): 137-45. (Pubitemid 39361148)
51. Holmberg R, Refai E, Hoog A, et al., Lowering apolipoprotein CIII delays onset of type 1 diabetes. Proc Natl Acad Sci USA 2011; 108 (26): 10685-9.
52. Tibolla G, Norata GD, Artali R, Meneghetti F, Catapano AL. Proprotein convertase subtilisin/kexin type 9 (PCSK9): from structure-function relation to therapeutic inhibition. Nutr Metab Cardiovasc Dis 2011; 21 (11): 835-43.
53. Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006; 354 (12): 1264-72.
54. Cariou B, Ouguerram K, Zair Y, et al., PCSK9 dominant negative mutant results in increased LDL catabolic rate and familial hypobetalipoproteinemia. Arterioscler Thromb Vasc Biol 2009; 29 (12): 2191-7.
55. Baass A, Dubuc G, Tremblay M, et al., Plasma PCSK9 is associated with age, sex, and multiple metabolic markers in a population-based sample of children and adolescents. Clin Chem 2009; 55 (9): 1637-45.
56. Lambert G, Ancellin N, Charlton F, et al., Plasma PCSK9 concentrations correlate with LDL and total cholesterol in diabetic patients and are decreased by fenofibrate treatment. Clin Chem 2008; 54 (6): 1038-45. (Pubitemid 351793411)
57. Li H, Dong B, Park SW, Lee HS, Chen W, Liu J. Hepatocyte nuclear factor 1alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine. J Biol Chem 2009; 284 (42): 28885-95.
58. Hooper AJ, Marais AD, Tanyanyiwa DM, Burnett JR. The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis 2007; 193 (2): 445-8. (Pubitemid 47058112)
59. Mbikay M, Sirois F, Mayne J, et al., PCSK9-deficient mice exhibit impaired glucose tolerance and pancreatic islet abnormalities. FEBS Lett 2010; 584 (4): 701-6.
60. Duff CJ, Scott MJ, Kirby IT, Hutchinson SE, Martin SL, Hooper NM. Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J 2009; 419 (3): 577-84.
61. Swergold G, Biedermann S, Renard R, Nadler D, Wu R, Mellis S. Safety, lipid, and lipoprotein effects of REGN727/SAR236553, a fully-human proprotein convertase subtilisin kexin 9 (PCSK9) monoclonal antibody administered intravenously to healthy volunteers. Circulation 2010; 122 (21 Suppl.): A2325 [abstract].
62. Amgen. TIMI-57-a double-blind, randomized, placebo-controlled, multicenter, dose-ranging study to evaluate tolerability and efficacy of AMG 145 on low-density lipoprotein cholesterol (LDL-C) in combination with HMG-CoA reductase inhibitors in hypercholesterolemic subjects. ClinicalTrials.Gov 2011 September 29 [cited 2011 Oct 10]; Available from: URL: (accessed 10 October 2011).
63. Frank-Kamenetsky M, Grefhorst A, Anderson NN, et al., 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.
64. Swergold G, Smith W, Mellis S, et al., Inhibition of proprotein convertase subtilisin/kexin type 9 with a monoclonal antibody REGN727/SAR236553, effectively reduces low-density-lipoprotein cholesterol, as mono or add-on therapy in heterozygous familial and non familial hypercholesterolemia. Circulation 2011; 124 (21 Suppl.): A16265 [abstract].
65. Dias C, Shaywitz A, Smith B, et al., A Phase 1, randomized, double-blind, placebo-controlled, ascending single dose study to evaluate the safety, tolerability and pharmacodynamics of AMG145. Circulation 2011; 124 (21 Suppl.): A10701 [abstract].
66. Gylling H, Miettinen TA. Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism 1999; 48 (5): 575-80. (Pubitemid 29230516)
67. Buchwald H, Varco RL, Matts JP, et al., Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med 1990; 323 (14): 946-55. (Pubitemid 20332334)
68. Wierzbicki AS. The ezetimibe Jonah: the trials and tribulations of an unlucky drug. Int J Clin Pract 2011; 65 (12): 1207-8.
69. Wierzbicki AS. A fishy business: omega-3 fatty acids and cardiovascular disease. Int J Clin Pract 2008; 62 (8): 1142-6. (Pubitemid 351977613)
70. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999; 354 (9177): 447-55.
71. Yokoyama M, Origasa H, Matsuzaki M, et al., Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007; 369 (9567): 1090-8. (Pubitemid 46483662)
72. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). Am J Cardiol 2011; 108 (5): 682-90.
73. Oh da Y, Talukdar S, Bae EJ, et al., GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010; 142 (5): 687-98.
74. Chen HC, Farese RV Jr. Inhibition of triglyceride synthesis as a treatment strategy for obesity: lessons from DGAT1-deficient mice. Arterioscler Thromb Vasc Biol 2005; 25 (3): 482-6. (Pubitemid 40330925)
75. Le Bloc'h J, Leray V, Chetiveaux M, et al., Nicotinic acid decreases apolipoprotein B100-containing lipoprotein levels by reducing hepatic very low density lipoprotein secretion through a possible diacylglycerol acyltransferase 2 inhibition in obese dogs. J Pharmacol Exp Ther 2010; 334 (2): 583-9.
76. Novartis Pharmaceuticals. LCQ-908. A 12 week study in patients with type 2 diabetes mellitus (T2DM). ClinicalTrials Gov. 1 October 2011. (accessed October 2011).
77. Rader DJ. Molecular regulation of HDL metabolism and function: implications for novel therapies. J Clin Invest 2006; 116 (12): 3090-100. (Pubitemid 44878620)
78. Di Angelantonio E, Sarwar N, Perry P, et al., Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009; 302 (18): 1993-2000.
79. Birjmohun RS, Hutten BA, Kastelein JJ, Stroes ES. Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials. J Am Coll Cardiol 2005; 45 (2): 185-97. (Pubitemid 40094724)
80. Tall AR. CETP inhibitors to increase HDL cholesterol levels. N Engl J Med 2007; 356 (13): 1364-6. (Pubitemid 46513305)
81. Bisgaier CL, Siebenkas MV, Brown ML, et al., Familial cholesteryl ester transfer protein deficiency is associated with triglyceride-rich low density lipoproteins containing cholesteryl esters of probable intracellular origin. J Lipid Res 1991; 32 (1): 21-33.
82. Barter PJ, Caulfield M, Eriksson M, et al., Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007; 357 (21): 2109-22. (Pubitemid 350146106)
83. Brousseau ME, Diffenderfer MR, Millar JS, et al., Effects of cholesteryl ester transfer protein inhibition on high-density lipoprotein subspecies, apolipoprotein A-I metabolism, and fecal sterol excretion. Arterioscler Thromb Vasc Biol 2005; 25 (5): 1057-64. (Pubitemid 40627855)
84. Vergeer M, Bots ML, van Leuven SI, et al., 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.
85. Barter PJ, Rye KA, Tardif JC, et al., Effect of torcetrapib on glucose, insulin, and hemoglobin A1c in subjects in the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial. Circulation 2011; 124 (5): 555-62.
86. Simic B, Hermann M, Shaw SG, et al., Torcetrapib impairs endothelial function in hypertension. Eur Heart J 2011, in press.
87. Stein EA, Roth EM, Rhyne JM, Burgess T, Kallend D, Robinson JG. Safety and tolerability of dalcetrapib (RO4607381/JTT-705): results from a 48-week trial. Eur Heart J 2010; 31 (4): 480-8.
88. Hermann F, Enseleit F, Spieker LE, et al., Cholesterylestertransfer protein inhibition and endothelial function in type II hyperlipidemia. Thromb Res 2009; 123 (3): 460-5.
89. Luscher TF, Taddei S, Kaski JC, et al., Efficacy and safety of dalcetrapib in patients with or at risk of coronary heart disease-the dal-VESSEL trial. European Society of Cardiology Congress 2011. 2011 August 28 [cited 2011 Oct 10]; Available from: URL: (accessed 10 October 2011)
90. Fayad ZA, Mani V, Woodward M, et al., Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial. Lancet 2011; 378 (9802): 1547-59.
91. Schwartz GG, Olsson AG, Ballantyne CM, et al., 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.
92. Cannon CP, Shah S, Dansky HM, et al., Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med 2010; 363 (25): 2406-15.
93. CTSU University of Oxford. REVEAL: Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification. ClinicalTrials Gov. 1 December 2010. (accessed February 2011).
94. Nicholls SJ, Brewer HB, Kastelein JJ, et al., Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA 2011; 306 (19): 2099-109.
95. Dasari MR, Bapat A, Vittal S, et al., Safety, tolerability, pharmacokinetic and pharmacodynamic profile of multiple-doses of DRL-17822, a potent cholesteryl ester transfer protein inhibitor in healthy male subjects. Circulation 2010; 122 (21 Suppl.): A13981 [abstract].
96. Stumvoll M, Haring HU. Glitazones: clinical effects and molecular mechanisms. Ann Med 2002; 34 (3): 217-24. (Pubitemid 34804195)
97. Singh S, Loke YK, Furberg CD. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA 2007; 298 (10): 1189-95. (Pubitemid 47403105)
98. Dormandy JA, Charbonnel B, Eckland DJ, et al., Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005; 366 (9493): 1279-89. (Pubitemid 41416583)
99. Kendall DM, Rubin CJ, Mohideen P, et al., Improvement of glycemic control, triglycerides, and HDL cholesterol levels with muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor activator, in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a double-blind, randomized, pioglitazone-comparative study. Diabetes Care 2006; 29 (5): 1016-23. (Pubitemid 44115238)
100. Nissen SE, Wolski K, Topol EJ. Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus. JAMA 2005; 294 (20): 2581-6. (Pubitemid 41697247)
101. Piccinni C, Motola D, Marchesini G, Poluzzi E. Assessing the association of pioglitazone use and bladder cancer through drug adverse event reporting. Diabetes Care 2011; 34 (6): 1369-71.
102. Henry RR, Lincoff AM, Mudaliar S, Rabbia M, Chognot C, Herz M. Effect of the dual peroxisome proliferator-activated receptor-alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study. Lancet 2009; 374 (9684): 126-35.
103. Hoffman LaRoche. A safety and efficacy study to evaluate the potential of aleglitazar to reduce cardiovascular risk in coronary heart disease (CHD) patients with a recent acute coronary syndrome (ACS) event and Type 2 Diabetes Melitus (T2D). ClinicalTrials.Gov 2011 February 15 [cited 2011 Oct 10]; Available from: URL: (accessed 10 October 2011).
104. Ooi EM, Watts GF, Sprecher DL, Chan DC, Barrett PH. Mechanism of action of a peroxisome proliferator-activated receptor (PPAR)-{delta} agonist on lipoprotein metabolism in dyslipidemic subjects with central obesity. J Clin Endocrinol Metab 2011; 96 (10): E1568-76.
105. Cariou B, Zair Y, Staels B, Bruckert E. Effects of the new dual PPAR alpha/delta agonist GFT505 on lipid and glucose homeostasis in abdominally obese patients with combined dyslipidemia or impaired glucose metabolism. Diabetes Care 2011; 34 (9): 2008-14.
106. Bailey D, Jahagirdar R, Gordon A, et al., RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo. J Am Coll Cardiol 2010; 55 (23): 2580-9.
107. Nicholls SJ, Gordon A, Johansson J, et al., Efficacy and safety of a novel oral inducer of apolipoprotein a-I synthesis in statin-treated patients with stable coronary artery disease a randomized controlled trial. J Am Coll Cardiol 2011; 57 (9): 1111-9.
108. Nissen SE, Tsunoda T, Tuzcu EM, et al., 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. (Pubitemid 37430562)
109. Nicholls SJ, Tuzcu EM, Sipahi I, et al., Relationship between atheroma regression and change in lumen size after infusion of apolipoprotein A-I Milano. J Am Coll Cardiol 2006; 47 (5): 992-7.
110. Tardif JC, Gregoire J, L'Allier PL, et al., Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 2007; 297 (15): 1675-82. (Pubitemid 46631626)
111. Navab M, Anantharamaiah GM, Hama S, et al., Oral administration of an Apo A-I mimetic Peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol. Circulation 2002; 105 (3): 290-2. (Pubitemid 34106174)
112. Bielicki JK, Zhang H, Cortez Y, et al., A new HDL mimetic peptide that stimulates cellular cholesterol efflux with high efficiency greatly reduces atherosclerosis in mice. J Lipid Res 2010; 51 (6): 1496-503.
113. Cerenis Therapeutics SA. CHI SQUARE: Can HDL Infusions Significantly Quicken Atherosclerosis Regression? A Phase II, Multi-Center, Double-Blind, Ascending Dose, Placebo-Controlled, Dose-Finding Trial of CER-001 or Placebo in Subjects With Acute Coronary Syndrome. ClinicalTrials.Gov 2011 September 28 [cited 2011 Oct 10]; Available from: URL: (accessed 10 October 2011).
114. Sacks FM, Rudel LL, Conner A, et al., Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo. J Lipid Res 2009; 50 (5): 894-907.
115. Waksman R, Torguson R, Kent KM, et al., A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high-density lipoprotein plasma infusions in patients with acute coronary syndrome. J Am Coll Cardiol 2010; 55 (24): 2727-35.
116. Packard CJ. Lipoprotein-associated phospholipase A2 as a biomarker of coronary heart disease and a therapeutic target. Curr Opin Cardiol 2009; 24 (4): 358-63.
117. Serruys PW, Garcia-Garcia HM, Buszman P, et al., Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation 2008; 118 (11): 1172-82.
118. GlaxoSmithKline. The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY). ClinicalTrials Gov. 6 October 2011. (accessed October 2011).
119. GlaxoSmithKline. The Stabilization Of pLaques usIng Darapladib- Thrombolysis In Myocardial Infarction 52 Trial (SOLID-TIMI 52). ClinicalTrials Gov. 6 October 2011. (accessed October 2011).
120. Rosenson RS, Hislop C, Elliott M, Stasiv Y, Goulder M, Waters D. Effects of varespladib methyl on biomarkers and major cardiovascular events in acute coronary syndrome patients. J Am Coll Cardiol 2010; 56 (14): 1079-88.
121. Rosenson RS, Elliott M, Stasiv Y, Hislop C. Randomized trial of an inhibitor of secretory phospholipase A2 on atherogenic lipoprotein subclasses in statin-treated patients with coronary heart disease. Eur Heart J 2011; 32 (8): 999-1005.
122. Dzavik V, Lavi S, Thorpe K, et al., The sPLA2 inhibition to decrease enzyme release after percutaneous coronary intervention (SPIDER-PCI) trial. Circulation 2010; 122 (23): 2411-8.
123. Anthera Pharmaceuticals. VISTA-16 Trial: Evaluation of Safety and Efficacy of Short-term A-002 Treatment in Subjects With Acute Coronary Syndrome. ClinicalTrials Gov. 11 October 2011. (accessed October 2011).
124. Walldius G, Erikson U, Olsson AG, et al., The effect of probucol on femoral atherosclerosis: the Probucol Quantitative Regression Swedish Trial (PQRST). Am J Cardiol 1994; 74 (9): 875-83. (Pubitemid 24340308)
125. Tardif JC, McMurray JJ, Klug E, et al., Effects of succinobucol (AGI-1067) after an acute coronary syndrome: a randomised, double-blind, placebo-controlled trial. Lancet 2008; 371 (9626): 1761-8. (Pubitemid 351697951)
126. Nguyen TH, Mainot S, Lainas P, et al., Ex vivo liver-directed gene therapy for the treatment of metabolic diseases: advances in hepatocyte transplantation and retroviral vectors. Curr Gene Ther 2009; 9 (2): 136-49.
127. Al-Allaf FA, Coutelle C, Waddington SN, David AL, Harbottle R, Themis M. LDLR-Gene therapy for familial hypercholesterolaemia: problems, progress, and perspectives. Int Arch Med 2010; 3: 36.
128. Gaudet D, de WJ, Tremblay K, et al., Review of the clinical development of alipogene tiparvovec gene therapy for lipoprotein lipase deficiency. Atheroscler Suppl 2010; 11 (1): 55-60.
129. Franssen R, Gaudet D, Stroes ES, et al., AAV1-LPLS447X gene therapy with alipogene tiparvovec prevents pancreatitis in lipoprotein lipase deficiency. Circulation 2009; 120 (Suppl.): S591-2 [abstract].
130. Carpentier A, Frisch F, Labbe SM, et al., Gene therapy with alipogene tiparvovec results in enhanced post-prandial clearance of low density chylomicrons in LPLD patients. Circulation 2010; 122 (21 Suppl.): A16900 [abstract].
131. Gaudet D, Methot J, Gagne C, et al., Modifications in triglyceride-rich lipoprotein metabolism induced by alipogene tiparvovec (AAV1-LPLS447X Gene Therapy) correlate with clinical benefit in patients with lipoprotein lipase deficiency (LPLD). Circulation 2010; 122 (21 Suppl.): A21355 [abstract].
132. Malekzadeh F, Marshall T, Pourshams A, et al., A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy ('polypill') on cardiovascular risk factors. Int J Clin Pract 2010; 64 (9): 1220-7.
133. Yusuf S, Pais P, Afzal R, et al., Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial. Lancet 2009; 373 (9672): 1341-51.