The promise of cholesteryl ester transfer protein (CETP) inhibition in the treatment of cardiovascular disease

Current Pharmaceutical Design

Volumn 19, Issue 17, 2013, Pages 3143-3149

  Bochem, A E ^a   Kuivenhoven, J A ^b   Stroes, E S G ^a  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

^b UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

Author keywords

Atherosclerosis; Cardiovascular risk; Cholesterol; Dyslipidemia; HDL; lDL; Lipids; Lipoproteins

Indexed keywords

ANACETRAPIB; BAY 60 5521; CHOLESTEROL ESTER TRANSFER PROTEIN; DALCETRAPIB; EVACETRAPIB; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; TORCETRAPIB; UNCLASSIFIED DRUG;

ATHEROGENESIS; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CLINICAL TRIAL (TOPIC); DRUG EFFECT; DRUG EFFICACY; DRUG TOLERABILITY; GENETICS; HUMAN; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW;

ANIMALS; BENZODIAZEPINES; CARDIOVASCULAR DISEASES; CHOLESTEROL ESTER TRANSFER PROTEINS; CHOLESTEROL, HDL; HUMANS; OXAZOLIDINONES;

EID: 84878645607     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612811319170022     Document Type: Review

References (125)

1. Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997; 349(9063): 1436-42.
2. Bethesda MdnHLaBI. National Cholesterol Education Program. Second report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). NIH publication no. 93-3095. 2012. NIH publication no. 93-3095. 1993.
3. Baigent C, Keech A, Kearney PM, et al. 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.
4. Grundy SM, Cleeman JI, Merz CN, et al. 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.
5. Smith SC, Jr., Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation 2006; 113(19): 2363-72.
6. Poss J, Custodis F, Werner C, Weingartner O, Bohm M, Laufs U. Cardiovascular disease and dyslipidemia: beyond LDL. Curr Pharm Des 2011; 17(9): 861-70.
7. Gordon DJ, Probstfield JL, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 1989; 79(1): 8-15.
8. Assmann G, Schulte H. Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Prospective Cardiovascular Munster study. Am J Cardiol 1992; 70(7): 733-7.
9. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1977; 62(5): 707-14.
10. Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007; 357(13): 1301-10.
11. Nicholls SJ, Tuzcu EM, Sipahi I, Grasso AW, Schoenhagen P, Hu T, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA 2007; 297(5): 499-508.
12. Jafri H, Alsheikh-Ali AA, Karas RH. Meta-analysis: statin therapy does not alter the association between low levels of high-density lipoprotein cholesterol and increased cardiovascular risk. Ann Intern Med 2010; 153(12): 800-8.
13. Vergeer M, Holleboom AG, Kastelein JJ, Kuivenhoven JA. The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis? J Lipid Res 2010; 51(8): 2058-73.
14. Willer CJ, Sanna S, Jackson AU, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 2008; 40(2): 161-9.
15. Voight BF, Peloso GM, Orho-Melander M, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 2012.
16. Trigatti BL, Krieger M, Rigotti A. Influence of the HDL receptor SR-BI on lipoprotein metabolism and atherosclerosis. Arterioscler Thromb Vasc Biol 2003; 23(10): 1732-8.
17. Connelly PW, Hegele RA. Hepatic lipase deficiency. Crit Rev Clin Lab Sci 1998; 35(6): 547-72.
18. Berard AM, Foger B, Remaley A, et al. High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithin-cholesteryl acyltransferase. Nat Med 1997; 3(7): 744-9.
19. Westerterp M, van der Hoogt CC, de HW, et al. Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice. Arterioscler Thromb Vasc Biol 2006; 26(11): 2552-9.
20. Rubin EM, Krauss RM, Spangler EA, Verstuyft JG, Clift SM. Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI. Nature 1991; 353(6341): 265-7.
21. Paszty C, Maeda N, Verstuyft J, Rubin EM. Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice. J Clin Invest 1994; 94(2): 899-903.
22. Choudhury RP, Rong JX, Trogan E, et al. High-density lipoproteins retard the progression of atherosclerosis and favorably remodel lesions without suppressing indices of inflammation or oxidation. Arterioscler Thromb Vasc Biol 2004; 24(10): 1904-9.
23. Rong JX, Li J, Reis ED, et al. Elevating high-density lipoprotein cholesterol in apolipoprotein E-deficient mice remodels advanced atherosclerotic lesions by decreasing macrophage and increasing smooth muscle cell content. Circulation 2001; 104(20): 2447-52.
24. Benoit P, Emmanuel F, Caillaud JM, et al. Somatic gene transfer of human ApoA-I inhibits atherosclerosis progression in mouse models. Circulation 1999; 99(1): 105-10.
25. Furbee JW, Jr., Parks JS. Transgenic overexpression of human lecithin: cholesterol acyltransferase (LCAT) in mice does not increase aortic cholesterol deposition. Atherosclerosis 2002; 165(1): 89-100.
26. Mehlum A, Gjernes E, Solberg LA, Hagve TA, Prydz H. Overexpression of human lecithin: cholesterol acyltransferase in mice offers no protection against diet-induced atherosclerosis. APMIS 2000; 108(5): 336-42.
27. Hoeg JM, Santamarina-Fojo S, Berard AM, Cornhill JF, Herderick EE, Feldman SH, et al. Overexpression of lecithin: cholesterol acyltransferase in transgenic rabbits prevents diet-induced atherosclerosis. Proc Natl Acad Sci U S A 1996 Oct 15; 93(21): 11448-53.
28. Brousseau ME, Santamarina-Fojo S, Vaisman BL, et al. Overexpression of human lecithin: cholesterol acyltransferase in cholesterol-fed rabbits: LDL metabolism and HDL metabolism are affected in a gene dose-dependent manner. J Lipid Res 1997; 38(12): 2537-47.
29. Dichek HL, Qian K, Agrawal N. Divergent effects of the catalytic and bridging functions of hepatic lipase on atherosclerosis. Arterioscler Thromb Vasc Biol 2004; 24(9): 1696-702.
30. Mezdour H, Jones R, Dengremont C, Castro G, Maeda N. Hepatic lipase deficiency increases plasma cholesterol but reduces susceptibility to atherosclerosis in apolipoprotein E-deficient mice. J Biol Chem 1997 May 23; 272(21): 13570-5.
31. Freeman L, Amar MJ, Shamburek R, et al. Lipolytic and ligandbinding functions of hepatic lipase protect against atherosclerosis in LDL receptor-deficient mice. J Lipid Res 2007; 48(1): 104-13.
32. Trigatti BL, Krieger M, Rigotti A. Influence of the HDL receptor SR-BI on lipoprotein metabolism and atherosclerosis. Arterioscler Thromb Vasc Biol 2003; 23(10): 1732-8.
33. Joyce CW, Wagner EM, Basso F, et al. ABCA1 overexpression in the liver of LDLr-KO mice leads to accumulation of proatherogenic lipoproteins and enhanced atherosclerosis. J Biol Chem 2006; 281(44): 33053-65.
34. Joyce CW, Amar MJ, Lambert G, et al. The ATP binding cassette transporter A1 (ABCA1) modulates the development of aortic atherosclerosis in C57BL/6 and apoE-knockout mice. Proc Natl Acad Sci U S A 2002; 99(1): 407-12.
35. Singaraja RR, Fievet C, Castro G, James ER, Hennuyer N, Clee SM, et al. Increased ABCA1 activity protects against atherosclerosis. J Clin Invest 2002; 110(1): 35-42.
36. Hovingh GK, Brownlie A, Bisoendial RJ, et al. A novel apoA-I mutation (L178P) leads to endothelial dysfunction, increased arterial wall thickness, and premature coronary artery disease. J Am Coll Cardiol 2004; 44(7): 1429-35.
37. Klos KL, Kullo IJ. Genetic determinants of HDL: monogenic disorders and contributions to variation. Curr Opin Cardiol 2007; 22(4): 344-51.
38. Strang AC, Hovingh GK, Stroes ES, Kastelein JJ. The genetics of high-density lipoprotein metabolism: clinical relevance for therapeutic approaches. Am J Cardiol 2009; 104(10 Suppl): 22E-31E.
39. Schaefer EJ, Heaton WH, Wetzel MG, Brewer HB, Jr. Plasma apolipoprotein A-1 absence associated with a marked reduction of high density lipoproteins and premature coronary artery disease. Arteriosclerosis 1982; 2(1): 16-26.
40. Frikke-Schmidt R, Nordestgaard BG, Schnohr P, Steffensen R, Tybjaerg-Hansen A. Mutation in ABCA1 predicted risk of ischemic heart disease in the Copenhagen City Heart Study Population. J Am Coll Cardiol 2005; 46(8): 1516-20.
41. Frikke-Schmidt R, Nordestgaard BG, et al. Association of loss-offunction mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease. JAMA 2008; 299(21): 2524-32.
42. Hovingh GK, Hutten BA, Holleboom AG, et al. Compromised LCAT function is associated with increased atherosclerosis. Circulation 2005; 112(6): 879-84.
43. Calabresi L, Baldassarre D, Simonelli S, Gomaraschi M, Amato M, Castelnuovo S, et al. Plasma lecithin: cholesterol acyltransferase and carotid intima-media thickness in European individuals at high cardiovascular risk. J Lipid Res 2011; 52(8): 1569-74.
44. Bochem AE, van Wijk DF, Holleboom AG, et al. ABCA1 mutation carriers with low high-density lipoprotein cholesterol are characterized by a larger atherosclerotic burden. Eur Heart J 2012 Nov 7.
45. Duivenvoorden R, Holleboom AG, van den Bogaard B, et al. Cholesterol acyltransferase gene mutations have accelerated atherogenesis as assessed by carotid 3.0-T magnetic resonance imaging carriers of lecithin. J Am Coll Cardiol 2011; 58(24): 2481-7.
46. Haase CL, Tybjaerg-Hansen A, Qayyum AA, Schou J, Nordestgaard BG, Frikke-Schmidt R. LCAT, HDL cholesterol and ischemic cardiovascular disease: a Mendelian randomization study of HDL cholesterol in 54,500 individuals. J Clin Endocrinol Metab 2012; 97(2): E248-E256.
47. Vergeer M, Cohn DM, Boekholdt SM, et al. Lack of association between common genetic variation in endothelial lipase (LIPG) and the risk for CAD and DVT. Atherosclerosis 2010; 211(2): 558-64.
48. Andersen RV, Wittrup HH, Tybjaerg-Hansen A, Steffensen R, Schnohr P, Nordestgaard BG. Hepatic lipase mutations, elevated high-density lipoprotein cholesterol, and increased risk of ischemic heart disease: the Copenhagen City Heart Study. J Am Coll Cardiol 2003; 41(11): 1972-82.
49. Johannsen TH, Kamstrup PR, Andersen RV, Jensen GB, Sillesen H, Tybjaerg-Hansen A, et al. Hepatic lipase, genetically elevated high-density lipoprotein, and risk of ischemic cardiovascular disease. J Clin Endocrinol Metab 2009; 94(4): 1264-73.
50. van Acker BA, Botma GJ, Zwinderman AH, et al. High HDL cholesterol does not protect against coronary artery disease when associated with combined cholesteryl ester transfer protein and hepatic lipase gene variants. Atherosclerosis 2008; 200(1): 161-7.
51. Pollex RL, Hegele RA. Genetic determinants of plasma lipoproteins. Nat Clin Pract Cardiovasc Med 2007; 4(11): 600-9.
52. Tall AR. An overview of reverse cholesterol transport. Eur Heart J 1998; 19 Suppl A: A31-A35.
53. Besler C, Luscher TF, Landmesser U. Molecular mechanisms of vascular effects of High-density lipoprotein: alterations in cardiovascular disease. EMBO Mol Med 2012; 4(4): 251-68.
54. van Leuven SI, Birjmohun RS, Franssen R, et al. ApoAIphosphatidylcholine infusion neutralizes the atherothrombotic effects of C-reactive protein in humans. J Thromb Haemost 2009; 7(2): 347-54.
55. Nieuwdorp M, Vergeer M, Bisoendial RJ, et al. Reconstituted HDL infusion restores endothelial function in patients with type 2 diabetes mellitus. Diabetologia 2008; 51(6): 1081-4.
56. Barter PJ, Puranik R, Rye KA. New insights into the role of HDL as an anti-inflammatory agent in the prevention of cardiovascular disease. Curr Cardiol Rep 2007 Nov; 9(6): 493-8.
57. Mineo C, Deguchi H, Griffin JH, Shaul PW. Endothelial and antithrombotic actions of HDL. Circ Res 2006 Jun 9; 98(11): 1352-64.
58. Besler C, Heinrich K, Riwanto M, Luscher TF, Landmesser U. High-density lipoprotein-mediated anti-atherosclerotic and endothelial-protective effects: a potential novel therapeutic target in cardiovascular disease. Curr Pharm Des 2010 May; 16(13): 1480-93.
59. van Oostrom O, Nieuwdorp M, Westerweel PE, Hoefer IE, Basser R, Stroes ES, et al. Reconstituted HDL increases circulating endothelial progenitor cells in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 2007 Aug; 27(8): 1864-5.
60. Nicholls SJ, Hazen SL. Myeloperoxidase and cardiovascular disease. Arterioscler Thromb Vasc Biol 2005 Jun; 25(6): 1102-11.
61. Navab M, Ananthramaiah GM, Reddy ST, Van Lenten BJ, Ansell BJ, Fonarow GC, et al. The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res 2004 Jun; 45(6): 993-1007.
62. Uchida K, Kanematsu M, Morimitsu Y, Osawa T, Noguchi N, Niki E. Acrolein is a product of lipid peroxidation reaction. Formation of free acrolein and its conjugate with lysine residues in oxidized low density lipoproteins. J Biol Chem 1998 Jun 26; 273(26): 16058-66.
63. Proudfoot JM, Barden AE, Loke WM, Croft KD, Puddey IB, Mori TA. HDL is the major lipoprotein carrier of plasma F2-isoprostanes. J Lipid Res 2009 Apr; 50(4): 716-22.
64. Besler C, Heinrich K, Rohrer L, Doerries C, Riwanto M, Shih DM, et al. Mechanisms underlying adverse effects of HDL on eNOSactivating pathways in patients with coronary artery disease. J Clin Invest 2011 Jul; 121(7): 2693-708.
65. Schwartz GG. New horizons for cholesterol ester transfer protein inhibitors. Curr Atheroscler Rep 2012 Feb; 14(1): 41-8.
66. Vergeer M, Korporaal SJ, Franssen R, Meurs I, Out R, Hovingh GK, et al. Genetic variant of the scavenger receptor BI in humans. N Engl J Med 2011 Jan 13; 364(2): 136-45.
67. Khera AV, Cuchel M, Llera-Moya M, Rodrigues A, Burke MF, Jafri K, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med 2011 Jan 13; 364(2): 127-35.
68. Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy. N Engl J Med 2011 Nov 15.
69. Ginsberg HN, Elam MB, Lovato LC, Crouse JR, III, Leiter LA, Linz P, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010 Apr 29; 362(17): 1563-74.
70. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005 Nov 26; 366(9500): 1849-61.
71. Bloomgarden Z, Handelsman Y. Did AIM-HIGH aim too low? J Diabetes 2011 Dec 5.
72. Hovingh GK, Bochem AE, Kastelein JJ. Apolipoprotein A-I mimetic peptides. Curr Opin Lipidol 2010 Dec; 21(6): 481-6.
73. Barter PJ, Jones ME. Kinetic studies of the transfer of esterified cholesterol between human plasma low and high density lipoproteins. J Lipid Res 1980 Feb; 21(2): 238-49.
74. Barter PJ, Hopkins GJ, Calvert GD. Transfers and exchanges of esterified cholesterol between plasma lipoproteins. Biochem J 1982 Oct 15; 208(1): 1-7.
75. Inazu A, Brown ML, Hesler CB, Agellon LB, Koizumi J, Takata K, et al. Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Engl J Med 1990 Nov 1; 323(18): 1234-8.
76. Koizumi J, Mabuchi H, Yoshimura A, Michishita I, Takeda M, Itoh H, et al. Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia. Atherosclerosis 1985 Dec; 58(1-3): 175-86.
77. Yamashita S, Matsuzawa Y, Okazaki M, Kako H, Yasugi T, Akioka H, et al. Small polydisperse low density lipoproteins in familial hyperalphalipoproteinemia with complete deficiency of cholesteryl ester transfer activity. Atherosclerosis 1988 Mar; 70(1-2): 7-12.
78. Ha YC, Barter PJ. Differences in plasma cholesteryl ester transfer activity in sixteen vertebrate species. Comp Biochem Physiol B 1982; 71(2): 265-9.
79. Okamoto H, Yonemori F, Wakitani K, Minowa T, Maeda K, Shinkai H. A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature 2000 Jul 13; 406(6792): 203-7.
80. Morehouse LA, Sugarman ED, Bourassa PA, Sand TM, Zimetti F, Gao F, et al. Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits. J Lipid Res 2007 Jun; 48(6): 1263-72.
81. Sugano M, Makino N, Sawada S, Otsuka S, Watanabe M, Okamoto H, et al. Effect of antisense oligonucleotides against cholesteryl ester transfer protein on the development of atherosclerosis in cholesterol-fed rabbits. J Biol Chem 1998 Feb 27; 273(9): 5033-6.
82. Curb JD, Abbott RD, Rodriguez BL, Masaki K, Chen R, Sharp DS, et al. A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly. J Lipid Res 2004; 45(5): 948-53.
83. Moriyama Y, Okamura T, Inazu A, et al. A low prevalence of coronary heart disease among subjects with increased high-density lipoprotein cholesterol levels, including those with plasma cholesteryl ester transfer protein deficiency. Prev Med 1998; 27(5 Pt 1): 659-67.
84. Zhong S, Sharp DS, Grove JS, et al. Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels. J Clin Invest 1996; 97(12): 2917-23.
85. Kakko S, Tamminen M, Kesaniemi YA, Savolainen MJ. R451Q mutation in the cholesteryl ester transfer protein (CETP) gene is associated with high plasma CETP activity. Atherosclerosis 1998; 136(2): 233-40.
86. Tsai MY, Johnson C, Kao WH, Sharrett AR, Arends VL, Kronmal R, et al. Cholesteryl ester transfer protein genetic polymorphisms, HDL cholesterol, and subclinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis 2008; 200(2): 359-67.
87. Thompson A, Di AE, Sarwar N, et al. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA 2008; 299(23): 2777-88.
88. Agerholm-Larsen B, Nordestgaard BG, Steffensen R, Jensen G, Tybjaerg-Hansen A. Elevated HDL cholesterol is a risk factor for ischemic heart disease in white women when caused by a common mutation in the cholesteryl ester transfer protein gene. Circulation 2000; 101(16): 1907-12.
89. Ridker PM, Pare G, Parker AN, Zee RY, Miletich JP, Chasman DI. Polymorphism in the CETP gene region, HDL cholesterol, and risk of future myocardial infarction: Genomewide analysis among 18 245 initially healthy women from the Women's Genome Health Study. Circ Cardiovasc Genet 2009; 2(1): 26-33.
90. Thompson A, Di AE, Sarwar N, et al. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA 2008; 299(23): 2777-88.
91. Boekholdt SM, Kuivenhoven JA, Wareham NJ, et al. Plasma levels of cholesteryl ester transfer protein and the risk of future coronary artery disease in apparently healthy men and women: the prospective EPIC (European Prospective Investigation into Cancer and nutrition)-Norfolk population study. Circulation 2004; 110(11): 1418-23.
92. Ranalletta M, Bierilo KK, Chen Y, et al. Biochemical characterization of cholesteryl ester transfer protein inhibitors. J Lipid Res 2010; 51(9): 2739-52.
93. Niesor EJ, Magg C, Ogawa N, Okamoto H, von der ME, Matile H, et al. Modulating cholesteryl ester transfer protein activity maintains efficient pre-beta-HDL formation and increases reverse cholesterol transport. J Lipid Res 2010 Dec; 51(12): 3443-54.
94. Davidson MH. Update on CETP inhibition. J Clin Lipidol 2010; 4(5): 394-8.
95. Barter PJ, Rye KA. Cholesteryl ester transfer protein inhibition as a strategy to reduce cardiovascular risk. J Lipid Res 2012; 53(9): 1755-66.
96. 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.
97. Johns DG, Duffy J, Fisher T, Hubbard BK, Forrest MJ. On-and off-target pharmacology of torcetrapib: current understanding and implications for the structure activity relationships (SAR), discovery and development of cholesteryl ester-transfer protein (CETP) inhibitors. Drugs 2012; 72(4): 491-507.
98. Forrest MJ, Bloomfield D, Briscoe RJ, et al. 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.
99. Blasi E, Bamberger M, Knight D, et al. Effects of CP-532,623 and torcetrapib, cholesteryl ester transfer protein inhibitors, on arterial blood pressure. J Cardiovasc Pharmacol 2009; 53(6): 507-16.
100. Vergeer M, Stroes ES. The pharmacology and off-target effects of some cholesterol ester transfer protein inhibitors. Am J Cardiol 2009; 104(10 Suppl): 32E-8E.
101. Nissen SE, Tardif JC, Nicholls SJ, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med 2007; 356(13): 1304-16.
102. Stroes ES, Kastelein JJ, Benardeau A, et al. Dalcetrapib: no offtarget toxicity on blood pressure or on genes related to the reninangiotensin-aldosterone system in rats. Br J Pharmacol 2009; 158(7): 1763-70.
103. Bots ML, Visseren FL, Evans GW, et al. Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. Lancet 2007; 370(9582): 153-60.
104. Kastelein JJ, van Leuven SI, Burgess L, et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med 2007; 19; 356(16): 1620-30.
105. Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med 2007; 356(13): 1304-16.
106. 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.
107. Noghero A, Perino A, Seano G, et al. Liver X receptor activation reduces angiogenesis by impairing lipid raft localization and signaling of vascular endothelial growth factor receptor-2. Arterioscler Thromb Vasc Biol 2012; 32(9): 2280-8.
108. de Haan W, de Vries-van der Weij, van der Hoorn JW, et al. Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin. Circulation 2008 May 13; 117(19): 2515-22.
109. Westerterp M, Gourion-Arsiquaud S, Murphy AJ, Shih A, Cremers S, Levine RL, et al. Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol efflux pathways. Cell Stem Cell 2012; 11(2): 195-206.
110. Stroes ES, Kastelein JJ, Benardeau A, et al. Dalcetrapib: no offtarget toxicity on blood pressure or on genes related to the reninangiotensin-aldosterone system in rats. Br J Pharmacol 2009; 158(7): 1763-70.
111. Stein EA, Stroes ES, Steiner G, et al. Safety and tolerability of dalcetrapib. Am J Cardiol 2009; 104(1): 82-91.
112. Luscher TF, Taddei S, Kaski JC, et al. Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease: the dal-VESSEL randomized clinical trial. Eur Heart J 2012; 33(7): 857-65.
113. 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.
114. Cao G, Beyer TP, Zhang Y, Schmidt RJ, Chen YQ, Cockerham SL, et al. Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure. J Lipid Res 2011; 52(12): 2169-76.
115. 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.
116. 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.
117. Schwartz GG, Olsson AG, Abt M, et al. Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome. N Engl J Med 2012 Nov 5.
118. 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.
119. Tall AR. The effects of cholesterol ester transfer protein inhibition on cholesterol efflux. Am J Cardiol 2009; 104(10 Suppl): 39E-45E.
120. Yvan-Charvet L, Kling J, Pagler T, et al. Cholesterol efflux potential and antiinflammatory properties of high-density lipoprotein after treatment with niacin or anacetrapib. Arterioscler Thromb Vasc Biol 2010; 30(7): 1430-8.
121. Horowitz JD, Rosenson RS, McMurray JJ, Marx N, Remme WJ. Clinical Trials Update AHA Congress 2010. Cardiovasc Drugs Ther 2011; 25(1): 69-76.
122. El Harchaoui K, Arsenault BJ, Franssen R, et al. High-density lipoprotein particle size and concentration and coronary risk. Ann Intern Med 2009; 150(2): 84-93.
123. Briel M, Ferreira-Gonzalez I, You JJ, et al. Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and metaregression analysis. BMJ 2009; 338: b92.
124. Landmesser U, von EA, Kastelein J, Deanfield J, Luscher TF. Increasing high-density lipoprotein cholesterol by cholesteryl ester transfer protein-inhibition: a rocky road and lessons learned? The early demise of the dal-HEART programme. Eur Heart J 2012; 33(14): 1712-5.
125. Johannsen TH, Frikke-Schmidt R, Schou J, Nordestgaard BG, Tybjaerg-Hansen A. Genetic Inhibition of CETP, Ischemic Vascular Disease and Mortality, and Possible Adverse Effects. J Am Coll Cardiol 2012; 60(20): 2041-8.