Systematic Review of CETP Inhibitors for Increasing High-Density Lipoprotein Cholesterol: Where Do These Agents Stand in the Approval Process?

American Journal of Therapeutics

Volumn 22, Issue 2, 2015, Pages 147-158

  Bishop, Bryan M ^a  

^a SUMMA HEALTH SYSTEM   (United States)

Author keywords

anacetrapib; CETP; CETP inhibitors; dalcetrapib; evacetrapib; HDL; lipids; torcetrapib

Indexed keywords

ANACETRAPIB; DALCETRAPIB; EVACETRAPIB; FIBRIC ACID DERIVATIVE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; MONOUNSATURATED FATTY ACID; NICOTINIC ACID; POLYUNSATURATED FATTY ACID; TORCETRAPIB; CHOLESTEROL ESTER TRANSFER PROTEIN; HYPOCHOLESTEROLEMIC AGENT;

ACUTE CORONARY SYNDROME; ALCOHOL CONSUMPTION; ARTICLE; DRUG APPROVAL; HUMAN; LIPID METABOLISM; MORTALITY; MULTICENTER STUDY (TOPIC); PATHOPHYSIOLOGY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SMOKING CESSATION; SYSTEMATIC REVIEW (TOPIC); WEIGHT REDUCTION; ANIMAL; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL (TOPIC); DRUG EFFECTS;

ANIMALS; ANTICHOLESTEREMIC AGENTS; CHOLESTEROL ESTER TRANSFER PROTEINS; CHOLESTEROL, HDL; CLINICAL TRIALS AS TOPIC; DRUG APPROVAL; HUMANS;

EID: 84925259873     PISSN: 10752765     EISSN: 15363686     Source Type: Journal    
DOI: 10.1097/MJT.0b013e31828b8463     Document Type: Article

References (78)

1. Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.
2. Boekholdt SM, Arsenault BJ, Mora S, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA. 2012;307:1302-1309.
3. 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;360:7-22.
4. Wilson PWF, D' Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837-1847.
5. Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357:1301-1310.
6. Gordon DJ, Probstfield JL, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation. 1989;79:8-15.
7. Singh IM, Shishehbor MH, Ansell BJ. High-density lipoprotein as a therapeutic target: a systematic review. JAMA. 2007;298:786-798.
8. th ed. Philadelphia, PA: Saunders Elsevier; 2012:975-995.
9. Weber O, Bischoff H, Schmeck C, et al. Cholesteryl ester transfer protein and its inhibition. Cell Mol Life Sci. 2010; 67:3139-3149.
10. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third national health and nutrition examination survey. JAMA. 2002;287:356-359.
11. Castelli WP, Garrison RJ, Wilson PWF, et al. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham study. JAMA. 1986;256:2835-2838.
12. Frick MH, Elo O, Haapa K, et al. Helsinki heart study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. N Engl JMed. 1987;317:1237-1245.
13. Miller NE, Thelle DS, Førde OH, et al. The Tromsø heartstudy: high-density lipoprotein and coronary heart-disease: a prospective case-control study. Lancet. 1977;309:965-968.
14. Gordon DJ, Rifkind BM. High-density lipoprotein - the clinical implications of recent studies. N Engl J Med. 1989; 321:1311-1316.
15. Stefanick ML, Mackey S, Sheehan M, et al. Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol. N Engl J Med. 1998;339:12-20.
16. Kraus WE, Houmard JA, Duscha BD, et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med. 2002;347:1483-1492.
17. Maeda K, Noguchi Y, Fukui T. The effects of cessation from cigarette smoking on the lipid and lipoprotein profiles: a meta-analysis. Prev Med. 2003;37:283-290.
18. Wadden TA, Volger S, Sarwer DB, et al. A two-year randomized trial of obesity treatment in primary care practice. N Engl J Med. 2011;365:1969-1979.
19. Despres J-P, Golay A, Sjostrom L. Effect of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005;353:2121-2134.
20. Gaziano JM, Buring JE, Breslow JL, et al. Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction. N Engl J Med. 1993;329:1829-1834.
21. Mensink RP, Zock PL, Kester ADM, et al. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003;77:1146-1155.
22. Daviglus ML, Stamler J, Orencia AJ, et al. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med. 1997;336:1046-1053.
23. Niaspan [package insert]. North Chicago, IL: Abbott Laboratories; 2010.
24. Tricor [package insert]. North Chicago, IL: Abbott Laboratories; 2011.
25. Crestor [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2012.
26. The Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease. JAMA. 1975;231:360-381.
27. Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in coronary drug project patients: long-term benefits with niacin. J Am Coll Cardiol. 1986;8:1245-1255.
28. 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;223:405-418.
29. Brown BG, Zhao XQ, Chait A, et al. Simvastatin, niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345;1583-1592.
30. Whitney EJ, Krasuski RA, Personius BE, et al. A randomized trial of a strategy for increasing high-density lipoprotein cholesterol levels: effects on progression of coronary heart disease and clinical events. Ann Intern Med. 2005;142:95-104.
31. The AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255-2267.
32. Arthur JB, Ashby DWR, Bremer C, et al. Trial of clofibrate in the treatment of ischaemic heart disease: five-year study by a group of physicians of the Newcastle Upon Tyne region. Br Med J. 1971;4:767-775.
33. Oliver MF, Alstead S, Aitchison JD, et al. Ischaemic heart disease: a secondary prevention trial using clofibrate: report by the research committee of the Scottish Society of Physicians. Br Med J. 1971;4:775-784.
34. Oliver MF, Heady JA, Morris JN, et al. A co-operative in the primary prevention of ischaemic heart disease using clofibrate: report from the committee of principal investigators. Br Heart J. 1978;40:1069-1118.
35. Oliver MF, Heady JA, Morris JN, et al. WHO cooperative trial on primary prevention of iscaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up: report of the committee of principal investigators. Lancet. 1984;2:600-604.
36. Rubins HB, Robins SJ, Collins D, et al. Veterans affairs highdensity lipoprotein cholesterol intervention trial study group. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med. 1999;341:410-418.
37. The BIP Study Group. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation. 2000;102:21-27.
38. Meade T, Zuhrie R, Cook C, et al. Bezafibrate in men with lower extremity arterial disease: randomized controlled trial. BMJ. 2002;325:1139.
39. Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes (the FIELD study): randomized controlled trial. Lancet. 2005;366:1849-1861.
40. Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990;323:1289-1298.
41. Taylor AJ, Sullenberger LE, Lee HJ, et al. 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 athersclerosis progression in secondary prevention patients treated with statins. Circulation. 2004;110:3512-3517.
42. Merck. Merck announces HPS2-THRIVE study of Tredaptive (extended-release niacin/laropiprant) did not achieve primary endpoint. Available at: http://medlib. bu.edu/facts/faq2.cfm/content/citationsama.cfm. Accessed December 20, 2012.
43. Grundy SM, Cleeman JI, Merz NB, et al. Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation. 2004;110;227-239.
44. The ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010; 362:1563-1574.
45. Inazu A, Brown ML, Hesler CB, et al. Increased highdensity lipoprotein levels caused by a common choles-teryl-ester transfer protein gene mutation. N Engl J Med. 1990;323:1234-1238.
46. Kathiresan S, Melander O, Anevski D, et al. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med. 2008;358:1240-1249.
47. Brousseau ME, Schaefer EJ, Wolfe ML, et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med. 2004;350:1505-1515.
48. Kastelein JJP, Van Leuven SI, Burgess L, et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med. 2007;356:1620-1630.
49. Bots ML, Visseren FL, Evans GW, et al. Torcetrapib and carotid intima-media thickness in mixed dyslipidemia (RADIANCE 2 study): a randomized, double-blind trial. Lancet. 2007;370:153-160.
50. Barter PJ, Caufield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109-2122.
51. Nissen SE, Tardif J-C, Nicholls SJ, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med. 2007;356:1304-1316.
52. Davidson MH, McKenney JM, Shear CL, et al. Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average highdensity lipoprotein cholesterol levels. J Am Coll Cardiol. 2006;48:1774-1781.
53. Clark RW, Sutfin TA, Ruggeri RB, et al. Raising high-density lipoprotein in humans through inhibition of cholesterly ester transfer protein: an initial multidose study of torcetrapib. Arterioscler Thromb Vasc Biol. 2004;24:490-497.
54. Barter P. Lessons learned from the investigation of lipid level management to understand its impact in atherosclerotic events (ILLUMINATE) trial. Am J Cardiol. 2009;104:10EE-15E.
55. 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;118:2515-2522.
56. Forrest MJ, Bloomfield D, Briscoe RJ, et al. Torcetrapibinduced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. Br J Pharmacol. 2008;154:1465-1473.
57. Schwartz GG, Olsson AG, Abt M, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367:2089-2099.
58. 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 randomized clinical trial. Lancet. 2011;378:1547-1559.
59. Luscher TF, Taddei S, Kaski J-C, 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;33:857-865.
60. Stein EA, Roth EM, Rhyne JM, et al. Safety and tolerability of dalcetrapib (RO4607381/JTT-705): results from a 48-week trial. Eur Heart J. 2010;31:480-488.
61. De Grooth GJ, Kuivenhoven JA, Stalenhoef AFH, et al. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation. 2002;105:2159-2165.
62. Kuivenhoven JA, de Grooth GJ, Mawamura H, et al. Effectiveness of inhibition of cholesteryl ester transfer protein by JTT-705 in combination with pravastatin in type II dyslipidemia. Am J Cardiol. 2005;95:1085-1088.
63. Ballantyne CM, Miller M, Niesor EJ, et al. Effect of dalcetrapib plus pravastatin on lipoprotein metabolism and high-density lipoprotein composition and function in dyslipidemic patients: results of a phase IIb dose-ranging study. Am Heart J. 2012;163:515-521.
64. Simic B, Hermann M, Shaw SG, et al. Torcetrapib impairs endothelial function in hypertension. Eur Heart J. 2012;33: 1615-1624.
65. Schwartz GG. New horizons for cholesterol ester transfer protein inhibitors. Curr Atheroscler Rep. 2012; 14:41-48.
66. Randomized EValuation of the Effects of Anacetrapib though Lipid modification (REVEAL) [NCT 01252953]. Available at: http://www.clinicaltrials.gov/ct2/show/ record/NCT01252953. Accessed December 21, 2012.
67. Study to assess the tolerability and efficacy of anacetrapib co-administered with statin in participants with heterozygous familial hypercholesterolemia (MK-0859-020 AM1) (REALIZE) [NCT1524289]. Available at: http://www. clinicaltrials.gov/ct2/show/NCT01524289. Accessed December 21, 2012.
68. A study of the safety and efficacy of anacetrapib (MK-0859) when added to ongoing statin therapy (MK-0859-021) [NCT01717300]. Available at: http://www.clinicaltrials. gov/ct2/show/NCT01717300. Accessed December 21, 2012.
69. A study of evacetrapib in high-risk vascular disease (ACCELERATE) [NCT01687998]. Available at: http://www.clinicaltrials.gov/ct2/show/ NCT01687998. Accessed December 21, 2012.
70. 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;363:2406-2415.
71. Krishna R, Anderson MS, Bergman AJ, et al. Effect of the cholesteryl ester transfer protein inhibitor anacetrapib, on lipoproteins in patients with dyslipidemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomized placebo-controlled phase I studies. Lancet. 2007;370:1907-1914.
72. Bloomfield D, Carlson GL, Sapre A, et al. Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients. Am Heart J. 2009; 157:352-360.
73. Cao G, Beyer TP, Zhang Y, 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;52:2169-2176.
74. Nicholls SJ, Brewer HB, Kastelein JJP, 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; 306:2099-2109.
75. Hoang A, Murphy AJ, Coughlan MT, et al. Advanced glycation of apolipoprotein A-I impairs its anti-atherogenic properties. Diabetologia. 2007;50:1770-1779.
76. Tall AR, Yvan-Charvey L, Wang N. The failure of torcetrapib: was it the molecule or the mechanism? Arterioscler Thromb Vasc Biol. 2007;27:257-260.
77. Natarajan P, Ray KK, Cannon CP. High-density lipoprotein and coronary heart disease: current and future therapies. J Am Coll Cardiol. 2010;55:1283-1299.
78. Tall AR, Yvan-Charvey L, Terasaka N, et al. ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis. Cell Metab. 2008;7:365-375.