American Journal of Cardiology
Volume 104, Issue 10, Supplement , Pages 10E-15E , 16 November 2009

Lessons Learned from the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) Trial

  • Philip Barter, MD, PhD

      Affiliations

    • Corresponding Author InformationAddress for reprints: Philip Barter, MD, PhD, The Heart Research Institute, 7 Eliza Street, Newtown, Sydney, New South Wales, Australia, 2042

References 

  1. Barter P, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komadja M, et al Effects of torcetrapib on morbidity and mortality in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–2122
  2. Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, et al. HDL cholesterol, very low levels of LDL cholesterol and cardiovascular events. N Engl J Med. 2007;357:1301–1310
  3. Barter PJ, Brewer HB, Chapman MJ, Hennekens CH, Rader DJ, Tall AR. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol. 2003;23:160–167
  4. 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;48:1782–1790
  5. Barter PJ, Jones ME. Kinetic studies of the transfer of esterified cholesterol between human plasma low and high density lipoproteins. J Lipid Res. 1980;21:238–249
  6. Ha YC, Barter PJ. Differences in plasma cholesterol ester transfer activity in sixteen vertebrate species. Comp Biochem Physiol B. 1982;71:265–269
  7. 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;273:5033–5036
  8. Rittershaus CW, Miller DP, Thomas LJ, Picard MD, Honan CM, Emmett CD, et al Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aortic lesions in a rabbit model of atherosclerosis. Arterioscler Thromb Vasc Biol. 2000;20:2106–2112
  9. Okamoto H, Yonemori F, Wakitani K, Minowa T, Maeda K, Shinkai H. A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature. 2000;406:203–207
  10. 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 NZW rabbits. J Lipid Res. 2007;48:1263–1272
  11. Yamashita S, Sprecher DL, Sakai N, Matsuzawa Y, Tarui S, Hui DY. Accumulation of apolipoprotein E-rich high density lipoproteins in hyperalphalipoproteinemic human subjects with deficiency of cholesteryl ester transfer protein. J Clin Invest. 1990;86:688–695
  12. Wang N, Lan D, Chen W, Matsuura F, Tall AR. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc Natl Acad Sci U S A. 2004;101:9774–9779
  13. Yvan-Charvet L, Matsuura F, Wang N, Bamberger MJ, Nguyen T, Rinninger F, et al. Inhibition of cholesteryl ester transfer protein by torcetrapib modestly increases macrophage cholesterol efflux to HDL. Arterioscler Thromb Vasc Biol. 2007;27:1132–1138
  14. Thompson A, Di Angelantonio E, Sarwar N, Erqou S, Saleheen D, Dullaart RP, et al. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA. 2008;299:2777–2788
  15. de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, de Graaf J, Zwinderman AH, Posma JL, 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
  16. Kastelein JJ, van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ, et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med. 2007;356:1620–1630
  17. Bots ML, Visseren FL, Evans GW, Riley WA, Revkin JH, Tegeler CH, et al. Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. Lancet. 2007;370:153–160
  18. 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;356:1304–1316
  19. Shear C, Beltangady M, Ports W, Duggan W, Barter P. Torcetrapib: predictors of increased clinical risk in the ILLUMINATE study. Circulation. 2008;118:S_370–S_371Abstract 1694
  20. Nicholls SJ, Tuzcu EM, Brennan DM, Tardif JC, Nissen SE. 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;118:2506–2514
  21. Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW, et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med. 2004;350:1505–1515
  22. Hu X, Dietz JD, Xia C, Knight DR, Loging WT, Smith AH, et al. Torcetrapib induces aldosterone and cortisol production by an intracellular calcium-mediated mechanism independently of cholesteryl ester transfer protein inhibition. Endocrinology. 2009;150:2211–2219
  23. Forrest MJ, Bloomfield D, Briscoe RJ, Brown PN, Cumiskey AM, Ehrhart J, 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;154:1465–1473
  24. Capponi AM, Clerc RG, Campos L, Perez A, Rincon Garriz JM, Maugeais C, et al. No increase in the in vitro production of aldosterone or the expression of CYP11B2 with the CETP modulator dalcetrapib (RO4607381/JTT-705), in contrast with torcetrapib. Circulation. 2008;118:S_452;Abstract 3618

 Statement of author disclosure: Please see the Author Disclosures section at the end of this article.

PII: S0002-9149(09)02375-3

doi: 10.1016/j.amjcard.2009.09.014

American Journal of Cardiology
Volume 104, Issue 10, Supplement , Pages 10E-15E , 16 November 2009

Article Tools

* Image Usage & Resolution