Virtual Histology Findings and Effects of Varying Doses of Atorvastatin Treatment

Summary

While statin treatment may induce plaque regression, the effect of statin on plaque composition with varying doses is unknown. This study assessed such effects by volumetric virtual histology intravascular ultrasound (VH-IVUS). In this prospective, randomized, double-blinded pilot study, statin-naïve patients with stable angina requiring percutaneous coronary intervention (PCI) were randomized to receive 6 months of either atorvastatin 10mg or 40 mg daily. VH-IVUS was performed in all non-PCI lesions at baseline and 6 months; all analyses were performed by core laboratory.

Timeline

Start

2007-08

Primary completion

2009-11

Completion

2010-06

Publications

• Background 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 May 16;285(19):2486-97. doi: 10.1001/jama.285.19.2486. No abstract available.
• Background De Backer G, Ambrosioni E, Borch-Johnsen K, Brotons C, Cifkova R, Dallongeville J, Ebrahim S, Faergeman O, Graham I, Mancia G, Manger Cats V, Orth-Gomer K, Perk J, Pyorala K, Rodicio JL, Sans S, Sansoy V, Sechtem U, Silber S, Thomsen T, Wood D; Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J. 2003 Sep;24(17):1601-10. doi: 10.1016/s0195-668x(03)00347-6. No abstract available.
• Background 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 Jul 6;360(9326):7-22. doi: 10.1016/S0140-6736(02)09327-3.
• Background Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004 Jul 13;110(2):227-39. doi: 10.1161/01.CIR.0000133317.49796.0E.
• Background Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR, Leslie S, Stern T; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001 Apr 4;285(13):1711-8. doi: 10.1001/jama.285.13.1711.
• Background Koren MJ, Hunninghake DB; ALLIANCE Investigators. Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the alliance study. J Am Coll Cardiol. 2004 Nov 2;44(9):1772-9. doi: 10.1016/j.jacc.2004.07.053.
• Background LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJ, Shepherd J, Wenger NK; Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005 Apr 7;352(14):1425-35. doi: 10.1056/NEJMoa050461. Epub 2005 Mar 8.
• Background Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495-504. doi: 10.1056/NEJMoa040583. Epub 2004 Mar 8.
• Background Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, Zhao XQ, Bisson BD, Fitzpatrick VF, Dodge HT. 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 Nov 8;323(19):1289-98. doi: 10.1056/NEJM199011083231901.
• Background Hausmann D, Erbel R, Alibelli-Chemarin MJ, Boksch W, Caracciolo E, Cohn JM, Culp SC, Daniel WG, De Scheerder I, DiMario C, et al. The safety of intracoronary ultrasound. A multicenter survey of 2207 examinations. Circulation. 1995 Feb 1;91(3):623-30. doi: 10.1161/01.cir.91.3.623.
• Background Potkin BN, Bartorelli AL, Gessert JM, Neville RF, Almagor Y, Roberts WC, Leon MB. Coronary artery imaging with intravascular high-frequency ultrasound. Circulation. 1990 May;81(5):1575-85. doi: 10.1161/01.cir.81.5.1575.
• Background Tobis JM, Mallery J, Mahon D, Lehmann K, Zalesky P, Griffith J, Gessert J, Moriuchi M, McRae M, Dwyer ML, et al. Intravascular ultrasound imaging of human coronary arteries in vivo. Analysis of tissue characterizations with comparison to in vitro histological specimens. Circulation. 1991 Mar;83(3):913-26. doi: 10.1161/01.cir.83.3.913.
• Background Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ, Pinto FJ, Rosenfield K, Siegel RJ, Tuzcu EM, Yock PG. American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2001 Apr;37(5):1478-92. doi: 10.1016/s0735-1097(01)01175-5. No abstract available.
• Background Mintz GS, Painter JA, Pichard AD, Kent KM, Satler LF, Popma JJ, Chuang YC, Bucher TA, Sokolowicz LE, Leon MB. Atherosclerosis in angiographically "normal" coronary artery reference segments: an intravascular ultrasound study with clinical correlations. J Am Coll Cardiol. 1995 Jun;25(7):1479-85. doi: 10.1016/0735-1097(95)00088-l.
• Background Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, Crowe T, Howard G, Cooper CJ, Brodie B, Grines CL, DeMaria AN; REVERSAL Investigators. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004 Mar 3;291(9):1071-80. doi: 10.1001/jama.291.9.1071.
• Background Nissen SE. Application of intravascular ultrasound to characterize coronary artery disease and assess the progression or regression of atherosclerosis. Am J Cardiol. 2002 Feb 21;89(4A):24B-31B. doi: 10.1016/s0002-9149(02)02217-8.
• Background Takagi T, Yoshida K, Akasaka T, Hozumi T, Morioka S, Yoshikawa J. Intravascular ultrasound analysis of reduction in progression of coronary narrowing by treatment with pravastatin. Am J Cardiol. 1997 Jun 15;79(12):1673-6. doi: 10.1016/s0002-9149(97)00221-x.
• Background Schartl M, Bocksch W, Koschyk DH, Voelker W, Karsch KR, Kreuzer J, Hausmann D, Beckmann S, Gross M. Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease. Circulation. 2001 Jul 24;104(4):387-92. doi: 10.1161/hc2901.093188.
• Background Jensen LO, Thayssen P, Pedersen KE, Stender S, Haghfelt T. Regression of coronary atherosclerosis by simvastatin: a serial intravascular ultrasound study. Circulation. 2004 Jul 20;110(3):265-70. doi: 10.1161/01.CIR.0000135215.75876.41. Epub 2004 Jul 6.
• Background Okazaki S, Yokoyama T, Miyauchi K, Shimada K, Kurata T, Sato H, Daida H. Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study. Circulation. 2004 Aug 31;110(9):1061-8. doi: 10.1161/01.CIR.0000140261.58966.A4. Epub 2004 Aug 23.
• Background Kimura BJ, Bhargava V, DeMaria AN. Value and limitations of intravascular ultrasound imaging in characterizing coronary atherosclerotic plaque. Am Heart J. 1995 Aug;130(2):386-96. doi: 10.1016/0002-8703(95)90457-3.
• Background Moore MP, Spencer T, Salter DM, Kearney PP, Shaw TR, Starkey IR, Fitzgerald PJ, Erbel R, Lange A, McDicken NW, Sutherland GR, Fox KA. Characterisation of coronary atherosclerotic morphology by spectral analysis of radiofrequency signal: in vitro intravascular ultrasound study with histological and radiological validation. Heart. 1998 May;79(5):459-67. doi: 10.1136/hrt.79.5.459.
• Background Watson RJ, McLean CC, Moore MP, Spencer T, Salter DM, Anderson T, Fox KA, McDicken WN. Classification of arterial plaque by spectral analysis of in vitro radio frequency intravascular ultrasound data. Ultrasound Med Biol. 2000 Jan;26(1):73-80. doi: 10.1016/s0301-5629(99)00112-x.
• Background Nair A, Kuban BD, Tuzcu EM, Schoenhagen P, Nissen SE, Vince DG. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation. 2002 Oct 22;106(17):2200-6. doi: 10.1161/01.cir.0000035654.18341.5e.
• Background Nasu K, Tsuchikane E, Katoh O, Vince DG, Virmani R, Surmely JF, Murata A, Takeda Y, Ito T, Ehara M, Matsubara T, Terashima M, Suzuki T. Accuracy of in vivo coronary plaque morphology assessment: a validation study of in vivo virtual histology compared with in vitro histopathology. J Am Coll Cardiol. 2006 Jun 20;47(12):2405-12. doi: 10.1016/j.jacc.2006.02.044. Epub 2006 May 30.
• Background Rodriguez-Granillo GA, Garcia-Garcia HM, Mc Fadden EP, Valgimigli M, Aoki J, de Feyter P, Serruys PW. In vivo intravascular ultrasound-derived thin-cap fibroatheroma detection using ultrasound radiofrequency data analysis. J Am Coll Cardiol. 2005 Dec 6;46(11):2038-42. doi: 10.1016/j.jacc.2005.07.064. Epub 2005 Nov 9.
• Background Kolodgie FD, Burke AP, Farb A, Gold HK, Yuan J, Narula J, Finn AV, Virmani R. The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr Opin Cardiol. 2001 Sep;16(5):285-92. doi: 10.1097/00001573-200109000-00006.
• Background Virmani R, Burke AP, Kolodgie FD, Farb A. Vulnerable plaque: the pathology of unstable coronary lesions. J Interv Cardiol. 2002 Dec;15(6):439-46. doi: 10.1111/j.1540-8183.2002.tb01087.x.
• Background Rioufol G, Finet G, Ginon I, Andre-Fouet X, Rossi R, Vialle E, Desjoyaux E, Convert G, Huret JF, Tabib A. Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study. Circulation. 2002 Aug 13;106(7):804-8. doi: 10.1161/01.cir.0000025609.13806.31.
• Background Rioufol G, Gilard M, Finet G, Ginon I, Boschat J, Andre-Fouet X. Evolution of spontaneous atherosclerotic plaque rupture with medical therapy: long-term follow-up with intravascular ultrasound. Circulation. 2004 Nov 2;110(18):2875-80. doi: 10.1161/01.CIR.0000146337.05073.22. Epub 2004 Oct 18.
• Background Steinberg D. Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: part II: the early evidence linking hypercholesterolemia to coronary disease in humans. J Lipid Res. 2005 Feb;46(2):179-90. doi: 10.1194/jlr.R400012-JLR200. Epub 2004 Nov 16.

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Indications