Circulation, Vol 89, 959-968, Copyright © 1994 by American Heart Association
D Waters, L Higginson, P Gladstone, B Kimball, M Le May, SJ Boccuzzi and J Lesperance
BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are
widely prescribed for hyperlipidemia, yet their effect on the evolution of
coronary atherosclerosis has not been defined. METHODS AND RESULTS: To
address this issue, 331 patients with diffuse but not necessarily severe
coronary atherosclerosis documented on a recent arteriogram and with
fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a
randomized, double-blind, placebo-controlled trial. All patients received
intensive dietary counseling. Lovastatin or placebo was begun at 20 mg/d
and was titrated to 40 and 80 mg during the first 16 weeks to attain a
fasting low-density lipoprotein (LDL) cholesterol < or = 130 mg/dL. The
mean lovastatin dose was 36 mg/d. Coronary arteriography was repeated after
2 years. In 299 patients (90%), 3858 coronary segments containing 2309
stenoses were measured blindly on pairs of films with an automated
computerized quantitative system. Total and LDL cholesterol decreased by 21
+/- 11% and 29 +/- 11%, respectively, in the lovastatin-treated group but
changed by < 2% in placebo patients. The primary end point, coronary
change score, defined as the per-patient mean of the minimum lumen diameter
changes (follow-up minus baseline angiogram) for all lesions measured,
excluding those < 25% on both films, worsened by 0.09 +/- 0.16 mm in the
placebo group and by 0.05 +/- 0.13 mm in the lovastatin group (P = .01).
Progression (a worsening in minimum diameter of one or more stenoses by
> or = 0.4 mm) with no regression at other sites occurred in 48 of 146
lovastatin and 76 of 153 placebo patients (33% versus 50%, P = .003). New
coronary lesions developed in 23 lovastatin and 49 placebo patients (P =
.001). The beneficial effect of treatment was most pronounced in the more
numerous, milder lesions and in patients whose baseline total or LDL
cholesterol levels were above the group median. CONCLUSIONS: Lovastatin
slows the progression of coronary atherosclerosis and inhibits the
development of new coronary lesions.
ARTICLES
Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography. The Canadian Coronary Atherosclerosis Intervention Trial
Division of Cardiology, Hartford Hospital, Conn 06115.
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T. A. Pearson and M. Myerson Treatment of Hypercholesterolemia in Women: Equality, Effectiveness, and Extrapolation of Evidence JAMA, April 23, 1997; 277(16): 1320 - 1321. [Abstract] [PDF]
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S. Colli, S. Eligini, M. Lalli, M. Camera, R. Paoletti, and E. Tremoli Vastatins Inhibit Tissue Factor in Cultured Human Macrophages: A Novel Mechanism of Protection Against Atherothrombosis Arterioscler Thromb Vasc Biol, February 1, 1997; 17(2): 265 - 272. [Abstract] [Full Text]
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The Post Coronary Artery Bypass Graft Trial Invest The Effect of Aggressive Lowering of Low-Density Lipoprotein Cholesterol Levels and Low-Dose Anticoagulation on Obstructive Changes in Saphenous-Vein Coronary-Artery Bypass Grafts N. Engl. J. Med., January 16, 1997; 336(3): 153 - 163. [Abstract] [Full Text] [PDF]
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A. Lucas, L.-y. Liu, J. Macen, P. Nash, E. Dai, M. Stewart, K. Graham, W. Etches, L. Boshkov, P. N. Nation, et al. Virus-Encoded Serine Proteinase Inhibitor SERP-1 Inhibits Atherosclerotic Plaque Development After Balloon Angioplasty Circulation, December 1, 1996; 94(11): 2890 - 2900. [Abstract] [Full Text]
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B. D. Miller, E. L. Alderman, W. L. Haskell, J. M. Fair, and R. M. Krauss Predominance of Dense Low-Density Lipoprotein Particles Predicts Angiographic Benefit of Therapy in the Stanford Coronary Risk Intervention Project Circulation, November 1, 1996; 94(9): 2146 - 2153. [Abstract] [Full Text]
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D. Waters, J. Lesperance, P. Gladstone, S. J. Boccuzzi, T. Cook, R. Hudgin, G. Krip, and L. Higginson Effects of Cigarette Smoking on the Angiographic Evolution of Coronary Atherosclerosis: A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) Substudy Circulation, August 15, 1996; 94(4): 614 - 621. [Abstract] [Full Text]
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J. Wouter Jukema, A. J. van Boven, A. H. Zwinderman, E. T. Bal, J. H. C. Reiber, and A. V. G. Bruschke The Influence of Angiographic Endpoints on the Outcome of Lipid Intervention Studies: A Proposal for Standardization Angiology, July 1, 1996; 47(7): 633 - 642. [Abstract] [PDF]
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R. S. Rosenson Beyond Low-Density Lipoprotein Cholesterol: A Perspective on Low High-Density Lipoprotein Disorders and Lp(a) Lipoprotein Excess Arch Intern Med, June 24, 1996; 156(12): 1278 - 1284. [Abstract] [PDF]
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R. Marchioli, R. M. Marfisi, F. Carinci, and G. Tognoni Meta-analysis, Clinical Trials, and Transferability of Research Results Into Practice: The Case of Cholesterol-Lowering Interventions in the Secondary Prevention of Coronary Heart Disease Arch Intern Med, June 10, 1996; 156(11): 1158 - 1172. [Abstract] [PDF]
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A. A. Kroon, W. R.M. Aengevaeren, T. van der Werf, G. J.H. Uijen, J. H.C. Reiber, A. V.G. Bruschke, and A. F.H. Stalenhoef LDL-Apheresis Atherosclerosis Regression Study (LAARS) : Effect of Aggressive Versus Conventional Lipid Lowering Treatment on Coronary Atherosclerosis Circulation, May 15, 1996; 93(10): 1826 - 1835. [Abstract] [Full Text]
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J. W. Jukema, A. H. Zwinderman, A. J. van Boven, J. H.C. Reiber, A. Van der Laarse, K. I. Lie, and A. V.G. Bruschke Evidence for a Synergistic Effect of Calcium Channel Blockers With Lipid-Lowering Therapy in Retarding Progression of Coronary Atherosclerosis in Symptomatic Patients With Normal to Moderately Raised Cholesterol Levels Arterioscler Thromb Vasc Biol, March 1, 1996; 16(3): 425 - 430. [Abstract] [Full Text]
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 D.R. Illingworth, E.A. Stein, R.H. Knopp, D.B. Hunninghake, M.H. Davidson, C.A. Dujovne, V.T. Miller, J.A. Tobert, P.M. Laskarzewski, J.L. Isaacsohn, et al. A Randomized Multicenter Trial Comparing the Efficacy of Simvastatin and Fluvastatin Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1996; 1(1): 23 - 29. [Abstract] [PDF]
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S. P. Azen, W. J. Mack, L. Cashin-Hemphill, L. LaBree, A. M. Shircore, R. H. Selzer, D. H. Blankenhorn, and H. N. Hodis Progression of Coronary Artery Disease Predicts Clinical Coronary Events : Long-term Follow-up From the Cholesterol Lowering Atherosclerosis Study Circulation, January 1, 1996; 93(1): 34 - 41. [Abstract] [Full Text]
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L. Lacoste, J. Y.T. Lam, J. Hung, G. Letchacovski, C. B. Solymoss, and D. Waters Hyperlipidemia and Coronary Disease : Correction of the Increased Thrombogenic Potential With Cholesterol Reduction Circulation, December 1, 1995; 92(11): 3172 - 3177. [Abstract] [Full Text]
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D. Waters, L. Higginson, P. Gladstone, S. J. Boccuzzi, T. Cook, and J. Lesperance Effects of Cholesterol Lowering on the Progression of Coronary Atherosclerosis in Women : A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) Substudy Circulation, November 1, 1995; 92(9): 2404 - 2410. [Abstract] [Full Text]
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Y. Ozaki, D. Keane, and P. W. Serruys Progression and Regression of Coronary Stenosis in the Long-term Follow-up of Vasospastic Angina Circulation, November 1, 1995; 92(9): 2446 - 2456. [Abstract] [Full Text]
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K. L. Gould, D. Ornish, L. Scherwitz, S. Brown, R. P. Edens, M. J. Hess, N. Mullani, L. Bolomey, F. Dobbs, W. T. Armstrong, et al. Changes in Myocardial Perfusion Abnormalities by Positron Emission Tomography After Long-term, Intense Risk Factor Modification JAMA, September 20, 1995; 274(11): 894 - 901. [Abstract] [PDF]
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A. M. Gotto Jr Lipid Lowering, Regression, and Coronary Events : A Review of the Interdisciplinary Council on Lipids and Cardiovascular Risk Intervention, Seventh Council Meeting Circulation, August 1, 1995; 92(3): 646 - 656. [Full Text]
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R. J. Havel and E. Rapaport Management of Primary Hyperlipidemia N. Engl. J. Med., June 1, 1995; 332(22): 1491 - 1498. [Full Text] [PDF]
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 M. Oliver, P. Poole-Wilson, J. Shepherd, and M. J Tikkanen Lower patients' cholesterol now BMJ, May 20, 1995; 310(6990): 1280 - 1281. [Full Text]
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J. W. Jukema, A. V.G. Bruschke, A. J. van Boven, J. H.C. Reiber, E. T. Bal, A. H. Zwinderman, H. Jansen, G. J.M. Boerma, F. M. van Rappard, and K. I. Lie Effects of Lipid Lowering by Pravastatin on Progression and Regression of Coronary Artery Disease in Symptomatic Men With Normal to Moderately Elevated Serum Cholesterol Levels : The Regression Growth Evaluation Statin Study (REGRESS) Circulation, May 15, 1995; 91(10): 2528 - 2540. [Abstract] [Full Text]
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P. Theroux Angiographic and Clinical Progression in Unstable Angina : From Clinical Observations to Clinical Trials Circulation, May 1, 1995; 91(9): 2295 - 2298. [Full Text]
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G. N. Levine, J. F. Keaney, and J. A. Vita Cholesterol Reduction in Cardiovascular Disease -- Clinical Benefits and Possible Mechanisms N. Engl. J. Med., February 23, 1995; 332(8): 512 - 521. [Full Text] [PDF]
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W. S. Weintraub, S. J. Boccuzzi, J. L. Klein, A. S. Kosinski, S. B. King, R. Ivanhoe, J. C. Cedarholm, M. E. Stillabower, J. D. Talley, S. J. DeMaio, et al. Lack of Effect of Lovastatin on Restenosis after Coronary Angioplasty N. Engl. J. Med., November 17, 1994; 331(20): 1331 - 1337. [Abstract] [Full Text]
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 SLOWING CORONARY DISEASE WITH LOVASTATIN Journal Watch (General), April 12, 1994; 1994(412): 6 - 6. [Full Text]
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