Circulation, Vol 90, 1679-1687, Copyright © 1994 by American Heart Association
CD Furberg, HP Adams Jr, WB Applegate, RP Byington, MA Espeland, T Hartwell, DB Hunninghake, DS Lefkowitz, J Probstfield and WA Riley
BACKGROUND: HMG CoA reductase inhibitors (or statins), a new class of
lipid-lowering compounds, have raised expectations for more widespread use
than that of the older lipid-lowering drugs. Not only are they more
effective in lowering LDL cholesterol, but they are better tolerated as
well. No data exist concerning the effect of statins on early carotid
atherosclerosis and clinical events in men and women who have moderately
elevated LDL cholesterol levels but are free of symptomatic cardiovascular
disease. METHODS AND RESULTS: Lovastatin (20 to 40 mg/d) or its placebo was
evaluated in a double-blind, randomized clinical trial with factorial
design along with warfarin (1 mg/d) or its placebo. This report is limited
to the lovastatin component of the trial. Daily aspirin (81 mg/d) was
recommended for everyone. Enrollment included 919 asymptomatic men and
women, 40 to 79 years old, with early carotid atherosclerosis as defined by
B-mode ultrasonography and LDL cholesterol between the 60th and 90th
percentiles. The 3-year change in mean maximum intimal-medial thickness
(IMT) in 12 walls of the carotid arteries was the primary outcome; change
in single maximum IMT and incidence of major cardiovascular events were
secondary outcomes. LDL cholesterol fell 28%, from 156.6 mg/dL at baseline
to 113.1 mg/dL at 6 months (P < .0001), in the lovastatin groups and was
largely unchanged in the lovastatin-placebo groups. Among participants not
on warfarin, regression of the mean maximum IMT was seen after 12 months in
the lovastatin group compared with the placebo group; the 3-year difference
was statistically significant (P = .001). A larger favorable effect of
lovastatin was observed for the change in single maximum IMT but was not
statistically significant (P = .12). Five lovastatin-treated participants
suffered major cardiovascular events--coronary heart disease mortality,
nonfatal myocardial infarction, or stroke--versus 14 in the
lovastatin-placebo groups (P = .04). One lovastatin-treated participant
died, compared with eight on lovastatin-placebo (P = .02). CONCLUSIONS: In
men and women with moderately elevated LDL cholesterol, lovastatin reverses
progression of IMT in the carotid arteries and appears to reduce the risk
of major cardiovascular events and mortality. Results from ongoing
large-scale clinical trials may further establish the clinical benefit of
statins.
ARTICLES
Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group
Department of Public Health Sciences, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1063.
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N. Koren-Morag, D. Tanne, E. Graff, U. Goldbourt, and for the Bezafibrate Infarction Prevention Study Gr Low- and High-Density Lipoprotein Cholesterol and Ischemic Cerebrovascular Disease: The Bezafibrate Infarction Prevention Registry Arch Intern Med, May 13, 2002; 162(9): 993 - 999. [Abstract] [Full Text] [PDF]
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R. F. Redberg, P. Greenland, V. Fuster, K. Pyorala, S. N. Blair, A. R. Folsom, A. B. Newman, D. H. O'Leary, T. J. Orchard, B. Psaty, et al. Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group III: Risk Assessment in Persons With Diabetes Circulation, May 7, 2002; 105 (18): e144 - e152. [Full Text] [PDF]
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O. Wiklund, J. Hulthe, J. Wikstrand, C. Schmidt, S.-O. Olofsson, and G. Bondjers Effect of Controlled Release/Extended Release Metoprolol on Carotid Intima-Media Thickness in Patients With Hypercholesterolemia: A 3-Year Randomized Study Stroke, February 1, 2002; 33(2): 572 - 577. [Abstract] [Full Text] [PDF]
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R. L. Sacco Extracranial Carotid Stenosis N. Engl. J. Med., October 11, 2001; 345(15): 1113 - 1118. [Full Text] [PDF]
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P. Rubba, S. Panico, M. G. Bond, G. Covetti, E. Celentano, A. Iannuzzi, R. Galasso, M. A. Belisario, A. Pastinese, L. Sacchetti, et al. Site-Specific Atherosclerotic Plaques in the Carotid Arteries of Middle-Aged Women From Southern Italy: Associations With Traditional Risk Factors and Oxidation Markers Stroke, September 1, 2001; 32(9): 1953 - 1959. [Abstract] [Full Text] [PDF]
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P. Amarenco Hypercholesterolemia, lipid-lowering agents, and the risk for brain infarction Neurology, September 1, 2001; 57(90002): S35 - 44. [Abstract] [Full Text]
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B. Hedblad, J. Wikstrand, L. Janzon, H. Wedel, and G. Berglund Low-Dose Metoprolol CR/XL and Fluvastatin Slow Progression of Carotid Intima-Media Thickness : Main Results From the {beta}-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS) Circulation, April 3, 2001; 103(13): 1721 - 1726. [Abstract] [Full Text] [PDF]
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S. Bandyopadhyay, A.J. Bayer, and M.S. O'Mahony Age and gender bias in statin trials QJM, March 1, 2001; 94(3): 127 - 132. [Abstract] [Full Text] [PDF]
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W. S. Aronow Treatment of Older Persons With Hypercholesterolemia With and Without Cardiovascular Disease J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2001; 56(3): 138M - 145. [Abstract] [Full Text]
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T. J. Tegos, E. Kalodiki, M. M. Sabetai, and A. N. Nicolaides The Genesis of Atherosclerosis and Risk Factors: A Review Angiology, February 1, 2001; 52(2): 89 - 98. [Abstract] [PDF]
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L. B. Goldstein, R. Adams, K. Becker, C. D. Furberg, P. B. Gorelick, G. Hademenos, M. Hill, G. Howard, V. J. Howard, B. Jacobs, et al. Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association Circulation, January 2, 2001; 103(1): 163 - 182. [Full Text] [PDF]
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C. Held, P. Hjemdahl, S.V. Eriksson, I. Bjorkander, L. Forslund, and N. Rehnqvist Prognostic implications of intima-media thickness and plaques in the carotid and femoral arteries in patients with stable angina pectoris Eur. Heart J., January 1, 2001; 22(1): 62 - 72. [Abstract] [PDF]
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L. B. Goldstein, R. Adams, K. Becker, C. D. Furberg, P. B. Gorelick, G. Hademenos, M. Hill, G. Howard, V. J. Howard, B. Jacobs, et al. Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association Stroke, January 1, 2001; 32(1): 280 - 299. [Full Text] [PDF]
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M. Rubenfire, S. Rajagopalan, and L. Mosca Carotid artery vasoreactivity in response to sympathetic stress correlates with coronary disease risk and is independent of wall thickness J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2192 - 2197. [Abstract] [Full Text] [PDF]
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J. Hsia, J. A. Simon, F. Lin, W. B. Applegate, M. T. Vogt, D. Hunninghake, and M. Carr Peripheral Arterial Disease in Randomized Trial of Estrogen With Progestin in Women With Coronary Heart Disease : The Heart and Estrogen/Progestin Replacement Study Circulation, October 31, 2000; 102(18): 2228 - 2232. [Abstract] [Full Text] [PDF]
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M. Pignone, C. Phillips, and C. Mulrow Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised trials BMJ, October 21, 2000; 321(7267): 983 - 986. [Abstract] [Full Text]
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B. Pitt, R. P. Byington, C. D. Furberg, D. B. Hunninghake, G. B. J. Mancini, M. E. Miller, and W. Riley Effect of Amlodipine on the Progression of Atherosclerosis and the Occurrence of Clinical Events Circulation, September 26, 2000; 102(13): 1503 - 1510. [Abstract] [Full Text] [PDF]
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H. D. White, R. J. Simes, N. E. Anderson, G. J. Hankey, J. D.G. Watson, D. Hunt, D. M. Colquhoun, P. Glasziou, S. MacMahon, A. C. Kirby, et al. Pravastatin Therapy and the Risk of Stroke N. Engl. J. Med., August 3, 2000; 343(5): 317 - 326. [Abstract] [Full Text] [PDF]
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P. Sun, K. M. Dwyer, C. N. B. Merz, W. Sun, C. A. Johnson, A. M. Shircore, and J. H. Dwyer Blood Pressure, LDL Cholesterol, and Intima-Media Thickness : A Test of the "Response to Injury" Hypothesis of Atherosclerosis Arterioscler Thromb Vasc Biol, August 1, 2000; 20(8): 2005 - 2010. [Abstract] [Full Text] [PDF]
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D. Baldassarre, E. Tremoli, M. Amato, F. Veglia, A. Bondioli, and C. R. Sirtori Reproducibility Validation Study Comparing Analog and Digital Imaging Technologies for the Measurement of Intima-Media Thickness Stroke, May 1, 2000; 31(5): 1104 - 1110. [Abstract] [Full Text] [PDF]
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A. Castillo-Richmond, R. H. Schneider, C. N. Alexander, R. Cook, H. Myers, S. Nidich, C. Haney, M. Rainforth, and J. Salerno Effects of Stress Reduction on Carotid Atherosclerosis in Hypertensive African Americans Stroke, March 1, 2000; 31(3): 568 - 573. [Abstract] [Full Text] [PDF]
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D. C. Hess, A. M. Demchuk, L. M. Brass, and F. M. Yatsu HMG-CoA reductase inhibitors (statins): A promising approach to stroke prevention Neurology, February 22, 2000; 54(4): 790 - 796. [Abstract] [Full Text] [PDF]
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P. Greenland, J. Abrams, G. P. Aurigemma, M. G. Bond, L. T. Clark, M. H. Criqui, J. R. Crouse III, L. Friedman, V. Fuster, D. M. Herrington, et al. Prevention Conference V : Beyond Secondary Prevention : Identifying the High-Risk Patient for Primary Prevention : Noninvasive Tests of Atherosclerotic Burden : Writing Group III Circulation, January 4, 2000; 101 (1): e16 - e22. [Full Text] [PDF]
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C. J. Vaughan, A. M. Gotto Jr., and C. T. Basson The evolving role of statins in the management of atherosclerosis J. Am. Coll. Cardiol., January 1, 2000; 35(1): 1 - 10. [Abstract] [Full Text] [PDF]
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J. C. LaRosa, J. He, and S. Vupputuri Effect of Statins on Risk of Coronary Disease: A Meta-analysis of Randomized Controlled Trials JAMA, December 22, 1999; 282(24): 2340 - 2346. [Abstract] [Full Text] [PDF]
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Discontinuation of Growth Hormone (GH) Treatment: Metabolic Effects in GH-Deficient and GH-Sufficient Adolescent Patients Compared with Control Subjects J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4516 - 4524. [Abstract] [Full Text]
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E. R Mohler III, N. Delanty, D. J Rader, and E. C Raps Statins and cerebrovascular disease: plaque attack to prevent brain attack Vascular Medicine, November 1, 1999; 4(4): 269 - 272. [Abstract] [PDF]
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M. Hashimoto, M. Eto, M. Akishita, K. Kozaki, J. Ako, K. Iijima, S. Kim, K. Toba, M. Yoshizumi, and Y. Ouchi Correlation Between Flow-Mediated Vasodilatation of the Brachial Artery and Intima-Media Thickness in the Carotid Artery in Men Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2795 - 2800. [Abstract] [Full Text] [PDF]
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G. W. Albers, R. G. Hart, H. L. Lutsep, D. W. Newell, and R. L. Sacco Supplement to the Guidelines for the Management of Transient Ischemic Attacks : A Statement From the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks, Stroke Council, American Heart Association Stroke, November 1, 1999; 30(11): 2502 - 2511. [Full Text] [PDF]
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