(Circulation. 2001;103:1721.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Low-Dose Metoprolol CR/XL and Fluvastatin Slow Progression of Carotid Intima-Media Thickness
Main Results From the ß-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS)
From the Department of Medicine (B.H., G.B.) and the Department of Community Medicine (B.H., L.J.), Malmö University Hospital, Lund University, Lund, Sweden; Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital (J.W.), Gothenburg, Sweden; and Nordic School of Public Health (H.W.), Gothenburg, Sweden. Dr Wikstrand is also senior medical advisor at Clinical Science, AstraZeneca, Mölndal, Sweden.
Correspondence to Professor Göran Berglund, Department of Medicine, Malmö University Hospital, S 205 02 Malmö, Sweden. E-mail Goran.Berglund{at}medforsk.mas.lu.se
Background—Statins reduce cardiovascular events and progression of carotid intima-media thickness (IMT). ß-Blockers are also known to reduce cardiovascular events, but less is known about their effects on carotid IMT.
Methods and Results—We conducted a randomized, double-blind, placebo-controlled, single-center trial to compare the effects of low-dose metoprolol CR/XL (25 mg once daily) and fluvastatin (40 mg once daily) on the progression of carotid IMT during 36 months of treatment in 793 subjects who had carotid plaque but no symptoms of carotid artery disease. Changes in mean IMT in the common carotid artery and maximal IMT in the bulb were the main outcome variables. Death and cardiovascular events were monitored. Progression of IMTmax in the carotid bulb at both 18 and 36 months was reduced by metoprolol CR/XL (-0.058 mm/y; 95% CI, -0.094 to -0.023; P=0.004; and -0.023 mm/y; 95% CI, -0.044 to -0.003; P=0.014, respectively). Incidence of cardiovascular events tended to be lower in metoprolol CR/XL–treated patients (5 versus 13 patients, P=0.055). Rate of IMTmean progression in the common carotid at 36 months was reduced by fluvastatin (-0.009 mm/y; 95% CI, -0.015 to -0.003; P=0.002). Women in the fluvastatin group had increased frequency of transiently high liver enzymes.
Conclusions—This is the first randomized trial to show that a ß-blocker can reduce the rate of progression of carotid IMT in clinically healthy, symptom-free subjects with carotid plaque. This suggests that ß-blockers may have a favorable effect on atherosclerosis development.
Key Words: drugs • ultrasonics • carotid arteries • trials
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|
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|
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|
|
|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 J. E Macioch, C D. Katsamakis, J. Robin, P. R Liebson, P. M Meyer, C. Geohas, J. S Raichlen, M. H Davidson, and S. B Feinstein Effect of contrast enhancement on measurement of carotid artery intimal medial thickness Vascular Medicine, February 1, 2004; 9(1): 7 - 12. [Abstract] [PDF]
|
|
|
|
|
|
P. Poredos Intima-media thickness: indicator of cardiovascular risk and measure of the extent of atherosclerosis Vascular Medicine, February 1, 2004; 9(1): 46 - 54. [Abstract] [PDF]
|
|
|
|
|
|
M. L. Bots, G. W. Evans, W. A. Riley, and D. E. Grobbee Carotid Intima-Media Thickness Measurements in Intervention Studies: Design Options, Progression Rates, and Sample Size Considerations: A Point of View Stroke, December 1, 2003; 34(12): 2985 - 2994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 B. M. Curtis and J. H. O'Keefe Jr Autonomic Tone as a Cardiovascular Risk Factor: The Dangers of Chronic Fight or Flight Mayo Clin. Proc., January 1, 2002; 77(1): 45 - 54. [Abstract] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|