Clinical InvestigationPreventional and RehabilitationEffect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercholesterolemic patients: A high-resolution magnetic resonance imaging trial
Section snippets
Patient population
The randomized, double-blind ORION trial (4522IL/0044) was conducted at the University of Washington, Seattle, WA, and the University of Utah, Salt Lake City, Utah, from January 6, 2000 (first patient enrolled), through August 5, 2004 (last patient completed). The trial was designed and conducted in accordance with the Declaration of Helsinki and in compliance with the ethical principles of good clinical practice. Appropriate institutional review boards approved the trial, and all patients gave
Patient population
During the 2-year ORION trial, 4 of 43 subjects did not complete the study because of an adverse event (n = 2), withdrawn consent (n = 1), or other reasons (n = 1). Of the 39 patients who completed the study, all remained asymptomatic and 33 (nlow = 13, nhigh = 20) (Table I) had matched baseline and 2-year scans of sufficient image quality for identification of the vessel boundaries and automated compositional analysis.
Laboratory outcomes
After 2 years of rosuvastatin therapy, there was a significant reduction in
Discussion
The findings presented herein represent the first prospective, long-term MRI study on the in vivo effects of statin therapy on carotid plaque composition. In a small asymptomatic population, we found a significant reduction in the proportion of the plaque composed of the LRNC and a significant increase in fibrous tissue over the course of 2 years of treatment with rosuvastatin. In addition, in subjects without imaging evidence of an LRNC at baseline, none developed an LRNC during the 2 years of
Acknowledgment
We gratefully acknowledge the patients who participated in this trial. In addition, we wish to thank Beverly Hashimoto, MD, Amber Harms, Monica Smith, Joe Davis, Darlene Pulley, Elizabeth Ellington, Bridget Mraz, and Molly Zaccardi for their involvement with recruitment and data collection, and Joe Hirsch of BioScience Communications and Karen McFadden and Gregg Truitt of AstraZeneca for their editorial and technical assistance in the preparation of the manuscript.
References (26)
- et al.
Predictors of carotid atherosclerotic plaque progression as measured by noninvasive magnetic resonance imaging
Atherosclerosis
(2007) - et al.
Effects of aggressive versus conventional lipid-lowering therapy by simvastatin on human atherosclerotic lesions: a prospective, randomized, double-blind trial with high-resolution magnetic resonance imaging
J Am Coll Cardiol
(2005) - et al.
Guidelines for carotid endarterectomy. A multidisciplinary consensus statement from the Ad Hoc Committee, American Heart Association
Circulation
(1995) - et al.
Trends and strategies for myocardial revascularization
Thorac Cardiovasc Surg
(1996) - et al.
Coronary plaque disruption
Circulation
(1995) - et al.
Vulnerable plaque: the pathology of unstable coronary lesions
J Interv Cardiol
(2002) - et al.
Magnetic resonance images lipid, fibrous, calcified, hemorrhagic, and thrombotic components of human atherosclerosis in vivo
Circulation
(1996) - et al.
Quantitative evaluation of carotid plaque composition by in vivo MRI
Arterioscler Thromb Vasc Biol
(2005) - et al.
Automated in vivo segmentation of carotid plaque MRI with morphology-enhanced probability maps
Magn Reson Med
(2006) - et al.
Sample size calculation for clinical trials using magnetic resonance imaging for the quantitative assessment of carotid atherosclerosis
J Cardiovasc Magn Reson
(2005)
Presence of intraplaque hemorrhage stimulates progression of carotid atherosclerotic plaques: a high-resolution magnetic resonance imaging study
Circulation
Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: two years' follow-up by high-resolution noninvasive magnetic resonance imaging
Circulation
Statin-induced cholesterol lowering and plaque regression after 6 months of magnetic resonance imaging–monitored therapy
Circulation
Cited by (240)
Intracranial Atherosclerotic Plaque as a Potential Cause of Embolic Stroke of Undetermined Source
2021, Journal of the American College of CardiologyCarotid Artery Disease
2021, Stroke: Pathophysiology, Diagnosis, and ManagementBiomarkers
2021, Principles of Translational Science in Medicine: From Bench to Bedside, Third EditionAssociation of Plasma Marker of Oxidized Lipid with Histologic Plaque Instability in Patients with Peripheral Artery Disease
2020, Annals of Vascular SurgeryLocal and systemic factors associated with quantitative stiffness of carotid plaque
2024, Acta Neurochirurgica
This research was supported by AstraZeneca, London, Unted Kingdom, and the National Institutes of Health, Bethesda, MD (T-32, HL07838).