Elsevier

American Heart Journal

Volume 155, Issue 3, March 2008, Pages 584.e1-584.e8
American Heart Journal

Clinical Investigation
Preventional and Rehabilitation
Effect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercholesterolemic patients: A high-resolution magnetic resonance imaging trial

https://doi.org/10.1016/j.ahj.2007.11.018Get rights and content

Background

Magnetic resonance imaging (MRI) can noninvasively assess changes in atherosclerotic plaque morphology and composition. The ORION trial assessed the effects of rosuvastatin on carotid plaque volume and composition.

Methods

The randomized, double-blind ORION trial used 1.5-T MRI to image carotid atherosclerotic plaques at baseline and after 24 months of treatment. Forty-three patients with fasting low-density lipoprotein cholesterol ≥100 and <250 mg/dL and 16% to 79% carotid stenosis by duplex ultrasound were randomized to receive either a low (5 mg) or high (40/80 mg) dose of rosuvastatin.

Results

After 24 months, 33 patients had matched serial MRI scans to compare by reviewers blinded to clinical data, dosage, and temporal sequence of scans. Low-density lipoprotein cholesterol was significantly reduced from baseline in both the low- and high-dose groups (38.2% and 59.9%, respectively, both P < .001). At 24 months, there were no significant changes in carotid plaque volume for either dosage group. In all patients with a lipid-rich necrotic core (LRNC) at baseline, the mean proportion of the vessel wall composed of LRNC (%LRNC) decreased by 41.4% (P = .005).

Conclusions

In patients with moderate hypercholesterolemia, both low- and high-dose rosuvastatin were effective in reducing low-density lipoprotein cholesterol. Furthermore, rosuvastatin was associated with a reduction in %LRNC, whereas the overall plaque burden remained unchanged over the course of 2 years of treatment. These findings provide evidence that statin therapy may have a beneficial effect on plaque volume and composition, as assessed by noninvasive MRI.

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.

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    This research was supported by AstraZeneca, London, Unted Kingdom, and the National Institutes of Health, Bethesda, MD (T-32, HL07838).

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