Abstract 1912: Time Course of Change in Plaque Composition Associated with Rosuvastatin Therapy as Assessed by High-Resolution Magnetic Resonance Imaging
Background: MRI studies of the natural history of carotid atherosclerosis show a slow but significant progression in mean vessel wall area (2.2%/yr; p<.005) and lipid-rich necrotic core (LRNC) size (10.9%/yr; p<.05). MRI showed that 2 yrs of intensive LDL-lowering with rosuvastatin (RSV) is associated with significant decrease in % of plaque composed of LRNC. The aim of this study is to assess the time course of change in overall morphology and composition of human carotid atherosclerosis associated with RSV therapy.
Methods: The randomized, double-blind ORION trial used 1.5T MRI to image carotid atherosclerotic plaques at baseline and after 6, 12, and 24 mos of RSV therapy. Forty-three patients with fasting LDL-C ≥100 and <250 mg/dL and 16%–79% carotid stenosis by duplex ultrasound received either low (5 mg) or high (40/80 mg) dose RSV. Area of lumen, wall, LRNC, and calcification were outlined by reviewers blinded to clinical data, dosage, and temporal sequence of scans. Cross-sectional images were matched for each time point using common carotid bifurcation as a fiducial marker. Compositional features are expressed as % of wall area (%LRNC = LRNC area/wall area*100).
Results: Thirty-nine subjects completed the study. The number of MRIs at each time point of sufficient quality for comparison with baseline was 33 at 6 mos, 37 at 12 mos, and 33 at 2 yrs. Significant reduction in LDL-C was seen in both low and high dose groups by 6 mos (37.8% and 62.1%, respectively; p<.001) and maintained throughout the study. No significant increase or decrease in mean lumen area, wall area, or % calcification was observed at any of the 4 time points. No subject without LRNC at baseline developed LRNC. Of 21 subjects with LRNC at enrollment, no significant change in %LRNC was observed at 6 and 12 mos compared with baseline, followed by a significant decrease at 24 mos in both low and high dose groups (41.4%, p=.005 vs baseline; p = NS between dose groups).
Conclusions: These results show that the observed reduction in proportion of plaque composed of LRNC was an effect of long-term (>1 yr) RSV therapy. This finding is consistent with time necessary for remodeling of a chronic disease process and indicates the importance of allowing adequate duration of observation in future clinical trial designs.