Effect of Statin Treatment on Modifying Plaque Composition: A Double-Blind, Randomized Study.

Abstract

How statins alter the natural course of coronary atherosclerosis with compositional changes remains unclear. This study aimed to determine the effect of statin therapy on modifying plaque composition. The STABLE (Statin and Atheroma Vulnerability Evaluation) prospective, single-center, double-blind, randomized study evaluated the effect of statins on functionally insignificant coronary stenoses. We randomly assigned 312 patients with a virtual histology (VH) intravascular ultrasound-defined fibroatheroma-containing index lesion to rosuvastatin 40 mg versus 10 mg (2:1 ratio). In 225 (72%) patients, grayscale- and VH-intravascular ultrasound were completed at baseline and 12 months. The primary endpoint was the change in VH-defined percent compositional volume within the target segment from baseline to follow-up in the per-protocol analysis set. Percent necrotic core (NC) volume within the target segment significantly decreased from 21.3 ± 6.8% to 18.0 ± 7.5% during 1-year follow-up, whereas the percent fibrofatty volume increased (11.7 ± 5.8% vs. 14.8 ± 9.3%; all p < 0.001). Percent fibrous (59.4 ± 7.8% vs. 59.2 ± 8.6%) and dense calcium (7.6 ± 5.1% vs. 7.8 ± 5.6%) volumes were unchanged. Frequencies of VH (55% vs. 29%) decreased significantly. Normalized total (202.9 ± 72.3 mm(3) vs. 188.5 ± 67.8 mm(3); p = 0.001) and percent (51.4 ± 8.3% vs. 50.4 ± 8.8%; p = 0.018) atheroma volumes decreased. Independent predictors of percent NC volume change were body mass index (β = 0.37; 95% confidence interval [CI]: 0.05 to 0.70), high sensitivity C-reactive protein (β = -3.16; 95% CI: -5.64 to -0.69), and baseline percent NC volume (β = -0.44; 95% CI: -0.68 to -0.19; all p < 0.05). VH-defined percent compositional volume changes in the rosuvastatin 40- and 10-mg groups were similar. Rosuvastatin reduced NC and plaque volume and decreased thin-cap fibroatheroma rate. There were no significant differences between high- versus moderate-intensity rosuvastatin. (Statin and Atheroma Vulnerability Evaluation [STABLE]; NCT00997880).