Effect of Statin Treatment on Modifying Plaque Composition

Study Questions:

What is the effect of statin therapy on modifying plaque composition, and is there a dose-efficacy relationship?

Methods:

The STABLE (Statin and Atheroma Vulnerability Evaluation) prospective, single-center, double-blind, randomized study evaluated the effect of statins on functionally insignificant coronary stenosis (diameter stenosis 20-50%, >50% without perfusion defect on thallium scan or fractional flow reserve ≥0.8). A total of 312 patients with a virtual histology (VH) of intravascular ultrasound (IVUS)-defined fibroatheroma-containing index lesions were randomly assigned to rosuvastatin 40 mg versus 10 mg (2:1 ratio). Data were available on 225 patients; 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.

Results:

At baseline, 68% of patients were statin–naïve. Nonstatin medication frequency was typical evidence based, but for an increased use of calcium antagonists (74%). Mean baseline low-density lipoprotein cholesterol (LDL-C) was 106 mg/dl at baseline and at 12 months was 59 mg/dl on 40 mg and 79 mg/dl on 10 mg of rosuvastatin. 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 fibro-fatty 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-thin cap fibroatheroma (55% vs. 29%) decreased significantly. Normalized total (202.9 vs. 188.5; p = 0.001) and percent (51.4 vs. 50.4; p = 0.018) atheroma volumes decreased. Independent predictors of percent NC volume change were body mass index, high-sensitivity C-reactive protein (hs-CRP), and baseline percent NC volume; all p < 0.05). VH-defined percent compositional volume changes in the rosuvastatin 40 mg and 10 mg groups were similar. There was a significant interaction between LDL-C at baseline and reduction in percent NC volume (p for interaction 0.017) by rosuvastatin 40 mg (vs. 10 mg).

Conclusions:

Rosuvastatin reduced NC and plaque volume, and decreased thin-cap fibroatheroma rate. There were no significant differences between high- versus moderate-intensity rosuvastatin and irrespective of previous statin exposure.

Perspective:

The authors present the argument that this study of atheroma volume and content using IVUS at 1 year following high- versus low-dose atorvastatin demonstrating a relationship with hs-CRP, but not change in LDL-C, provides evidence that the reduction in necrotic core volume is related to the pleiotropic anti-inflammatory effect. However, there was a greater change in the 40 mg rosuvastatin group, especially in the setting of a higher baseline LDL-C level.

Clinical Topics: Diabetes and Cardiometabolic Disease, Clinical Topic Collection: Dyslipidemia, Noninvasive Imaging, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Echocardiography/Ultrasound

Keywords: Body Mass Index, C-Reactive Protein, Cholesterol, LDL, Constriction, Pathologic, Coronary Stenosis, Diagnostic Imaging, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Plaque, Atherosclerotic, Primary Prevention, Thallium, Ultrasonography, Interventional


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