OBJECTIVES: The purpose of this study was to evaluate the effect of statin treatment on coronary plaque composition and morphology by optical coherence tomography (OCT), grayscale and integrated backscatter (IB) intravascular ultrasound (IVUS) imaging. BACKGROUND: Although previous studies have demonstrated that statins substantially improve cardiac mortality, their precise effect on the lipid content and fibrous cap thickness of atherosclerotic coronary lesions is less clear. While IVUS lacks the spatial resolution to accurately assess fibrous cap thickness, OCT lacks the penetration of IVUS. We used a combination of OCT, grayscale and IB-IVUS to comprehensively assess the impact of pitavastatin on plaque characteristics. METHODS: Prospective serial OCT, grayscale and IB-IVUS of nontarget lesions was performed in 42 stable angina patients undergoing elective coronary intervention. Of these, 26 received 4 mg pitavastatin after the baseline study; 16 subjects who refused statin treatment were followed with dietary modification alone. Follow-up imaging was performed after a median interval of 9 months. RESULTS: Grayscale IVUS revealed that in the statin-treated patients, percent plaque volume index was significantly reduced over time (48.5 ± 10.4%, 42.0 ± 11.1%; p = 0.033), whereas no change was observed in the diet-only patients (48.7 ± 10.4%, 50.4 ± 11.8%; p = NS). IB-IVUS identified significant reductions in the percentage lipid volume index over time (34.9 ± 12.2%, 28.2 ± 7.5%; p = 0.020); no change was observed in the diet-treated group (31.0 ± 10.7%, 33.8 ± 12.4%; p = NS). While OCT demonstrated a significant increase in fibrous cap thickness (140 ± 42 μm, 189 ± 46 μm; p = 0.001), such changes were not observed in the diet-only group (140 ± 35 μm, 142 ± 36 μm; p = NS). Differences in the changes in the percentage lipid volume index (-6.8 ± 8.0% vs. 2.8 ± 9.9%, p = 0.031) and fibrous cap thickness (52 ± 32 μm vs. 2 ± 22 μm, p < 0.001) over time between the pitavastatin and diet groups were highly significant. CONCLUSIONS: Statin treatment induces favorable plaque morphologic changes with an increase in fibrous cap thickness, and decreases in both percentage plaque and lipid volume indexes.