Long-term effects of maximally intensive statin therapy on changes in coronary atheroma composition: insights from SATURN

Aims To evaluate the effect of long-term maximally intensive statin therapy on indices of coronary atheroma composition in a randomized trial, and how these changes relate to modifications of serum lipoproteins and systemic inflammation. Methods and results The Study of coronary Atheroma by inTravascular Ultrasound: the effect of Rosuvastatin vs. atorvastatiN (SATURN) employed serial intravascular ultrasound (IVUS) measures of coronary atheroma in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg daily for 24 months. Seventy-one patients underwent serial assessment of indices of plaque composition by spectral analysis of the radiofrequency IVUS signal. Changes in low-density lipoprotein cholesterol [LDL-C; -52 (-72,-33) mg/dL, P < 0.001], C-reactive protein [CRP-0.2 (-1, 0.1) mg/L, P = 0.01], and high-density lipoprotein cholesterol [ HDL-C; +2.8 (-0.3, 7.8) mg/dL, P < 0.001] were associated with regression of percent atheroma volume (PAV: 1.6 +/- 3.6%, P < 0.001). A reduction in estimated fibro-fatty tissue volume accompanied atheroma regression (P, 0.001), while dense calcium tissue volume increased (P = 0.002). There were no changes in fibrous or necrotic core tissue volumes. Volumetric changes in necrotic core tissue correlated with on-treatment HDL-C (r = -0.27, P 0.03) and CRP (r = 0.25, P = 0.03) levels. A per-lesion analysis showed a reduction in the number of pathological intimal thickening lesions (defined by >= 3 consecutive IVUS frames containing PAV of >= 40%, predominantly fibro-fatty plaque, with,10% confluent necrotic core and,10% confluent dense calcium) at follow-up (67 vs. 38, P = 0.001). Fibroatheromas and fibrotic lesions remained static in number. Conclusions Changes in indices of atheroma composition accompany regression of coronary atheroma with maximally intensive statin therapy, and associate with anti-inflammatory effects of statins.