Clinical trial evidence supports the use of intensive statin therapy for patients with coronary artery disease. High doses of potent statins have shown the greatest clinical benefit, but concerns persist regarding the efficacy and safety of achieving very low levels of low-density lipoprotein (LDL) cholesterol. We grouped patients treated with 40 mg of rosuvastatin daily by the LDL cholesterol achieved according to previous work (<40, 40 to <60, 60 to <80, 80 to <100, and > or =100 mg/dl) and by National Cholesterol Education Program targets (<70, 70 to <100, and > or =100 mg/dl) in A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID). The rates of key safety end points, including death, hemorrhagic stroke, and liver and muscle enzyme elevations, and key efficacy end points (atheroma burden) were compared using chi-square testing or Fisher's exact testing. The analysis included 471 patients who had had their LDL cholesterol measured at 3 months, of whom 340 (72.2%) had LDL cholesterol of <70 mg/dl, exhibiting excellent achievement of even the most stringent guideline-based goals. Of these 471 subjects, 192 (40.8%) had LDL cholesterol > or =40 mg/dl but <60 mg/dl, and 57 (12.1%) had LDL cholesterol <40 mg/dl. Adverse events occurred infrequently during the trial, and no pattern appeared relating the frequency of any adverse event to the achieved LDL cholesterol. Similarly, the on-treatment atheroma volume, change in atheroma volume, and high percentage of subjects with atheroma regression did not differ by the achieved LDL cholesterol. In conclusion, although the power to detect such changes was limited, these data showed no clear relation between the LDL cholesterol achieved by intensive statin therapy with rosuvastatin and adverse effects. Atheroma regression occurred in most patients and was not linked to the LDL cholesterol achieved.