ASTEROID: IVUS shows regression with rosuvastatin

High-intensity treatment drove LDL levels down to 60.8 mg/dL and increased HDL by 14.7%.

ATLANTA – Aggressive treatment with rosuvastatin was associated with a regression of atherosclerotic burden assessed using intravascular ultrasound.

ASTEROID (A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden) did not have a control group and did not measure hard coronary outcomes like death, MI or stroke.

Steven Nissen, MD, medical director of the Cleveland Clinic Cardiovascular Coordinating Center and Editorial Board member of Cardiology Today’s Noninvasive Imaging section, said this was the first IVUS trial to show “unequivocal” evidence of disease regression.

“IVUS is not a surrogate marker for atherosclerosis. It is coronary atherosclerosis,” Nissen said at the American College of Cardiology 55th Annual Scientific Session. “We’re looking right at the disease up close and personal. When we see less plaque after a treatment period, all the limitations aside, we believe it will be confirmed with a morbidity and mortality benefit.”

The ASTEROID trial enrolled 507 patients from 53 centers in the United States, Canada, Europe and Australia. Patients had to have > 20% stenosis in a major coronary artery; the target vessel had to have < 50% stenosis of about 40 mm in length. Patients could not have undergone prior intervention, and they had to be statin naïve.

All patients were treated with rosuvastatin (Crestor, AstraZeneca) at 40 mg daily. Researchers assessed coronary atheroma burden by IVUS at 24 months.

Cholesterol changes

Of the 507 patients treated with rosuvastatin, 158 withdrew or did not have a viable IVUS reading, which left 349 patients available for evaluation. Nissen said the patients who withdrew were nearly identical to the ones that remained in terms of age (mean age was 58.5), gender (71% were men) and other baseline variables.

LDL at baseline was 130.4 mg/dL. Treatment with rosuvastatin was associated with a reduction of 53.2% to a mean of 60.8 mg/dL.

HDL cholesterol increased by 14.7% from a baseline level of 43.1 mg/dL to 49 mg/dL.

“To our knowledge, this is the lowest LDL level ever achieved during a statin outcome trial and the largest increase in HDL ever observed,” Nissen said.

During an ACC press conference, Roger Blumenthal, MD, director of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease and Editorial Board member of Cardiology Today’s Preventive Cardiology section, said the question of the role of increased HDL in atherosclerosis regression raised by the ASTEROID trial is currently under investigation in the AIM HIGH trial.

“When we have progressively lowered LDL, you probably improve endothelial function of the endothelial cells that line the lumen. We believe from other studies that this improvement in endothelial function may lead to improvements in nitric oxide, which may dilate the arteries in response to stress stimuli,” Blumenthal said.

Regression

Nissen, president of the ACC, said the median change in percent atheroma volume was –0.79% and the change in atheroma volume in the most diseased 10 mm subsegment was –5.6 mm².

When researchers measured percent atheroma volume for the entire cohort, they found that 63.6% of the patients regressed and 36.4% of the patients progressed.

For the most diseased 10 mm subsegment, regression occurred in 78.1% of patients and progression occurred in 21.9% of patients.

The treatment regimen was well tolerated. Liver enzymes were at levels similar to that seen in other statin trials and no cases of rhabdomyolysis were reported. – by Jeremy Moore

For more information:

• Nissen SE. Effect of very low LDL-C levels on regression of coronary atherosclerosis: Results of the ASTEROID. Presented at the American College of Cardiology 55th Annual Scientific Session. March 11-14, 2006. Atlanta.