Patients treated with very intensive statin therapy lowered low-density cholesterol levels on average by about 50 percent, increased high-density cholesterol levels by 15 percent, and showed regression of coronary atherosclerosis, according to a presentation at the annual meeting of the American College of Cardiology.

Prior intravascular ultrasound trials had demonstrated slowing or halting of atherosclerosis progression with statin therapy but had not shown convincing evidence of atherosclerosis regression, as measured using percent atheroma volume, the most rigorous indicator of disease progression and regression.

Steven E. Nissen, MD, of the Cleveland Clinic, and colleagues with the ASTEROID Trial conducted a study to determine the effects of high-intensity statin therapy on intravascular ultrasound-derived measures of coronary atherosclerosis regression.

Rosuvastatin is one of the most recently introduced statins and typically produces greater reductions in low-density lipoprotein cholesterol and larger increases in high-density lipoprotein cholesterol than previously available agents. The trial was performed at 53 community and tertiary care centers in the United States, Canada, Europe, and Australia.

Coronary atheroma burden was measured at baseline and after 24 months of treatment. Between November 2002 and October 2003, 507 patients had a baseline intravascular ultrasound examination and received at least 1 dose of study drug, rosuvastatin, 40 mg/daily. After 24 months, 349 patients had evaluable serial ultrasound examinations.

The researchers found that the average baseline low-density cholesterol level of 130.4 mg/dL declined to 60.8 mg/dL, an average reduction of 53.2 percent. The average high-density cholesterol level at baseline was 43.1 mg/dL, increasing to 49.0 mg/dL, an increase of 14.7 percent.

For the primary efficacy parameter of change in percent atheroma volume, the average decrease was ?0.98 percent; 63.6 percent of patients showed regression of atherosclerosis. For the second primary efficacy parameter, change in atheroma volume in the 10-mm subsegment with the greatest disease severity, there was a median reduction of 9.1 percent in atheroma volume; 78.1 percent of patients demonstrated regression of atherosclerosis. The secondary efficacy parameter, change in total atheroma volume, showed a 6.8 percent median reduction. Adverse events were infrequent and similar to those reported in other statin trials.

“We believe that the current study has important implications for understanding the pathophysiology and optimal treatment of coronary artery disease. Traditional thinking has viewed atherosclerosis as an inexorably progressive disease for which even the most active therapies can merely slow advancement. The current study suggests that there is potential for a more optimistic strategy, in which aggressive lipid-modulating strategies can actually reverse the atherosclerotic disease process. The observed increases in high-density cholesterol in the current study suggest that therapies designed to simultaneously lower low-density cholesterol while raising high-density cholesterol have the potential to substantially reduce lesion burden in patients with established disease,” the authors wrote.

“The current study supports several conclusions. For secondary prevention patients, very intensive statin therapy using 40 mg/day of rosuvastatin in patients with preexisting coronary disease reduced LDL-C to 60.8 mg/dL while raising HDL-C by 14.7 percent. These changes were larger in magnitude than has been observed in previous statin trials. The very low LDL-C levels and increase in HDL-C levels resulted in significant regression in atheroma burden for all 3 primary and secondary efficacy parameters. This very intensive statin regimen was well tolerated. These observations support the recommendation to administer very intensive statin therapy for high-risk patients with established coronary disease,” the researchers concluded.

The full report will appear in the April 5th issue of the Journal of the American Medical Association (JAMA).