Rosuvastatin halts progression but not regression of atherosclerosis in low-risk patients

March 25, 2007

Use of high-dose rosuvastatin is associated with a reduction in the progression of atherosclerosis but not regression of atherosclerosis in low-risk individuals with subclinical atherosclerotic disease, said John R. Crouse III, MD, at the American College of Cardiology's 56th annual scientific session.

Use of high-dose rosuvastatin is associated with a reduction in the progression of atherosclerosis but not regression of atherosclerosis in low-risk individuals with subclinical atherosclerotic disease, said John R. Crouse III, MD, at the American College of Cardiology's 56th annual scientific session.

In the METEOR (Measuring Effects on Intima-Media Thickness: An Evaluation of Rosuvastatin) study, 984 asymptomatic persons with modest thickening of the carotid intima-media, an elevated level of low-density lipoprotein (LDL) cholesterol (mean: 154 mg/dL), and 10-year risk of coronary heart disease of <10% (by virtue of their Framingham risk score) were randomized to rosuvastatin, 40 mg/d, or placebo for 2 years.

A low-risk population was chosen so that a placebo arm could be ethically included, said Dr. Crouse, professor of medicine at Wake Forest University, Winston-Salem, N.C. "The subjects had lipid levels that currently don't require statin therapy," he said.

The primary endpoint was the annual rate of change in carotid intima-media thickness (CIMT) at 12 sites during the 2-year study period as measured by B-mode ultrasound. The hypothesis was that rosuvastatin would be associated with statistically significant regression of CIMT at the end of the 2 years.

Although rosuvastatin significantly slowed progression of maximum CIMT for the 12 carotid sites compared with placebo, statistically significant regression of atherosclerosis did not occur in the rosuvastatin-treated patients.

The maximum change in CIMT was -0.0014 mm/year in the rosuvastatin group, compared with +0.0131 mm/year in the placebo group (p <0.001). The -0.0014 mm/year change in the patients assigned to rosuvastatin was not significantly different from zero (p = 0.32).

The findings indicate that rosuvastatin halted progression but did not induce regression of atherosclerosis in a low-risk population, Dr. Crouse said. "In studying low-risk patients without advanced disease, we may have had a limited opportunity to find regression," he said. Nevertheless, the data do seem to support those of ASTEROID (A Study To Evaluate the Effect of Rosuvastatin On Intravascular Ultrasound-Derived Coronary Atheroma Burden), in which high-dose rosuvastatin caused regression of atherosclerosis in high-risk patients with established coronary heart disease.

The frequency of adverse events was not different between the rosuvastatin and placebo groups. Myalgia was the most common event, occurring in 12.7% of the rosuvastatin group and 12.1% of the placebo group. Elevations in alanine aminotransaminase greater than three times the upper limit of normal on two consecutive occasions occurred in 0.6% of the rosuvastatin group (4 patients) and 0.4% of the placebo group (1 patient).