Significant Reductions in Coronary Atherosclerosis with Rosuvastatin Intensive Therapy

March 13, Atlanta—The majority of patients in the ASTEROID trial had regression of atherosclerotic disease associated with a treatment regimen of rosuvastatin 40 mg daily. The intensive treatment was well tolerated, with liver function changes similar to those reported in previous trials with maximal doses of statins. Dr. Steven Nissen of Cleveland Clinic Foundation and the principal investigator presented the trial at the American College of Cardiology meeting in Atlanta. The trial was also simultaneously published early online by the Journal of the American Medical Association (www.jama.com).

Of the 507 enrolled patients, 349 had evaluable serial intravascular ultrasound (IVUS) examinations, using a motorized pullback, taken at baseline and after 24 months of treatment. This prospective, open-label blinded endpoints trial was conducted in 53 community and tertiary care centers in the US, Canada, Europe, Australia, with enrollment from November 2002 to October 2003.

The mean reduction in LDL-C from baseline was 53.2% (from 130.4 mg/dL to 60.8 mg/dL; p<0.001) and the mean increase in HDL-C was 14.7% (from 43.1 mg/dL to 49.0 mg/dL; p<0.001).

The mean change in the primary endpoint of percent atheroma volume (PAV)
 was -0.98%, and the median change was -0.79% (p<0.001 compared to baseline).
Disease regression was seen in 63.6% of patients compared to disease progression in 36.4% for the change in PAV.

For the other pre-specified primary endpoint, the mean change in atheroma volume in the 10-mm subsegment with the greatest disease severity, there was a 9.1% median reduction. The mean change was -6.1 mm3, and the median change was -5.6 mm3 (p<0.001 compared to baseline). Disease progression was seen in 78.1% of patients had regression, while 21.9% had progression for this endpoint.

A 6.8% median reduction in total atheroma volume (TAV) was found for the secondary endpoint of the mean change in normalized total atheroma volume. The mean change in TAV was -14.7 mm3 and the median change was -12.5 mm3 (p<0.001 compared to baseline).

The mean age of the study patients was 58.5 years, most were male and of White race (70.2% and 96.8%, respectively), and the mean body mass index was 28.4. Prior medical history included hypertension in 96%, diabetes in 13.2%, acute coronary syndromes in 17.2% and a myocardial infarction in 24.6%. Concomitant drug use comprised aspirin in 83.7%, ACE inhibitors in 53.3%, angiotensin receptor blockers in 18.3%, and beta blockers in 84.2%.

Patients were statin naïve, that is, did not have statin therapy for ≥3 months in the prior 12 months. A 4-week washout period was required of patients treated with any lipid-lowering medication within the prior 4 weeks.

“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 HDL-C in the current study suggest that therapies designed to simultaneously lower LDL-C while raising HDL-C have the potential to substantially reduce lesion burden in patients with established disease,” the authors write.

“The current study supports several conclusions. For secondary prevention patients, very intensive statin therapy using 40 mg/d 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 conclude.

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