ASTEROID: Regression of atherosclerosis with rosuvastatin confirmed by QCA

April 07, 2008

Chicago, IL - New findings presented last week at the American College of Cardiology 2008 Scientific Sessions, published simultaneously March 31, 2008 in Circulation, confirm that intensive lipid lowering with rosuvastatin (Crestor, AstraZeneca) 40 mg can regress atherosclerosis[1]. Investigators showed that rosuvastatin significantly reduced LDL-cholesterol levels and raised HDL-cholesterol levels and that these improvements in lipid parameters decreased percent-diameter stenosis and improved mean lumen diameter, as measured by quantitative coronary angiography (QCA).

The study, known as A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound (ASTEROID), was presented by lead investigator Dr Christie Ballantyne (Baylor College of Medicine, Houston, TX), who said that lowering LDL-cholesterol levels to less than 70 mg/dL in patients with coronary disease, as was achieved in this trial, has again been proven beneficial. "The findings," said Ballantyne, "are supportive of the American guidelines that say if you have coronary disease, try to knock the LDL down to less than 70 [mg/dL]. That's what we've been telling physicians, and this is all highly supportive of it."

Ballantyne added that his take on the study, especially in light of the findings from the Effect of Combination Ezetimibe and High-Dose Simvastatin vs Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous FamilialHypercholesterolemia (ENHANCE) study, is that lower LDL-cholesterol levels are better in these patients, but how it is achieved is important.

QCA analysis confirms IVUS findings

First presented in 2006, and reported by heartwire at that time, the ASTEROID investigators showed that intensive lipid lowering with rosuvastatin resulted in a significant regression of coronary atherosclerosis, as measured by intravascular ultrasound (IVUS). After two years of treatment with rosuvastatin, investigators report significant decreases in mean percent-atheroma volume and mean atheroma volume in the most diseased 10-mm vessel subsegment, in addition to decreases in the secondary end point of total atheroma volume.

The purpose of this study, said Ballantyne, was to examine the ability of rosuvastatin to regress atherosclerosis, as measured by QCA, an older technology than the newer, flashier IVUS method. Patients enrolled in the study required coronary angiography for a clinical indication, typically stable or unstable chest pain, or an abnormal functional test. To be included in the trial, patients required one obstruction with more than 20% luminal-diameter narrowing in any coronary vessel as long as the IVUS-targeted vessel had not undergone angioplasty. Patients with lesions with >50% luminal narrowing throughout the segment were excluded, and all patients enrolled in the study were statin-naive.

At two years, treatment with rosuvastatin significantly reduced LDL-cholesterol levels 53.3%, down to 61 mg/dL. HDL-cholesterol levels were significantly increased, from 42.8 mg/dL at baseline to 48.3 mg/dL at two years. In fact, as previously noted, LDL-cholesterol levels at 24 months were the lowest ever achieved in a statin trial. Regarding the QCA analysis, mean-diameter stenosis decreased and mean lumen diameter increased both end points significantly.

Baseline and change in measures of stenosis by QCA during treatment

End point Baseline Two years Mean change from baseline p
Percent-diameter stenosis, % (n=292) 37.3 36.0 -1.3 <0.001
Minimum lumen diameter, mm (n=281) 1.65 1.68 0.03 <0.001

Ballantyne said that 97% of patients in the trial experienced regression or had their atherosclerosis stabilized.

Interestingly, the results of ASTEROID were presented the same day AstraZeneca announced that the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) was stopped. The study, a large, multinational, double-blind, placebo-controlled, randomized clinical trial designed to assess directly whether statin therapy (rosuvastatin 20 mg/day) should be given to apparently healthy individuals with low LDL-cholesterol levels but elevated C-reactive-protein levels, was stopped early because the lipid-lowering agent was shown to be more beneficial than placebo in reducing cardiovascular morbidity and mortality.

Ballantyne said that the surrogate-outcomes data—the reduction in LDL-cholesterol levels, the effects of rosuvastatin on IVUS end points, and the effect of rosuvastatin on diameter stenosis as measured by QCA—and the outcomes data are beginning to line up.

The ASTEROID study, however, was limited, in that there was no control group. Dr Steven Nissen (Cleveland Clinic, OH), who presented the IVUS results two years ago, previously told heartwire that randomizing patients with established coronary disease to placebo or low-dose statin therapy was considered "ethically unacceptable." Because of this, Ballantyne said, there are limitations to the study, but he added that they compensated for the absence of placebo controls with the extensive blinding of pertinent information, as well as the resequencing of examinations to avoid observer bias.

In addition, one-third of the patients did not return for a second angiogram, another limitation of the study, report investigators.

AstraZeneca sponsored the ASTEROID study.

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