ACC: Confirmation that Rosuvastatin (Crestor) Regresses Coronary Stenoses

By Peggy Peck
CHICAGO, April 1 -- Reversal of coronary stenosis seen by intravascular ultrasound after two years of rosuvastatin (Crestor) treatment has been confirmed in the same patients by quantitative coronary angiograpy, researchers reported here.Christie M. Ballantyne, M.D., of Baylor College of Medicine in Houston, reporting the findings of the ASTEROID trial at the American College of Cardiology meeting, said the results were particularly reassuring because they demonstrate that significant reduction of LDL with a statin can have a clinical impact. The results were published simultaneously online in Circulation.After 24 months, the mean percent diameter stenosis decreased from 37.3±8.4% (median [minimum-maximum] 35.7% [26-73%]) to 36.0±10.1% (median 34.5% [8-74%] P<0.001) and minimum lumen diameter increased from increased from 1.65±0.36 mm (median 1.62 [0.56-2.65] mm) to 1.68±0.38 mm (median 1.67 [0.76-2.77] mm P <0.001).
As Dr. Ballantyne was reporting the ASTEROID findings, AstraZeneca announced that it was shutting down another large clinical trial of rosuvastatin because the JUPITER (Justification for the Use of Statins in Primary Prevention) trial data safety monitoring board had found "unequivocal evidence of a reduction in cardiovascular morbidity and mortality" favoring rosuvastatin over placebo.
At a press conference, Dr. Ballantyne said the timing of the results from his imaging study and halting the JUPITER trial could not have been better. "There has been a lot of debate over the last 24 hours about whether lipid-lowering achieves clinical benefit. I think these two trials provide evidence of the value of lipid-lowering."
Dr. Ballantyne was referring to the debate over data from the ENHANCE study, which found that lipid lowering with ezetimibe/simvastatin (Vytorin) did not slow atherosclerosis as measured by carotid intima-media thickness.
The ASTEROID (A Study to Evaluate the Effect on Intravascular Ultrasound-Derived Coronary Atheroma Burden) trial enrolled 507 coronary artery disease patients who were treated with rosuvastatin at 40 mg/day for 24 months. All patients had a reduction of 50% or less in left main lumen diameter.
Blinded quantitative coronary angiography analysis of percent diameter stenosis and minimum lumen diameter was performed for up to 10 segments of coronary arteries and major branches. The investigators calculated the mean of all lesions at baseline and study end for each patient.
Three hundred and seventy-nine patients had baseline and follow-up angiograms and of those 292 patients had one or more segments with more than a 25% stenosis at baseline that were matched to angiograms at the end of the study.
Rosuvastatin therapy reduced LDL by an average of 53.3% and increased HDL by an average of 13.8%.
The study was limited, he said, by the absence of a control group, but he noted that it was considered unethical to treat patients with advanced coronary artery disease with a placebo. As an alternative, the investigators were blinded to the dates on the angiograms and the images were resequenced using random assignments.
Another limitation was the fact that about a third of the patients did not return for a second angiogram, he said.
The study was funded by AstraZeneca. Dr. Ballantyne said he received research grants from Abbott, ActivBiotics, Gene Logic, GlaxoSmithKline, Integrated Therapeutics, Merck, Pfizer, Schering-Plough, Sanofi-Synthelabo, Takeda, Reliant, and Novartis.
Additional source: CirculationSource reference: Ballantyne CM, et al "Effect of rosuvastatin therapy on coronary arterhy stenoses assess by quantatitive coronary angiography in ASTEROID" Circulation 2008; DOI: 10.1161/CIRCULATIONAHA.108.773747.