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The ASTEROID Trial

Steven E. Nissen, MD; Stephen J. Nicholls, MBBS, PhD; Ilke Sipahi, MD; Peter Libby, MD; Joel S. Raichlen, MD; Christie M. Ballantyne, MD; Jean Davignon, MD; Raimund Erbel, MD; Jean Charles Fruchart, PhD; Jean-Claude Tardif, MD; Paul Schoenhagen, MD; Tim Crowe, BS; Valerie Cain, MS; Kathy Wolski, MPH; Marlene Goormastic, MPH; E. Murat Tuzcu, MD; for the ASTEROID Investigators

JAMA. 2006;295:1556-1565. Published online March 13, 2006 (doi:10.1001/jama.295.13.jpc60002).

Context  Prior intravascular ultrasound (IVUS) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent atheroma volume (PAV), the most rigorous IVUS measure of disease progression and regression.

Objective  To assess whether very intensive statin therapy could regress coronary atherosclerosis as determined by IVUS imaging.

Design and Setting  Prospective, open-label blinded end-points trial (A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden [ASTEROID]) was performed at 53 community and tertiary care centers in the United States, Canada, Europe, and Australia. A motorized IVUS pullback was used to assess coronary atheroma burden at baseline and after 24 months of treatment. Each pair of baseline and follow-up IVUS assessments was analyzed in a blinded fashion.

Patients  Between November 2002 and October 2003, 507 patients had a baseline IVUS examination and received at least 1 dose of study drug. After 24 months, 349 patients had evaluable serial IVUS examinations.

Intervention  All patients received intensive statin therapy with rosuvastatin, 40 mg/d.

Main Outcome Measures  Two primary efficacy parameters were prespecified: the change in PAV and the change in nominal atheroma volume in the 10-mm subsegment with the greatest disease severity at baseline. A secondary efficacy variable, change in normalized total atheroma volume for the entire artery, was also prespecified.

Results  The mean (SD) baseline low-density lipoprotein cholesterol (LDL-C) level of 130.4 (34.3) mg/dL declined to 60.8 (20.0) mg/dL, a mean reduction of 53.2% (P<.001). Mean (SD) high-density lipoprotein cholesterol (HDL-C) level at baseline was 43.1 (11.1) mg/dL, increasing to 49.0 (12.6) mg/dL, an increase of 14.7% (P<.001). The mean (SD) change in PAV for the entire vessel was –0.98% (3.15%), with a median of –0.79% (97.5% CI, –1.21% to –0.53%) (P<.001 vs baseline). The mean (SD) change in atheroma volume in the most diseased 10-mm subsegment was –6.1 (10.1) mm³, with a median of –5.6 mm³ (97.5% CI, –6.8 to –4.0 mm³) (P<.001 vs baseline). Change in total atheroma volume showed a 6.8% median reduction; with a mean (SD) reduction of –14.7 (25.7) mm³, with a median of –12.5 mm³ (95% CI, –15.1 to –10.5 mm³) (P<.001 vs baseline). Adverse events were infrequent and similar to other statin trials.

Conclusions  Very high-intensity statin therapy using rosuvastatin 40 mg/d achieved an average LDL-C of 60.8 mg/dL and increased HDL-C by 14.7%, resulting in significant regression of atherosclerosis for all 3 prespecified IVUS measures of disease burden. Treatment to LDL-C levels below currently accepted guidelines, when accompanied by significant HDL-C increases, can regress atherosclerosis in coronary disease patients. Further studies are needed to determine the effect of the observed changes on clinical outcome.

Trial Registration  ClinicalTrials.gov Identifier: NCT00240318

Author Affiliations: Departments of Cardiovascular Medicine (Drs Nissen, Nicholls, Sipahi, Schoenhagen, and Tuzcu, Mr Crowe, and Mss Wolski and Goormastic) and Diagnostic Radiology (Dr Schoenhagen), Cleveland Clinic Lerner School of Medicine, Cleveland, Ohio; Donald W. Reynolds Cardiovascular Clinical Research Center, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass (Dr Libby); AstraZeneca, Wilmington, Del (Dr Raichlen and Ms Cain); Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, Tex (Dr Ballantyne); Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Montreal, Quebec (Dr Davignon); Department of Cardiology, Universität Duisburg-Essen, Duisburg, Germany (Dr Erbel); Département de Recherche sur les Lipoproteines et l’Atherosclerose, Pasteur de Lille, Inserm U545 et Faculté de Pharmacie, Université du Droit et de la Santé de Lille 2, Lille, France (Dr Fruchart); and MHI Research Center, Montreal Heart Institute, Montreal, Quebec (Dr Tardif).

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