A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden - ASTEROID

Description:

The goal of the trial was to evaluate the effect of treatment with intensive statin therapy on intravascular ultrasound (IVUS)-assessed atherosclerosis disease progression among patients with angiographic coronary disease.

Study Design

Study Design:

Patients Screened: 1,183
Patients Enrolled: 507
Mean Follow Up: 2 years
Mean Patient Age: Mean age 58.5 years
Female: 29

Patient Populations:

Presence of a coronary angiographic evaluated lesion >20%, IVUS target vessel stenosis <50% and not being treated with angioplasty with a minimum length of 40 mm, and statin-naïve. There were no inclusion or exclusion criteria based on LDL levels.

Exclusions:

Uncontrolled triglyceride levels (≥500 mg/dl) or poorly controlled diabetes (glycosylated hemoglobin levels ≥10%)

Primary Endpoints:

1) Change in percent atheroma volume, and 2) change in nominal atheroma volume in the 10 mm subsegment with the greatest disease severity at baseline

Secondary Endpoints:

Change in normalized total atheroma volume for the entire artery

Drug/Procedures Used:

All patients were treated with rosuvastatin 40 mg in an open-label manner (n = 507). Patients underwent IVUS of a single vessel that had not been intervened upon at baseline. Patients then underwent follow-up IVUS 2 years later to evaluate change in atherosclerosis, which was assessed by a core lab in a time-sequence blinded manner (i.e., it was not known what was baseline and what was the follow-up ultasound image). A total of 349 patients had baseline and follow-up IVUS.

Principal Findings:

Low-density lipoprotein (LDL) levels were reduced from 130.4 mg/dl at baseline to a mean of 60.8 mg/dl during the study (p < 0.001), with 75% of patients achieving an LDL <70 mg/dl. High-density lipoprotein (HDL) levels were increased from 43.1 mg/dl at baseline to 49.0 mg/dl (p < 0.001).

The co-primary endpoint of change in percent atheroma volume was reduced by a mean of 0.98% (p < 0.001 vs. baseline). Regression in percent atheroma volume was observed in 63.6% of patients and progression in 36.4%. The other co-primary endpoint, change in nominal atheroma volume in the 10 mm subsegment with the greatest disease severity at baseline, was also reduced (mean -6.1 mm3, p < 0.001 vs. baseline). Total atheroma volume was also reduced at follow-up by a mean of -14.7 mm3 (p < 0.001). IVUS results were similar in the prespecified subgroups. Adverse events leading to study drug discontinuation included musculoskeletal complaints (3.7%) and cardiovascular disorders (4.3%). There were no cases of rhabdomyolysis.

Interpretation:

Among patients with angiographic coronary disease, treatment with intensive statin therapy with rosuvastatin 40 mg was associated with atherosclerosis regression on IVUS at 2-year follow-up.

Prior IVUS studies have shown a reduction in atherosclerosis progression with intensive statin therapy compared with a more moderate lipid-lowering regimen. However, the present study is the first large-scale study to demonstrate atherosclerosis regression with intensive statin therapy.

One limitation of the present study is the lack of control group. The authors attribute the regression to the very large reductions in LDL and increases in HDL. However, it should be noted that regression in atheroma volume in the most diseased 10 mm subsegment was observed even in patients with an average LDL of 100 mg/d (-6.9 mm3, p = 0.004) and those with an average HDL <35 mg/dl (-5.9 mm3, p < 0.001). The impact of aggressive lipid lowering on clinical events was not fully evaluated in this trial.

References:

Presented by Dr. Steven E. Nissen at the March 2006 ACC Annual Scientific Session, Atlanta, GA.

Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 2006;295:1556-65.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Fluorobenzenes, Atherosclerosis, Plaque, Atherosclerotic, Follow-Up Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Pyrimidines, Constriction, Pathologic, Angioplasty, Rhabdomyolysis, Lipoproteins, LDL, Coronary Angiography, Lipoproteins, HDL, Sulfonamides, Disease Progression


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