Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial

Abstract

Conclusion: Very-high-intensity statin therapy with rosuvastatin can reduce coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). Summary: The authors performed a prospective, open-labeled, blinded end point trial to determine the effect of very-high-intensity statin therapy on coronary atherosclerosis as assessed by IVUS. The study was conducted in 53 community and tertiary medical centers in the United States, Canada, Europe, and Australia. Coronary atheromas were assessed at baseline and after 24 months of treatment. A total of 507 patients had a baseline IVUS examination and received at least one 40-mg dose of rosuvastatin a day. There was no placebo arm of the trial, with all patients receiving 40 mg/d of rosuvastatin. At 24 months, 349 patients had an evaluable IVUS examination. Primary efficacy parameters were a change in atheroma volume percentage measured by IVUS and change in atheroma volume in a 10-mm subsegment of artery with the greatest disease severity at baseline. A second efficacy variable was normalized atheroma volume for the entire artery. At baseline, the mean low-density lipoprotein cholesterol (LDL) was 130.4 ± 34.3 mg/dL. This declined to 60.8 ± 20.0 mg/dL with treatment with rosuvastatin, a mean reduction of 53.2% (P < .001). The mean high-density lipoprotein cholesterol (HDL) level at baseline was 43.1 ± 11.1 mg/dL. This increased to 49.0 ± 12.6 mg/dL with rosuvastatin treatment, an increase of 14.7% (P < .001). The mean change in the percentage of atheroma volume was –0.98% ± 3.15% with a median of –0.79% (97.5% confidence interval [CI], –1.21% to –0.53%), P < .001 compared with baseline. The mean change in atheroma volume in the most diseased 10-mm subsegment was –6.1 ± 10.1 mm3, with a median change of –5.6 mm3 (97.5% CI, –6.8 mm to –.40 mm3), P < .001 compared with baseline. Total atheroma volume showed a 6.8% median reduction, with a mean reduction of –14.7 ± 25.7 mm3 and a median reduction of –12.5 mm3 (95% CI, –15.5 to 10.5 mm3), P < .001 compared with baseline. Comment: This study demonstrates convincing regression of atherosclerosis in the coronary circulation with high-dose statin therapy. The study has some limitations in that there was no placebo control. Also, 22 patients were withdrawn because of ischemic events, and those patients may represent actual progression of atherosclerosis under the treatment protocol. Nevertheless, in the patients evaluated, coronary atherosclerosis was reduced with the high-dose statin therapy used in this study. There were minimal complications and intolerance associated with the drug. It seems clear that high-dose statin therapy is indicated for patients with significant coronary disease. There is no evidence to date, however, that such therapy will benefit patients with cerebrovascular or peripheral arterial disease. Those trials still need to be done.