Effect of Very High-Intensity Statin Therapy on Regression of Coronary Atherosclerosis (ASTEROID Trial)

The ASTEROID (A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden) trial enrolled 507 patients with established CAD and treated all with rosuvastatin 40 mg daily for 24 months, with serial IVUS at baseline and follow-up.

Rosuvastatin 40 mg reduced LDL-C by 53.2% (median achieved LDL-C: 60.8 mg/dL) and increased HDL-C by 14.7%. Serial IVUS demonstrated significant plaque regression in two primary endpoints: mean percent atheroma volume decreased by 0.98 percentage points, and total atheroma volume decreased by 6.8 mm³. Both changes were highly significant by paired analysis.

ASTEROID was the first trial to demonstrate unequivocal coronary plaque regression with statin therapy using serial IVUS — prior trials had shown only slowing of progression (CAMELOT, REVERSAL placebo arm) or halted progression (REVERSAL atorvastatin arm). The results established that very high-intensity statin therapy not only stops progression but actively reverses established atherosclerotic burden.

The uncontrolled design — no placebo arm, all patients treated — is the principal limitation, as it prevents attributing regression entirely to rosuvastatin rather than regression to mean. However, the effect size and consistency across prespecified subgroups support a treatment effect.

We rate the evidence strong on clinical significance. A landmark proof-of-concept trial demonstrating that aggressive LDL-C lowering with high-dose rosuvastatin reverses coronary plaque — the foundational imaging evidence for aggressive statin therapy targets.