ASTEROID trial

Last reviewed 01/2018

• ASTEROID trial
  • evaluating the effect of very high-intensity statin therapy on regression of coronary atherosclerosis
  • study was designed to evaluate the extent of coronary atheroma at baseline and after two years treatment with rosuvastatin 40 mg/day. Outcome measures were the change from baseline to study end in percentage atheroma volume (PAV) [primary outcome measure] and the change in total atheroma volume (TAV) in the sub segment of the coronary artery with the largest plaque volume at baseline (the most diseased segment) [secondary outcome measure]
  • study had an 80% power to detect an expected change of -0.7% in PAV and an 80% power to detect an expected change in normalised total atheroma volume TAV of -3.0 mm^3
  • results:
    • mean baseline low-density lipoprotein cholesterol (LDL-C) level of 130.4 mg/dL declined to 60.8 mg/dL; mean reduction of 53.2% (P<.001)
    • mean high-density lipoprotein cholesterol (HDL-C) level at baseline was 43.1 mg/dL, increasing to 49.0 mg/dL, an increase of 14.7% (P<.001)
    • 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)
    • mean (SD) change in atheroma volume in the most diseased 10-mm subsegment was -6.1 (10.1) mm(3), with a median of -5.6 mm(3) (97.5% CI, -6.8 to -4.0 mm(3)) (P<.001 vs baseline)
    • change in total atheroma volume showed a 6.8% median reduction
    • adverse events were infrequent and similar to other statin trials.
  • the study authors concluded that "..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 intravascular ultrasound (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"
  • limitations of the trial (2):
    • no data on mortality or morbidity
    • lack of control group
    • study defined patients as high risk but many patients were not: only 13% had diabetes mellitus and baseline LDL-C level for enrolled patients was only mildly elevated, the HDL-C level was average, and 17% of patients were not taking aspirin at baseline
    • a comparison of high-dose rosuvastatin with simvastatin would be a more informative study design (3)
    • 98% of patients included in the trial were Caucasian
  • important Safety Issues (2,3,4)
    • rosuvastatin 40mg dose is contraindicated in:
      • asians (3)
      • patients with predisposing risk factors for myopathy or rhabdomyolysis (4)
      • rosuvastatin is not licensed for atherosclerosis – any doctor prescribing for this will be prescribing ‘off-license’ and must take full responsibility
    • CSM/MHRA guidance regarding prescription of rosuvastatin (2,5)
      • all patients (including those who are switching form another statin) must start on the initial dose of 5 mg (or 10mg) of rosuvastatin once daily and should only be titrated to 10mg if considered necessary after a 4 week trial of 5 mg
      • specialist supervision is recommended when 40mg is initiated
  • the 40mg dose should only be necessary for the minority of patients with severe hypercholesterolaemia at high cardiovascular risk
  • a MeReC review of this trial (6) concluded that "..the ASTEROID study does not provide evidence to support a change in practice. Rosuvastatin has no clinical outcome data and prescribing restrictions apply to higher doses. Therefore, it should be reserved for cautious use in difficult-to-treat cases. A statin which has been shown to reduce mortality and morbidity (e.g simvastatin 40mg) is a more appropriate first choice.."

Reference:

1. Nissen SE, Nicholls SJ, Sipahi I et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis. JAMA 2006;295:
2. Keele University Department of Medicines Management (March 2006). Does asteroid make an impact.
3. Blumenthal RS, Kapur NK. Can a Potent Statin Actually Regress Coronary Atherosclerosis? JAMA 2006;295:doi:10.1001/jama.295.13.jed60019.
4. AstraZeneca. Crestor 5mg, 10mg, 20mg and 40mg film-coated tablets . Summary of Product Characteristics 2006
5. CSM/MHRA. New prescribing advice for the 40mg dose of crestor (rosuvastatin). Important Safety Message. 2004.
6. MeReC Extra (May 2006);22.