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.."
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