Key result
Atorvastatin 80 mg significantly reduces carotid plaque inflammation vs. the 10-mg dose.
Why the study?
Preliminary studies indicate that USPIO-enhanced MRI can identify macrophage infiltration in human carotid atheroma in vivo as a surrogate marker of plaque inflammation. This study evaluated whether high-dose versus low-dose atorvastatin produces quantifiable changes in USPIO-enhanced MRI-defined carotid plaque inflammation within the first 3 months of therapy.
Does high-dose atorvastatin (80 mg daily) reduce carotid plaque inflammation as measured by USPIO-enhanced MRI compared to low-dose atorvastatin (10 mg daily) in patients with carotid stenosis >40%?
RCT (n=47)
Double-blind
Balanced
Does high-dose atorvastatin (80 mg daily) reduce carotid plaque inflammation as measured by USPIO-enhanced MRI compared to low-dose atorvastatin (10 mg daily) in patients with carotid stenosis >40%?
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The relatively small patient group tested limits generalization of the dose-response observed in this study. Although the authors exhibit a weak correlation of the MRI data to the microemboli count on transcranial Doppler, the study still does not correlate the MRI findings to any hard clinical end points.”
Aggressive lipid-lowering therapy with 80 mg atorvastatin over 12 weeks significantly reduces carotid plaque inflammation as measured by USPIO-enhanced MRI, whereas 10 mg atorvastatin shows no difference.
Objectives The aim of this study was to evaluate the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on carotid plaque inflammation as determined by ultrasmall superparamagnetic iron oxide (USPIO)-enhanced carotid magnetic resonance imaging (MRI). The hypothesis was that treatment with 80 mg atorvastatin would demonstrate quantifiable changes in USPIO-enhanced MRI-defined inflammation within the first 3 months of therapy. Background Preliminary studies indicate that USPIO-enhanced MRI can identify macrophage infiltration in human carotid atheroma in vivo and hence may be a surrogate marker of plaque inflammation. Methods Forty-seven patients with carotid stenosis >40% on duplex ultrasonography and who demonstrated intraplaque accumulation of USPIO on MRI at baseline were randomly assigned in a balanced, double-blind manner to either 10 or 80 mg atorvastatin daily for 12 weeks. Baseline statin therapy was equivalent to 10 mg of atorvastatin or less. The primary end point was change from baseline in signal intensity (DeltaSI) on USPIO-enhanced MRI in carotid plaque at 6 and 12 weeks. Results Twenty patients completed 12 weeks of treatment in each group. A significant reduction from baseline in USPIO-defined inflammation was observed in the 80-mg group at both 6 weeks (DeltaSI 0.13; p = 0.0003) and at 12 weeks (DeltaSI 0.20; p < 0.0001). No difference was observed with the low-dose regimen. The 80-mg atorvastatin dose significantly reduced total cholesterol by 15% (p = 0.0003) and low-density lipoprotein cholesterol by 29% (p = 0.0001) at 12 weeks. Conclusions Aggressive lipid-lowering therapy over a 3-month period is associated with significant reduction in USPIO-defined inflammation. USPIO-enhanced MRI methodology may be a useful imaging biomarker for the screening and assessment of therapeutic response to "anti-inflammatory" interventions in patients with atherosclerotic lesions. (Effects of Atorvastatin on Macrophage Activity and Plaque Inflammation Using Magnetic Resonance Imaging [ATHEROMA]; NCT00368589).
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Tang et al. (2009) conducted an RCT in Carotid stenosis with plaque inflammation (n=47). Atorvastatin vs. Atorvastatin 10 mg daily was evaluated on Change from baseline in signal intensity (DeltaSI) on USPIO-enhanced MRI in carotid plaque at 6 and 12 weeks (DeltaSI 0.20 at 12 weeks, p=<0.0001). High-dose atorvastatin (80 mg) significantly reduced USPIO-defined carotid plaque inflammation at 6 weeks (DeltaSI 0.13; p=0.0003) and 12 weeks (DeltaSI 0.20; p<0.0001), unlike the 10-mg dose.
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