Intensification of Statin Therapy Results in a Rapid Reduction in Atherosclerotic Inflammation

• Published in: Journal of the American College of Cardiology 2013-09, Vol.62 (10), p.909-917
• Main Authors: Tawakol, Ahmed, MD, Fayad, Zahi A., PhD, Mogg, Robin, PhD, Alon, Achilles, PharmD, Klimas, Michael T., PhD, Dansky, Hayes, MD, Subramanian, Sharath S., MD, Abdelbaky, Amr, MD, Rudd, James H.F., MD, PhD, Farkouh, Michael E., MD, MSc, Nunes, Irene O., PhD, Beals, Chan R., MD, Shankar, Sudha S., MD
• Format: Article
• Language: English
• Subjects: atherosclerosis; atorvastatin; Body mass index; Calcification; Cardiology; Cardiovascular; Cardiovascular disease; Cholesterol; Confidence intervals; Diabetes; Drug therapy; Family medical history; FDG; Gene expression; inflammation; Internal Medicine; Lipoproteins; plaque; Statins
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2013.04.066

Objectives The study sought to test whether high-dose statin treatment would result in greater reductions in plaque inflammation than low-dose statins, using fluorodeoxyglucose-positron emission tomography/computed tomographic imaging (FDG-PET/CT). Background Intensification of statin therapy reduces major cardiovascular events. Methods Adults with risk factors or with established atherosclerosis, who were not taking high-dose statins (n = 83), were randomized to atorvastatin 10 versus 80 mg in a double-blind, multicenter trial. FDG-PET/CT imaging of the ascending thoracic aorta and carotid arteries was performed at baseline, 4, and 12 weeks after randomization and target-to-background ratio (TBR) of FDG uptake within the artery wall was assessed while blinded to time points and treatment. Results Sixty-seven subjects completed the study, providing imaging data for analysis. At 12 weeks, inflammation (TBR) in the index vessel was significantly reduced from baseline with atorvastatin 80 mg (% reduction [95% confidence interval]: 14.42% [8.7% to 19.8%]; p < 0.001), but not atorvastatin 10 mg (% reduction: 4.2% [–2.3% to 10.4%]; p > 0.1). Atorvastatin 80 mg resulted in significant additional relative reductions in TBR versus atorvastatin 10 mg (10.6% [2.2% to 18.3%]; p = 0.01) at week 12. Reductions from baseline in TBR were seen as early as 4 weeks after randomization with atorvastatin 10 mg (6.4% reduction, p < 0.05) and 80 mg (12.5% reduction, p < 0.001). Changes in TBR did not correlate with lipid profile changes. Conclusions Statin therapy produced significant rapid dose-dependent reductions in FDG uptake that may represent changes in atherosclerotic plaque inflammation. FDG-PET imaging may be useful in detecting early treatment effects in patients at risk or with established atherosclerosis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261 )