Author + information
- Received March 4, 2013
- Revision received March 27, 2013
- Accepted April 9, 2013
- Published online September 3, 2013.
- Ahmed Tawakol, MD∗,†,‡∗ (, )
- Zahi A. Fayad, PhD§,‖,¶,
- Robin Mogg, PhD#,
- Achilles Alon, PharmD#,
- Michael T. Klimas, PhD#,
- Hayes Dansky, MD#,
- Sharath S. Subramanian, MD†,‡,
- Amr Abdelbaky, MD†,‡,
- James H.F. Rudd, MD, PhD∗∗,
- Michael E. Farkouh, MD, MSc¶,††,
- Irene O. Nunes, PhD#,
- Chan R. Beals, MD# and
- Sudha S. Shankar, MD#
- ∗Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts
- †Department of Imaging, Massachusetts General Hospital, Boston, Massachusetts
- ‡Harvard Medical School, Boston, Massachusetts
- §Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York
- ‖Department of Radiology, Mount Sinai School of Medicine, New York, New York
- ¶Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York
- #Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey
- ∗∗Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom
- ††Peter Munk Cardiac Centre and Li Ka Shing Knowledge Institute, University of Toronto, Toronto, Ontario, Canada
- ↵∗Reprint requests and correspondence:
Dr. Ahmed Tawakol, MR-PET/CT Program, Massachusetts General Hospital, 165 Cambridge Street, Suite 400, Boston, Massachusetts 02114.
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)
Drs. Tawakol and Fayad received consulting fees, and their institutions received grants from Roche and Merck Sharp & Dohme Corporation, a subsidiary of Merck & Co. Dr. Farkouh received support for travel and his institution received grants from Merck Sharp & Dohme Corporation. Drs. Mogg, Alon, Klimas, Dansky, Nunes, Beals, and Shankar are employees of Merck Sharp & Dohme Corporation, a subsidiary of Merck & Co. Drs. Mogg, Alon, Dansky, Nunes, and Beals own stock in Merck Sharp & Dohme Corporation. Dr. Rudd is supported by the NIHR Cambridge Biomedical Research Center. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Tawakol and Fayad contributed equally to this work.
- Received March 4, 2013.
- Revision received March 27, 2013.
- Accepted April 9, 2013.
- American College of Cardiology Foundation