Journal Article

Comparison of Atorvastatin 5 and 20 mg/d for Reducing F-18 Fluorodeoxyglucose Uptake in Atherosclerotic Plaques on Positron Emission Tomography/Computed Tomography: A Randomized, Investigator-Blinded, Open-Label, 6-Month Study in Japanese Adults Scheduled for Percutaneous Coronary Intervention

Ishii, Hideki, Takahashi, Hiroshi, Toriyama, Takanobu, Hayashi, Mutsuharu, Nishio, Masami, Tanaka, Miho, Aoyama, Toru, Matsubara, Tatsuaki, Tamaki, Tsuneo, Yoshikawa, Daiji, Amano, Tetsuya, Murohara, Toyoaki

2010

Overview

F-18 fluorodeoxyglucose ( 18F-FDG) positron emission tomography (PET) is a useful tool for the detection of local inflamed atherosclerotic lesions. This study used hybrid PET/computed tomography (CT) to examine the effects of 2 doses of atorvastatin on 18F-FDG uptake in atherosclerotic plaques in Japanese adults with stable angina pectoris who were scheduled to undergo percutaneous coronary intervention (PCI). This was a prospective, randomized, investigator-blinded, open-label study in patients with dyslipidemia (total cholesterol ≥220 mg/dL and/or LDL-C ≥140 mg/dL) who were scheduled to undergo PCI for stable angina pectoris and had not received any lipid-lowering drugs within 1 year before enrollment. Patients were randomly allocated to receive atorvastatin 5 or 20 mg/d for 6 months. At baseline (the day after PCI), 18F-FDG uptake in the ascending aorta and femoral artery was determined using PET/CT imaging, and the mean target-to-background ratio (TBR) was calculated in individual plaques. The same regions were assessed by PET/CT after 6 months of treatment. Changes from baseline to follow-up in the lipid profile, serum malondialdehyde-modified LDL-C (MDA–LDL-C), and serum high-sensitivity C-reactive protein (hs-CRP) were also examined. Drug adherence, adverse events, and changes in medications were monitored at monthly outpatient visits. Of 32 patients initially screened, 2 were excluded due to newly diagnosed cancer; thus, 30 patients were randomly assigned to treatment, 15 in each group. Patients were predominantly male (18 [60%]), with a mean (SD) age of 54 (11) years, mean body weight of 65 (12) kg, and mean total cholesterol, HDL-C, and triglyceride concentrations of 240 (29), 48 (14), and 180 (102) mg/dL, respectively. After 6 months, the 20-mg group had significant reductions from baseline in mean (SD) TBR in the ascending aorta (from 1.15 [0.14] to 1.05 [0.12]; percent change, −7.9% [9.4%]; P = 0.007) and the femoral artery (from 1.12 [0.11] to 1.02 [0.11]; percent change, −9.9% [13.8%]; P = 0.012). The corresponding changes from baseline were not statistically significant in the 5-mg group. The differences in percent change in TBR in the 2 locations were not significant between groups. When data from the 2 groups were combined, the overall reduction in TBR from baseline to 6 months was significant in both the ascending aorta ( P = 0.003) and the femoral artery ( P = 0.021). The decreases in TBR in both arteries were significantly correlated with reductions in LDL-C (ascending aorta: r 2 = 0.230 [ P = 0.012]; femoral artery: r 2 = 0.338 [ P = 0.003]), MDA–LDL-C (ascending aorta: r 2 = 0.183 [ P = 0.028]; femoral artery: r 2 = 0.247 [ P = 0.010]), and hs-CRP (ascending aorta: r 2 = 0.132 [ P = 0.048]; femoral artery: r 2 = 0.271 [ P = 0.007]). One patient in the 5-mg group and 2 patients in the 20-mg group had ∼2-fold increases in serum aminotransferases on a single occasion; however, no specific musculoskeletal or hepatic adverse events were observed, and aminotransferase values decreased to within normal ranges without changes in the atorvastatin dose. Six months of treatment with atorvastatin 20 mg, but not 5 mg, was associated with a significant reduction in TBR in the ascending aorta and femoral artery in these Japanese adults with dyslipidemia undergoing PCI for stable angina pectoris. University Hospital Medical Information Network Clinical Trials Registry identifier: C000000371.

• Publisher: EM Inc USA,Elsevier
• Subject: Angina Pectoris - complications / Angina Pectoris - surgery / Angioplasty, Balloon, Coronary / Anticholesteremic Agents - administration & dosage / Anticholesteremic Agents - therapeutic use / Aorta - diagnostic imaging / Aorta - metabolism / atherosclerosis / Atherosclerosis (general aspects, experimental research) / Atherosclerosis - complications / Atherosclerosis - diagnostic imaging / Atherosclerosis - drug therapy / Atorvastatin Calcium / Biological and medical sciences / Blood and lymphatic vessels / Cardiology. Vascular system / Dose-Response Relationship, Drug / Dyslipidemias - complications / Dyslipidemias - drug therapy / Dyslipidemias - metabolism / Female / Femoral Artery - diagnostic imaging / Femoral Artery - metabolism / Fluorodeoxyglucose F18 - pharmacokinetics / Heptanoic Acids - administration & dosage / Heptanoic Acids - therapeutic use / Humans / Internal Medicine / lipids / Male / Medical Education / Medical sciences / Middle Aged / Pharmacology. Drug treatments / plaque / Positron-Emission Tomography / Prospective Studies / Pyrroles - administration & dosage / Pyrroles - therapeutic use / statin / Treatment Outcome