Intensification of Statin Therapy Rapidly Reduces Atherosclerotic Inflammation
Statin therapy produced significant rapid dose-dependent reductions in 2-18F-fluoro-2-deoxy-D-glucose (FDG) uptake that may represent changes in atherosclerotic plaque inflammation, according to a new study published in the Journal of the American College of Cardiology.
The study randomized 83 adults with risk factors or with established atherosclerosis, who were not taking high-dose statins, to atorvastatin 10 mg vs. 80 mg. FDG-positron emission tomography/computed tomography (FDG-PET/CT) imaging of the ascending thoracic aorta and carotid arteries was performed at baseline, four weeks and 12 weeks after randomization. Target-to-background ratio (TBR) of FDG uptake within the artery wall was assessed while blinded to time points and treatment.
Overall, the study investigators observed a dose response in the reduction in FDG uptake between the high and low dose statin groups as early as four weeks after randomization. At 12 weeks a greater reduction in FDG uptake was observed in patients randomized to atorvastatin 80 mg vs. 10 mg, with significant additional reduction in FDG uptake within the most diseased segment (MDS) of the index vessel (10.6%, [2.2%, 18.3%], p=0.01). In addition, significant, dose-dependent reductions from baseline were observed for total plasma cholesterol, LDL, and triglycerides. However, no statistically significant, dose-dependent increases in HDL were observed.
"These findings provide evidence of a rapid reduction in vascular inflammation with statin therapy and provide new insights regarding the graded reductions in vascular plaque activity as it relates to increases in statin doses," the investigators said. "The results also confirm the ability of PET imaging as a tool to detect changes in vascular inflammation early in the course of treatment, something not as well validated with other noninvasive imaging methods."
That being said, the investigators did caution that it remains unclear whether lowering plaque inflammation is a mechanism by which statin therapy decreases cardiovascular events or even whether reducing arterial inflammation translates into clinical benefit at all. They recommend future studies wherein imaging is embedded within clinical endpoint trials to evaluate the relationship between plaque inflammation and clinical events. "Should a relationship between reductions in plaque inflammation and reductions in clinical cardiovascular endpoints be proven then targeting plaque inflammation may find a central role in cardiovascular therapy," they note.
"The authors should be congratulated on performing this interesting and well-designed trial, which nicely demonstrates the usefulness of FDG-PET to study drug effect on atherosclerotic plaques in vivo," said Bernhard L. Gerber MD, PhD, FACC, in a corresponding editorial comment. "Further studies employing similar methodology will enhance our understanding on the mode of action and efficacy of new anti-atherosclerosis drugs."
Keywords: Inflammation, Atherosclerosis, Plaque, Atherosclerotic, Carotid Arteries, Risk Factors, Heptanoic Acids, Deoxyglucose, Positron-Emission Tomography, Pyrroles, Cholesterol, Triglycerides, United States
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