Anti-inflammatory and morphologic effects of pitavastatin on carotid arteries and thoracic aorta evaluated by integrated backscatter trans-esophageal ultrasound and PET/CT: a prospective randomized comparative study with pravastatin (EPICENTRE study)

Abstract

Background: We sought to evaluate the effects of a strong lipophilic statin (pitavastatin) on plaque components and morphology assessed by transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE), as well as plaque inflammation assessed by 18F-fluorodeoxyglucose (FDG) PET/CT in the thoracic aorta and the carotid artery. Furthermore, we compared the effects of pitavastatin with those of mild hydrophilic statin (pravastatin).

Methods: We examined atherosclerotic plaques in the thoracic aorta by TEE and those in the carotid artery by integrated backscatter (IBS)-TTE and PET/CT. We identified the target plaque, where there was macrophage infiltration and inflammation, by strong FDG uptake in the thoracic aorta and carotid arteries and measured maximum standard uptake values (max SUV) by PET/CT. We measured the intima-media thickness (IMT) and the corrected IBS (cIBS) values in the intima-media complex by TEE and TTE at the same site of FDG accumulation by PET/CT.

Results: Patients were randomly divided into two treatment groups: a pitavastatin group (PI group: n =10, 68.4 ± 5.1 years) and a pravastatin group (PR group: n =10, 63.9 ± 11.2 years). The same examinations were performed after six months at the same site in each patient. We used calculated target-to-background ratio (TBR) to measure max SUV of plaques and evaluated percent change of TBR. There was no significant difference in low density lipoprotein-cholesterol, TBR, IMT and cIBS values in plaques at baseline between the PI and PR groups. After treatment, there was greater improvement in TBR, cIBS values and IMT in the PI group than the PR group.

Conclusions: The pravastatin treatment was less effective on plaque inflammation than pitavastatin treatment. This trend was the same in the carotid arteries and the thoracic aorta. Pitavastatin not only improved the atherosis as measured by IMT and cIBS values but also attenuated inflammation of plaques as measured by max SUV at the same site. The present study indicated that pitavastatin has stronger effects on the regression and stabilization of plaques in the thoracic aorta and carotid arteries compared with pravastatin.

Figure 1

Correlation between the changes in each parameter from baseline to 6 months and the changes in low density lipoprotein cholesterol and high density lipoprotein cholesterol. Red dots indicate pravastatin group and blue dots indicate pitavastatin group.

Figure 2

PET: positron emission tomography, TEE: trans-esophageal echocardiography, TBR: target-to-background ratio, IMT: intima-media thickness, cIBS: corrected integrated backscatter.

Figure 3

PET/CT and ultrasound parameters, TBR: target-to-background ratio, IMT: intima-media thickness, cIBS: corrected integrated backscatter, *p < 0.05 vs baseline, ^† p < 0.05 vs pravastatin.