Korean Circ J.  2018 Jul;48(7):591-601. 10.4070/kcj.2017.0029.

Effect of Pioglitazone in Combination with Moderate Dose Statin on Atherosclerotic Inflammation: Randomized Controlled Clinical Trial Using Serial FDG-PET/CT

• Choo EH
• Han EJ
• Kim CJ
• Kim SH
• O JH
• Chang K
• Seung KB

• KMID: 2414893
• DOI: http://doi.org/10.4070/kcj.2017.0029

Abstract

BACKGROUND AND OBJECTIVES
Non-statin therapy plus lower intensity statin might be an alternative in patients with coronary artery disease (CAD). A recent data suggested an anti-inflammatory therapy can reduce recurrent cardiovascular events and pioglitazone is also an intriguing inflammatory-modulating agent. However, limited data exist on whether pioglitazone on top of statins further attenuates plaque inflammation.
METHODS
Statin-naïve patients with stable CAD and carotid plaques of ≥3 mm were randomly prescribed moderate dose atorvastatin (20 mg/day), or moderate dose atorvastatin plus pioglitazone (30 mg/day) for 3 months. The primary endpoint was the change in the arterial inflammation of the carotid artery measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) during 3 months.
RESULTS
Of the 41 randomized patients, 33 underwent an evaluation by fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT; 17 atorvastatin plus pioglitazone and 16 atorvastatin patients). The addition of pioglitazone significantly improved the insulin sensitivity and increased the high-density lipoprotein cholesterol after 3 months. Although a reduction in the (FDG) uptake by pioglitazone on top of atorvastatin in carotid arteries with plaque showed marginally statistical significance in the entire patient group (atorvastatin plus pioglitazone; −0.10±0.07 and atorvastatin −0.06±0.04, p=0.058), pioglitazone showed a further reduction of the fluorodeoxyglucose (FDG) uptake among patients who had a baseline FDG uptake above the median (atorvastatin plus pioglitazone; −0.14±0.04 and atorvastatin −0.03±0.03, p < 0.001).
CONCLUSIONS
Pioglitazone demonstrated marginally significant anti-inflammatory effects in addition to moderate dose atorvastatin. This may have been due to the lack of power of the study. However, pioglitazone may have an anti-inflammatory effect in those patients with high plaque inflammation (Trial registry at ClinicalTrials.gov, NCT01341730).

Keyword

Atherosclerosis; Positron emission tomography computed tomography; Carotid stenosis; PPAR gamma; Hydroxymethylglutaryl-CoA reductase inhibitors

MeSH Terms

Arteritis
Atherosclerosis
Atorvastatin Calcium
Carotid Arteries
Carotid Stenosis
Cholesterol
Coronary Artery Disease
Electrons
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors*
Inflammation*
Insulin Resistance
Lipoproteins
PPAR gamma
Atorvastatin Calcium
Cholesterol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lipoproteins
PPAR gamma

Figure

• 

  Figure 1 Study flow chart of the patient enrollment. CAD = coronary artery disease; 18F-FDG-PET/CT = 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

• 

  Figure 2 Representative images of carotid plaque of a patient treated with atorvastatin and pioglitazone. Representative FDG-PET (top), CT (second from top), FDG-PET/CT (third from top) images at baseline (left) and at 3-month follow-up (right) are shown. Average of cross-sectional analysis (bottom) of FDG uptakes of the index vessel (arrow) was the primary endpoint. CT = computed tomography; FDG = fluorodeoxyglucose; FDG-PET = fluorodeoxyglucose positron emission tomography.

• 

  Figure 3 Absolute change in the FDG uptake in the index vessel during a 3-month treatment. (A) The TBR was evaluated in individual patients at baseline and after 3-month treatment with atorvastatin 20 mg (left) and atorvastatin 20 mg plus pioglitazone 30 mg (mid). The absolute change in TBR from baseline (right). (B) Individual changes and the absolute change of the TBR in patients with baseline TBR above the median. FDG = fluorodeoxyglucose; TBR = target-to-background ratio.

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