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19-09-2011 | Cardiometabolic | Article

Dalcetrapib treatment reduces adverse vascular changes in CHD patients


Free abstract

MedWire News: Study findings suggest that treatment with dalcetrapib, a modulator of cholesteryl ester transfer protein activity, may be associated with favorable vascular changes in patients with or at high risk for coronary heart disease (CHD).

"After 24 months, total vessel area increased less with dalcetrapib than placebo and was accompanied by a reduction in wall area," remark the researchers.

"These imaging results were recorded in the context of an early increase in high-density lipoprotein (HDL) cholesterol concentration of 31% and other potentially beneficial changes in the lipid profile, which were maintained during 24 months," they add.

Zahi Fayad (Mount Sinai School of Medicine, New York, USA) and colleagues conducted a randomized, placebo-controlled, phase 2b study involving 130 patients with or at high risk for CHD, who were aged between 18 and 75 years. Patients received either dalcetrapib 600 mg/day or placebo for 24 months.

At baseline and after 6 months the researchers performed 18F-flurodeoxyglucose (18F-FDG) positron emission tomography with computed tomography (PET/CT) assessment of arterial inflammation within an index vessel (right carotid, left carotid, or ascending thoracic aorta). In addition, the change from baseline in total vessel area, wall area, wall thickness, and normalized wall index was assessed after 24 months using magnetic resonance imaging.

As reported in the Lancet, mean HDL cholesterol and apolipoprotein A-I levels in the dalcetrapib group increased by 26.9% and 6.8%, respectively, relative to placebo.

The median increase in high-sensitivity C-reactive protein was 33% after 24 months of dalcetrapib treatment whereas it was unchanged with placebo.

There was no evidence of a pro-atherogenic effect from dalcetrapib therapy in terms of plaque burden, comment Fayad et al. In the dalcetrapib group, total vessel and wall area decreased by a respective 4.01 and 2.20 mm2 relative to placebo. Furthermore, the dalcetrapib-associated decrease in mean wall thickness from baseline was 0.03 mm.

The authors note that the reductions in arterial inflammation after 6 months identified by PET/CT seemed to be related to a subsequent reduction in the rate of progression of total vessels after 24 months.

They conclude: "Taken together, the data suggest that dalcetrapib might reduce adverse structural changes within the blood vessel via a mechanism relating to reduced vascular inflammation and increased HDL cholesterol concentration."

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By Nikki Withers