Rationale and design of dal-PLAQUE: a study assessing efficacy and safety of dalcetrapib on progression or regression of atherosclerosis using magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography/computed tomography

Abstract

dal-PLAQUE is a placebo-controlled multicenter study designed to assess the effect of dalcetrapib on imaging measures of plaque inflammation and plaque burden. dal-PLAQUE is a multimodality imaging study in the context of the large dal-HEART Program. Decreased high-density lipoprotein cholesterol is linked to increased risk of coronary heart disease (CHD). Dalcetrapib, a compound that increases high-density lipoprotein cholesterol by modulating cholesteryl ester transfer protein, is being studied to assess if it can reduce the progression of atherosclerotic disease and thereby decrease cardiovascular morbidity and mortality. Patients with CHD or CHD-risk equivalents were randomized to receive 600 mg dalcetrapib or placebo daily for 24 months, in addition to conventional lipid-lowering medication and other medications for cardiovascular risk factors. The primary outcomes are the effect of dalcetrapib on 18F-fluorodeoxyglucose positron emission tomography target-to-background ratio after 6 months and magnetic resonance imaging (MRI) plaque burden (wall area, wall thickness, total vessel area, and wall area/total vessel area ratio) after 12 months. Secondary objectives include positron emission tomography target-to-background ratio at 3 months and MRI plaque burden at 6 and 24 months; plaque composition at 6, 12, and 24 months; and aortic compliance at 6 months. A tertiary objective is to examine the dynamic contrast-enhanced MRI parameters of plaque neovascularization. In total, 189 subjects entered screening, and 130 were randomized. dal-PLAQUE will provide important information on the effects of dalcetrapib on markers of inflammation and atherosclerotic plaque burden and, thereby, on the safety of cholesteryl ester transfer protein modulation with dalcetrapib. Results are expected in 2011.

Figure 1

dal-PLAQUE study design and timeline of imaging assessments (see text for details).

Figure 2

Sample 18F-FDG-PET/CT images of carotids. Transaxial (A) and coronal orientations (B). CT (i), fused PET/CT images (ii), and PET (iii). Blue arrows indicate inflammation in both carotids.

Figure 3

Sample MRIs. A, Cross-sectional carotid images: T2 weighted (i), proton density (PD) weighted (ii), and DCE–area under the curve (iii) 7 minutes. B, Cross-sectional abdominal aorta images: T1 weighted (i), T2 weighted (ii), and PD weighted (iii). * indicates lipid-rich necrotic core; white arrows indicate calcification, and black arrow indicates increased vessel wall neovascularization.