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Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial
The Lancet - Early Online Publication, 09/15/2011
Clinical Article
Fayad ZA et al. - Dalcetrapib showed no evidence of a pathological effect related to the arterial wall over 24 months. Moreover, this trial suggests possible beneficial vascular effects of dalcetrapib, including the reduction in total vessel enlargement over 24 months, but long-term safety and clinical outcomes efficacy of dalcetrapib need to be analysed.
Methods- In this phase 2b, double-blind, multicentre trial, patients (aged 18—75 years) with, or with high risk of, coronary heart disease were randomly assigned (1:1) to dalcetrapib 600 mg/day or placebo for 24 months.
- Randomisation was done with a computer-generated randomisation code and was stratified by centre.
- Patients and investigators were masked to treatment.
- Coprimary endpoints were MRI-assessed indices (total vessel area, wall area, wall thickness, and normalised wall index [average carotid]) after 24 months and 18F-fluorodeoxyglucose (18F-FDG) PET/CT assessment of arterial inflammation within an index vessel (right carotid, left carotid, or ascending thoracic aorta) after 6 months, with no-harm boundaries established before unblinding of the trial.
- 189 patients were screened and 130 randomly assigned to placebo (66 patients) or dalcetrapib (64 patients).
- For the coprimary MRI and PET/CT endpoints, CIs were below the no-harm boundary or the adverse change was numerically lower in the dalcetrapib group than in the placebo group.
- MRI-derived change in total vessel area was reduced in patients given dalcetrapib compared with those given placebo after 24 months; absolute change from baseline relative to placebo was -4.01 mm2 (90% CI -7.23 to -0.80; nominal p=0•04).
- The PET/CT measure of index vessel most-diseased-segment target-to-background ratio (TBR) was not different between groups, but carotid artery analysis showed a 7% reduction in most-diseased-segment TBR in the dalcetrapib group compared with the placebo group (-7.3 [90% CI -13.5 to -0.8]; nominal p=0•07).
- Dalcetrapib did not increase office blood pressure and the frequency of adverse events was similar between groups.
