Conclusions : CETP inhibitors are not associated with an increased risk of MACE or all-cause mortality .
There is a trend towards small reductions in nonfatal MI and cardiovascular death , though the clinical importance of such reductions is likely modest
Background : Cholesteryl ester transfer protein ( CETP ) inhibitors increase serum high-density lipoprotein cholesterol ( HDL-c ) concentration ; however , their impact on cardiovascular outcomes is not clear .
This systematic review examines the effect of CETP inhibitors on serum lipid profiles , cardiovascular events , and all-cause mortality .
Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial
BACKGROUND Dalcetrapib modulates cholesteryl ester transfer protein ( CETP ) activity to raise high-density lipoprotein cholesterol ( HDL-C ) . After the failure of torcetrapib it was unknown if HDL produced by interaction with CETP had pro-atherogenic or pro-inflammatory properties . dal-PLAQUE is the first multicentre study using novel non-invasive multimodality imaging to assess structural and inflammatory indices of atherosclerosis as primary endpoints . METHODS In this phase 2b , double-blind , multicentre trial , patients ( aged 18 - 75 years ) with , or with high risk of , coronary heart disease were r and omly assigned ( 1:1 ) to dalcetrapib 600 mg/day or placebo for 24 months . R and omisation was done with a computer-generated r and omisation code and was stratified by centre . Patients and investigators were masked to treatment . Co primary endpoints were MRI-assessed indices ( total vessel area , wall area , wall thickness , and normalised wall index [ average carotid ] ) after 24 months and (18)F-fluorodeoxyglucose ( (18)F-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 . Analysis was by intention to treat . This trial is registered at Clinical Trials.gov , NCT00655473 . FINDINGS 189 patients were screened and 130 r and omly assigned to placebo ( 66 patients ) or dalcetrapib ( 64 patients ) . For the co primary 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 mm(2 ) ( 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 . INTERPRETATION 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 . FUNDING F Hoffmann-La Roche
Conclusions : CETP inhibitors are not associated with an increased risk of MACE or all-cause mortality .
There is a trend towards small reductions in nonfatal MI and cardiovascular death , though the clinical importance of such reductions is likely modest
Background : Cholesteryl ester transfer protein ( CETP ) inhibitors increase serum high-density lipoprotein cholesterol ( HDL-c ) concentration ; however , their impact on cardiovascular outcomes is not clear .
This systematic review examines the effect of CETP inhibitors on serum lipid profiles , cardiovascular events , and all-cause mortality .