AIMS: The effects of cholesteryl ester transfer protein (CETP) inhibition on lipids, inflammation, and markers of high-density lipoprotein (HDL) function, following an acute coronary syndrome (ACS), are unknown. METHODS AND RESULTS: The dal-ACUTE study randomized 300 patients (1 : 1) to dalcetrapib 600 mg/day or placebo within 1 week of an ACS. The primary endpoint was per cent change in HDL-cholesterol (HDL-C) after 4 weeks. Secondary endpoints included apolipoprotein levels, markers of HDL function, and inflammation. Dalcetrapib treatment increased HDL-C and apolipoprotein A1 by 33.7 and 11.8%, respectively (both P < 0.001) and total cholesterol efflux by 9.5% (P = 0.003) after 4 weeks, principally via an increase in non-ATP-binding cassette transporter (ABC) A1-mediated efflux, without statistically significant changes in pre-β1-HDL levels. The increase in total efflux with dalcetrapib correlated most strongly with increases in apolipoprotein A1 and HDL-C (r = 0.46 and 0.43, respectively) rather than the increase in pre-β1-HDL (r = 0.32). Baseline and on-treatment ABCA1-mediated efflux correlated most strongly with pre-β1-HDL levels; in contrast, non-ABCA1-mediated efflux correlated better with apolipoprotein A1 and HDL-C levels. CONCLUSIONS: High-density lipoprotein raised through CETP inhibition with dalcetrapib improves cholesterol efflux, principally via a non-ABCA1-mediated pathway. While HDL-C was increased by one-third, apolipoprotein A1 and total efflux were increased only by one-tenth, supporting the concept of dissociation between improvements in HDL function and HDL-C levels, which may be of relevance to ongoing trials and the development of therapeutic interventions targeting HDL.

• Klíčová slova
• Coronary disease, Lipids, Lipoproteins,
• MeSH
• ABCA1 protein metabolismus   MeSH
• akutní koronární syndrom farmakoterapie   MeSH
• amidy MeSH
• anticholesteremika aplikace a dávkování   MeSH
• apolipoproteiny metabolismus   MeSH
• biologické markery metabolismus   MeSH
• C-reaktivní protein metabolismus   MeSH
• dvojitá slepá metoda MeSH
• estery MeSH
• HDL-cholesterol metabolismus   MeSH
• infarkt myokardu farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoproteiny metabolismus   MeSH
• metabolismus lipidů účinky léků   MeSH
• nestabilní angina pectoris farmakoterapie   MeSH
• rozvrh dávkování léků MeSH
• sulfhydrylové sloučeniny aplikace a dávkování   MeSH
• transportní proteiny pro estery cholesterolu antagonisté a inhibitory   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• ABCA1 protein, human MeSH Prohlížeč
• ABCA1 protein MeSH
• amidy MeSH
• anticholesteremika MeSH
• apolipoproteiny MeSH
• biologické markery MeSH
• C-reaktivní protein MeSH
• CETP protein, human MeSH Prohlížeč
• dalcetrapib MeSH Prohlížeč
• estery MeSH
• HDL-cholesterol MeSH
• lipoproteiny MeSH
• sulfhydrylové sloučeniny MeSH
• transportní proteiny pro estery cholesterolu MeSH