The effect of cholesteryl ester transfer protein inhibition on lipids, lipoproteins, and markers of HDL function after an acute coronary syndrome: the dal-ACUTE randomized trial
Language English Country Great Britain, England Media print-electronic
Document type Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
24639426
DOI
10.1093/eurheartj/ehu105
PII: ehu105
Knihovny.cz E-resources
- Keywords
- Coronary disease, Lipids, Lipoproteins,
- MeSH
- ATP Binding Cassette Transporter 1 metabolism MeSH
- Acute Coronary Syndrome drug therapy MeSH
- Amides MeSH
- Anticholesteremic Agents administration & dosage MeSH
- Apolipoproteins metabolism MeSH
- Biomarkers metabolism MeSH
- C-Reactive Protein metabolism MeSH
- Double-Blind Method MeSH
- Esters MeSH
- Cholesterol, HDL metabolism MeSH
- Myocardial Infarction drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Lipoproteins metabolism MeSH
- Lipid Metabolism drug effects MeSH
- Angina, Unstable drug therapy MeSH
- Drug Administration Schedule MeSH
- Sulfhydryl Compounds administration & dosage MeSH
- Cholesterol Ester Transfer Proteins antagonists & inhibitors MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- ABCA1 protein, human MeSH Browser
- ATP Binding Cassette Transporter 1 MeSH
- Amides MeSH
- Anticholesteremic Agents MeSH
- Apolipoproteins MeSH
- Biomarkers MeSH
- C-Reactive Protein MeSH
- CETP protein, human MeSH Browser
- dalcetrapib MeSH Browser
- Esters MeSH
- Cholesterol, HDL MeSH
- Lipoproteins MeSH
- Sulfhydryl Compounds MeSH
- Cholesterol Ester Transfer Proteins MeSH
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.
Baylor College of Medicine Houston TX USA
Charles University Faculty Hospital Hradec Králové Czech Republic
F Hoffmann La Roche Ltd Basel Switzerland
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