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10.1093/eurheartj/ehu319

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suck abstract from ncbi


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pmid25142968
      Eur+Heart+J 2015 ; 36 (1 ): 39-48
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  • Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin #MMPMID25142968
  • Kühnast S ; van der Tuin SJ ; van der Hoorn JW ; van Klinken JB ; Simic B ; Pieterman E ; Havekes LM ; Landmesser U ; Lüscher TF ; Willems van Dijk K ; Rensen PC ; Jukema JW ; Princen HM
  • Eur Heart J 2015[Jan]; 36 (1 ): 39-48 PMID25142968 show ga
  • BACKGROUND: The residual risk that remains after statin treatment supports the addition of other LDL-C-lowering agents and has stimulated the search for secondary treatment targets. Epidemiological studies propose HDL-C as a possible candidate. Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from atheroprotective HDL to atherogenic (V)LDL. The CETP inhibitor anacetrapib decreases (V)LDL-C by ?15-40% and increases HDL-C by ?40-140% in clinical trials. We evaluated the effects of a broad dose range of anacetrapib on atherosclerosis and HDL function, and examined possible additive/synergistic effects of anacetrapib on top of atorvastatin in APOE*3Leiden.CETP mice. METHODS AND RESULTS: Mice were fed a diet without or with ascending dosages of anacetrapib (0.03; 0.3; 3; 30 mg/kg/day), atorvastatin (2.4 mg/kg/day) alone or in combination with anacetrapib (0.3 mg/kg/day) for 21 weeks. Anacetrapib dose-dependently reduced CETP activity (-59 to -100%, P < 0.001), thereby decreasing non-HDL-C (-24 to -45%, P < 0.001) and increasing HDL-C (+30 to +86%, P < 0.001). Anacetrapib dose-dependently reduced the atherosclerotic lesion area (-41 to -92%, P < 0.01) and severity, increased plaque stability index and added to the effects of atorvastatin by further decreasing lesion size (-95%, P < 0.001) and severity. Analysis of covariance showed that both anacetrapib (P < 0.05) and non-HDL-C (P < 0.001), but not HDL-C (P = 0.76), independently determined lesion size. CONCLUSION: Anacetrapib dose-dependently reduces atherosclerosis, and adds to the anti-atherogenic effects of atorvastatin, which is mainly ascribed to a reduction in non-HDL-C. In addition, anacetrapib improves lesion stability.
  • |Animals [MESH]
  • |Anticholesteremic Agents/*pharmacology [MESH]
  • |Atherosclerosis/*prevention & control [MESH]
  • |Atorvastatin [MESH]
  • |Cholesterol Ester Transfer Proteins/metabolism [MESH]
  • |Cholesterol, HDL/drug effects/physiology [MESH]
  • |Disease Progression [MESH]
  • |Drug Combinations [MESH]
  • |Female [MESH]
  • |Heptanoic Acids/administration & dosage/*pharmacology [MESH]
  • |Mice, Transgenic [MESH]
  • |Oxazolidinones/administration & dosage/*pharmacology [MESH]
  • |Pyrroles/administration & dosage/*pharmacology [MESH]


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