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EVACETRAPIB A hope in order to treat cardiovascular disease… Laurent MAGNIES Claire JAGODZINSKI
INTRODUCTION ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],JAMA – Nov16, 2011 – Vol 306 – N°19
Lipid Exchange ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Journal of Lipid Research – Vol 52 – Sept 25, 2011
CETP Activity ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Journal of Lipid Research – Vol 52 – Sept 25, 2011
Preclinical Studies (1) ,[object Object],[object Object],[object Object],[object Object],Journal of Lipid Research – Vol 52 – Sept 25, 2011
Preclinical Studies (2) ,[object Object],[object Object],[object Object],[object Object],[object Object],Journal of Lipid Research – Vol 52 – Sept 25, 2011
Journal of Lipid Research – Vol 52 – Sept 25, 2011
Preclinical Studies (2) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Journal of Lipid Research – Vol 52 – Sept 25, 2011
Clinical Trial: April 2010 to Jan 2011 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],JAMA – Nov16, 2011 – Vol 306 – N°19
Torcetrapib (Pfizer) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Journal of Lipid Research – Vol 52 – Sept 25, 2011
Study Design RANDOMIZATION Monotherapy Combination with statins Evacetrapib 100mg N = 398 PLACEBO   n = 38 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Clinic Visits and Laboratory Tests ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],JAMA – Nov16, 2011 – Vol 306 – N°19
Monotherapy Average lipid levels at the beginning:  LDL-C: 144.3mg/dL   HDL-C: 55.1 mg/dL   TG : 121.3 mg/dL  JAMA – Nov16, 2011 – Vol 306 – N°19 . . . .
Combination with statin therapy JAMA – Nov16, 2011 – Vol 306 – N°19 . . . .
Results ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],JAMA – Nov16, 2011 – Vol 306 – N°19
Safety Data JAMA – Nov16, 2011 – Vol 306 – N°19
Adverse Events ,[object Object],[object Object],[object Object],[object Object],JAMA – Nov16, 2011 – Vol 306 – N°19
CONCLUSION (1)  ,[object Object],[object Object],[object Object],[object Object],[object Object],JAMA – Nov16, 2011 – Vol 306 – N°19
CONCLUSION (2) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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Evacetrapib

Editor's Notes

  1. Journal American Medical Association
  2. Pré béta HDL naissante contient ApoA1 et s’enrichit en CE pour maturer et devenir alpha HDL qui s’enrichit encore en CE. La CETP agit ensuite pour échanger CE contre TG avec LDL et VLDL. Le HDL s’appauvrit en CE alors que les LDL et VLDL s’en enrichissent.
  3. Buffer = Tampon
  4. Because mice doesn’t possess CETP activity Because mouse HDL-C particules are not good substrates for human CETP
  5. Potent = Puissant, efficace
  6. Nombre de facteurs de risque variant selon la concentration en LDL-C Hypertension ifi systolic blood pressure sup à 140 mm Hg ou diastolic blood pressure sup à 90 mm Hg … = uncontrolled diabete, significant liver, kidney, cardiac or neuromuscular disease
  7. Blood pressure: Standard automated blood pressure device Lipid profiles: enzymatic assay CRP: immunonephelometry CETP mass: enzyme-linked immunosorbent assay and activity: fluorometric assay La CRP favoriserait le dvpt des plaques athéromateuses ., témoigne de la présence de nbreux élts inflam au sein de la plaque , favorisant sa rupture. dosage de la CRP comme marqueur précoce de l'athérosclérose
  8. Apo E: a previous study demonstrated that ApoE enrichment of HLD-C was associated with an increase in cholesterol efflux wich can involve hightly complex pathway
  9. Assessment = estimation
  10. Stakes = enjeu