1 / 15

Daniel J. Rader, MD University of Pennsylvania

Discussant: Lipid-Modulating Effects of Evacetrapib, a Novel CETP Inhibitor AHA Scientific Sessions November 15, 2011. Daniel J. Rader, MD University of Pennsylvania. Lipoproteins and Atherosclerosis. ?. A-I. TG, CE. B. CE. VLDL, LDL, remnants, Lp(a). HDL. The HDL-C hypothesis.

tilly
Télécharger la présentation

Daniel J. Rader, MD University of Pennsylvania

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Discussant:Lipid-Modulating Effects of Evacetrapib, a Novel CETP InhibitorAHA Scientific Sessions November 15, 2011 Daniel J. Rader, MD University of Pennsylvania

  2. Lipoproteins and Atherosclerosis ? A-I TG, CE B CE VLDL, LDL, remnants, Lp(a) HDL

  3. The HDL-C hypothesis Raising plasma HDL-C levels will reduce CV events.

  4. Anti-atherogenic HDL functions HDL Anti-oxidant NO-promoting Anti-inflammatory Anti-thrombotic Cholesterol efflux and reverse cholesterol transport

  5. Reverse Cholesterol Transport Bile ABCG1 A-I A-I FC CE FC LCAT FC CE ABCA1 SR-BI Macrophage Liver

  6. Cholesteryl ester transfer protein (CETP) transfers cholesterol out of HDL Bile ABCG1 A-I A-I FC CE FC LCAT FC CE ABCA1 SR-BI Macrophage Liver CETP LDLR CE B TG VLDL/LDL

  7. CETP Deficiency is Associated with Markedly Increased HDL-C Levels A-I Bile ABCG1 FC A-I FC CE CE LCAT FC ABCA1 SR-BI Macrophage Liver X CETP LDLR CE B TG VLDL/LDL

  8. CETP Inhibition as a Novel Strategy to Raise HDL Cholesterol Bile A-I A-I FC CE FC LCAT FC CE ABCA1 SR-BI Macrophage Liver X CETP LDLR CETP inhibitor CE B TG VLDL/LDL

  9. CETP Inhibitors o o o CETP Evacetrapib Torcetrapib Anacetrapib Dalcetrapib Slide courtesy of Dr Bryan Brewer

  10. Lipid efficacy of CETP inhibitors(% change from baseline) Adapted from Cannon C, JAMA 306:2154; 2011

  11. dal-OUTCOMES Dalcetrapib 600 mg 15,600 patients 4-12 weeks after an index ACS event Statin therapy to optimal LDL-C level Placebo 2.5-year follow-up Primary End Point CHD death, non-fatal MI, atherothrombotic stroke, unstable angina requiring hospitalization or resuscitated cardiac arrest Schwartz et al. Am Heart J. 2009;158:896-901.

  12. 30,000 patients with occlusive arterial disease in North America, Europe and Asia Background LDL-lowering with atorvastatin Randomized to anacetrapib 100 mg vs. placebo Scheduled follow-up: 4 years Primary outcome: coronary death, myocardial infarction or coronary revascularization www.revealtrial.org

  13. CETP inhibitor outcome trials

  14. CETP inhibitor outcome trials

More Related