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De-risking the development programs of CETP inhibitors after the torcetrapib failure: Structural & functional imaging
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Overview
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Modalities for atherosclerosis imaging
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Imaging the vessel wall in atherosclerosis
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Atherosclerosis regression on statins – wall imaging with MRI
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Plaque composition analysis
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ASTEROID – Potential for plaque regression with IVUS
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IVUS – pooled data suggests regression “tipping point”
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HDL-cholesterol relationship persists in patients treated with statins
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Effect of nicotinic acid on atherosclerosis progression
when added to statin therapy
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Carotid plaque imaging – multi-contrast MRI
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Vascular FUNCTION – aortic pulse wave velocity and compliance
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Brachial artery flow-mediated vasodilatation
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Patient flow
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Effect of nicotinic acid on lipoproteins
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Effect of nicotinic acid on atherosclerosis progression
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Lipoproteins in relation to changes in vessel wall area
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18FDG-PET response to 3 months statin treatment
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18FDG PET signal correlates with macrophage content
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18FDG-PET – plaque measurement parameters
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De-risking ‘challenges’ for imaging
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“Failure of Torcetrapib”
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“Failure of Torcetrapib”
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dal-PLAQUE
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Dal-PLAQUE rationale
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Dal-PLAQUE
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Dal-PLAQUE: design
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Dal-PLAQUE: inclusion
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Dal-PLAQUE: end points
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Dal-PLAQUE: baseline characteristics
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Dal-PLAQUE: baseline characteristics
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Dal-PLAQUE: MRI (24 months) and PET (6 months) outcomes
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Dal-PLAQUE: MRI (24 months): change in total vessel area
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Dal-PLAQUE: MRI (24 months): change in total vessel area
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Dal-PLAQUE: PET-CT (6 months): change in target to background ratio in most diseased segment
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Dal-PLAQUE: PET-CT (6 months): change in target to background ratio in most diseased segment
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Dal-PLAQUE: PET-CT (6 months): change in target to background ratio in most diseased segment by HDL-c tertile
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Dal-PLAQUE: effect on plasma lipids
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Dal-PLAQUE: effect on inflammatory markers
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Dal-PLAQUE: “safety” variables
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Dal-PLAQUE: summary
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Conclusions
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Conclusions
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Prof. Robin Choudhury
Choudhury (PPTX 5.4MB)
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