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Published byRory Edgell Modified over 8 years ago
Stents Are Not Enough: Statins Keith Channon Department of Cardiovascular Medicine University of Oxford John Radcliffe Hospital, Oxford
5.07 mm 2 5.18 mm 2 Plaque Remodelling in Angiographically Normal Artery Preservation of Lumen Area
Stable Plaque Unstable Plaque (Erosion, Rupture) Plaque Growth
Plaque Biology = Clinical Events –T lymphocyte – Macrophage foam cell (tissue factor + ) – “Activated” intimal SMC (HLA-DR + ) –Normal medial SMC “Stable” plaque “Vulnerable” plaque Lumen area of detail Lumen Lipid core Lipid core
Cellular Mechanisms of Plaque Stability
IVUS Assessment of Plaque Stability Thick Fibrous CapThin Fibrous Cap
Acute vs. Chronic Coronary Syndromes: Plaque Composition Lipid Content >40%Macrophages (%)Smooth Muscle (%) Stable Unstable
Angiographic Stenosis in Infarct-Related Artery Most are not severely stenosed
Additional Unstable Plaques Beyond the Culprit Lesion 27 patients with ACS. Angio + 3 vessel IVUS
Plaque Biology, Stenosis and Risk: The Paradox for PCI
Plaque Biology, Stenosis and Risk Stents are Not Enough ? Using current technology, Stenting alone cannot treat all high risk lesions Stenting alone does nothing to alter disease biology or natural history …….Statins ?
LDL Cholesterol Lowering by Statins
Acetyl-CoA HMG-CoA Mevalonic Acid Cholesterol VLDL LDL Cholesterol Metabolism – Regulation by HMG CoA Reductase HMG CoA Reductase
Acetyl-CoA HMG-CoA Mevalonic Acid Cholesterol VLDL LDL Cholesterol Metabolism – Regulation by HMG CoA Reductase Statins
LDL Acetyl-CoA HMG-CoA Mevalonic Acid VLDL LDL Cholesterol Metabolism – Regulation by HMG CoA Reductase Statins Cholesterol LDL
Statins and Cholesterol Synthesis: Effects on Cell Signalling through Isoprenoids Acetyl CoA HMG CoA Mevalonate Cholesterol HMG CoA Reductase Isoprenoid Derivatives Modification of Cell Signalling Proteins e.g. G-Proteins Rho, Rac ‘Pleiotrophic’ Effects on Vascular Cells: Gene Regulation Cell Proliferation eNOS Expression Inflammation Apoptosis Stem & Progenitor Cells Statins
STATINS CRP Endothelial Function Cytokines
TVA 15.47 mm 2 Lumen 5.51 mm 2 Plaque = 9.96 mm 2 18 Months N=522 paired IVUS P=0.02 REVERSAL : Reductions in LDL, Plaque Volume and CRP PRAVASTATIN 40 mg ATORVASTATIN 80 mg LDL-C (%) - 25 % - 46 % CRP (%) - 5 % - 36 % Change in Plaque Vol (%) 0 1.02.03.0
Heart Protection Study – Major Vascular Events
80 mg LIPS : Benefits of Statin Following PCI
Statin Therapy and Outcome after PCI: Cleveland Clinic n=1552 Circulation 2003; 107;1750-6 n=5052 Circulation 2002; 105;691-6
AVERT : Atorvastatin Versus Revascularization Treatments Pitt B et al. N Engl J Med 1999;341:170-6 Randomised to Atorvastatin 80 mg vs. PCI + Usual Care
AVERT : Time to First Ischaemic Event
AVERT : Major Exclusion Criteria
AVERT : Baseline Characteristics
AVERT : Ischaemic Events at 18 Months
Why are Stents not Enough ? Stents treat lesions that are selected on luminal stenosis Plaque events are determined more by plaque biology, rather than stenosis Coronary disease is diffuse and progressive PCI at discrete sites does not alter disease burden or progression
Why Statins ? Statins directly alter CAD natural history through lipid lowering and other direct cellular effects Effects on mortality and morbidity in very large studies in primary and secondary prevention, including PCI High Dose, more potent newer statins can achieve plaque regression and stabilisation Stenting symptomatic stenoses combined with high-dose statin therapy is currently best CAD management strategy
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