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Pharmacologic treatment of vulnerable plaque


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SHAPE Society

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Pharmacologic treatment of vulnerable plaque

  1. 1. Pharmacologic Stabilization of Vulnerable Plaque: A Premature Concept?
  2. 2. LDL Ox LDL Infection/inflammation Homocysteine Smoking Endothelial release of MCP-1 NO PGI2 HSPG  tPA Tm ICAM 1 VCAM 1 TSP TNF α IL 1 PAI1 MONOCYTE: Chemo-attraction (MCP 1) Attachment(LFA1, Mac1,etc) Attraction (NFκB) Proliferation (TNF α,MCSF) Secretion of TNF α , IL-1, MCP-1, NO T cell activation (CD 40) Inhibition of SMC metabolism Activation of MMPs Apoptosis of SMC Activation of acid proteases Angiogenesis Diet low in antioxidants Low HDL A-II
  3. 3. Inflammation Coagulation
  4. 4. Pharmacologic Stabilization of Vulnerable Plaque  Anti-inflammatory agents (aspirin, Plavix, etc)  Antiplatelets  Anticoagulants  Antiplatelets  Anti-microbials  Lipid-lowering agents  Antioxidants  Beta blockers  Angiogenesis inhibitors (endostatin, α VEGF)  eNOS inductors
  5. 5. Pharmacologic Stabilization of Vulnerable Plaque, contd.  ACE inhibitors  MMP inhibitors  Vasodilators (amlodipine, TNG)  Apo A1 Milano, HDL  TF inhibitors  CETP inhibitors  Cytokines antagonists (selectins, ICAM, VCAM, NFκB, TGF-ß, MCP-1, TNF-α, PDGF)  Retinoids (retinoic acid, TGF-ß)  Antibodies to CD40 ligand  Cap strengthening (TGF -ß, antibody to IF γ)
  6. 6. Anti-inflammatory Aspirin NSAIDs Cox-2 inhibitors Statins
  7. 7. Triggers of Plaque Rupture Awakening Rx: Aspirin Exercise Anti-adrenergics Anger Timing of Rx Fear (e.g., earthquake) Counseling Sexual activity Sedatives? Fatty meal Anti- depressants? Cocaine, decongestants, marijuana Cold weather Pollution Mondays
  8. 8. Statins Simvastatin Atorvastatin Pravastatin Fluvastatin Lovastatin Cerivastatin Rosuvastatin
  9. 9. Anti-microbials roxithromycin azithromycin ganciclovir oseltamivir zanamivir Future
  10. 10. Antioxidants  α-tocopherol  β-carotene  Vitamin C  Selenium  Flavunoids  Green tea  N-acetyl cycteine  Probucol  Dietary fat reduction  eNOS induction  Statins
  11. 11. Antiplatelets and Antithrombotics Aspirin, Ticlopidine, Clopidogrel Heparin, LMWH GPIIb/IIIa inhibitors Antibodies (Abciximab) Synthetic antagonists (Eptifibatide, Tirofiban) Thrombin Inhibitors (Argatroban,Hirudins)
  12. 12. Texas Heart Institute University of Texas-Houston Center for Vulnerable Plaque Research