• Stabilization of destabilized (disrupted and/or thrombotic plaque) • Stabilization of vulnerable (prone to destabilization) plaque • Stabilization through the following processes Thrombogenicity in blood Vessel passivation Traditional concepts of stabilization: Plaque lipid and thrombogenicity Inflammation Endothelial function • Stabilization to prevent – In-hospital events – Intermediate and long-term events VBWG New multifaceted approach to plaque stabilization Adapted from Ambrose JA, Martino EE. Circulation. 2002;105:2000-4.
Statins LDL oxLDL Lymphocyte 3 1 NO Inactivation 2 LFA-1 Monocyte – NO Selective block – HMG-CoA reductase activity ICAM-1 – Reduced adhesion NO production Geranylgeranyl PP Farnesyl PP – + + Reduced prenylation Rho protein Increased stability of mRNA Increased transcription NOS mRNA Decreased activation NF-kB Endothelial cell VBWG Anti-inflammatory actions of statins LFA-1 = lymphocyte function-associated antigen-1 Sposito AC, Chapman J. ATVB. 2002;22:1524-34.
VBWG “At this juncture, there is no clear evidence that clinicians should choose statins on the basis of CYP3A4 metabolism when clopidogrel coadministration is required.”