New multifaceted approach to plaque stabilization

Adapted from Ambrose JA, Martino EE. Circulation. 2002;105:2000-4.

VBWG

• 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

• Stabilization of destabilized (disrupted and/or thrombotic plaque)

• Stabilization of vulnerable (prone to destabilization) plaque

Anti-inflammatory actions of statins

Sposito AC, Chapman J. ATVB. 2002;22:1524-34.LFA-1 = lymphocyte function-associated antigen-1

3

–

LDL oxLDL

NO Inactivation

NO Monocyte

Reducedadhesion

1

–

Lymphocyte

LFA-1

Statins

Selectiveblock

2

+

–

–+

NO production

Reduced prenylationRho protein

Geranylgeranyl PPFarnesyl PP

HMG-CoA reductaseactivity

Increased stability of mRNA

Increased transcriptionNOS mRNA

Decreased activationNF-B Endothelial cell

ICAM-1

VBWG

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.”