Clopidogrel pretreatment abolishes increase of PAI-1 after coronary stent implantation.
BACKGROUND
Plasminogen activator inhibitor-1 (PAI-1) has been shown to increase after percutaneous coronary intervention (PCI). Whether activated platelets, local trauma with activation of resident vascular cells or the acute phase response is the source of this PAI-1 increase is not well defined. Therefore we examined whether intensive platelet inhibition may modulate PAI-1 levels or whether the PAI-1 increase is associated with the acute phase protein C-reactive protein (CRP).


METHODS
We included 51 patients with stable angina who underwent elective PCI with stent implantation. At the time of study, routine pretreatment with clopidogrel before PCI was not standard of care, but left to the discretion of the referring cardiologist. We matched 17 patients with stable angina that were not pretreated with clopidogrel but received a loading dose of 300 mg immediately after stent implantation according age, sex and smoking with 34 patients that received clopidogrel at least 12 to 24 hours before PCI. Blood samples for measurement of PAI-1, t-PA and CRP were taken directly before and 24 hours after the procedure.


RESULTS
PAI-1 and t-PA active antigen plasma levels before PCI were not different in patients with and without clopidogrel pretreatment. Whereas PCI induced a significant increase of PAI-1 levels in patients without pretreatment (p<0.05), the procedure had no effect on PAI-1 active antigen in patients pretreated with clopidogrel. This resulted in significant lower PAI-1 plasma levels 24 hours after PCI in patients with pretreatment (p<0.05). CRP was not associated with pre- or postprocedural PAI-1 levels.


CONCLUSIONS
Clopidogrel pretreatment completely abolishes the increase of PAI-1 active antigen after coronary stent implantation. This suggests that peri-procedural platelet activation might play a major role for the increase of PAI-1 after PCI thus increasing the risk of acute and subacute thrombus formation based on a reduced endogenous fibrinolytic system.
Katsaros
Katharina M
KM
Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Kastl
Stefan P
SP
Huber
Kurt
K
Zorn
Gerlinde
G
Maurer
Gerald
G
Glogar
Dietmar
D
Wojta
Johann
J
Christ
Günter
G
Speidl
Walter S
WS
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D002097:C-Reactive Protein / Q000032:analysis; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000097:blood
D017395:Plasminogen Activator Inhibitor 1; D010975:Platelet Aggregation Inhibitors; D002097:C-Reactive Protein; D000077144:Clopidogrel; D010959:Tissue Plasminogen Activator; D013988:Ticlopidine