Abciximab reduces monocyte tissue factor in carotid angioplasty and stenting.
OBJECTIVE
Abciximab, a nonselective glycoprotein IIb/IIIa inhibitor, was shown to reduce peri-interventional stroke rate in carotid stenting. We evaluated the effect of adjunct abciximab therapy on monocyte-platelet cross talk and neurological deficit in unprotected carotid stenting and compared its efficacy with distal filter protection.


METHODS
Fifty patients were randomized to either standard antithrombotic therapy (n=30) consisting of aspirin, clopidogrel, and heparin or adjunct bolus (0.25 mg/kg) and 12-hour infusion (0.125 microg x kg(-1) x min(-1)) of abciximab (n=20). A third cohort of patients was stented with filter protection (n=30). Monocyte-platelet aggregate formation and monocyte tissue factor expression were determined by whole blood flow cytometry, and F1.2 generation and soluble CD40 ligand (sCD40L) were determined by immunoassay.


RESULTS
The incidence of peri-interventional ischemic episodes (23% versus 10%; P=0.2) and the number of de novo ischemic lesions detected by diffusion-weighted MRI (47% versus 30%; P=0.17) were not significantly different between standard antithrombotic therapy and adjunct abciximab but were reduced with filter protection (P=0.023). However, the number of transient ischemic attacks was lower (P=0.05) and the National Institutes of Health Stroke Score rapidly decreased in patients with adjunct abciximab. This clinical improvement was paralleled by a reduction in the postinterventional percentage of activated monocyte-platelet aggregates (CD62P+/CD14+; P=0.018) and the number of tissue factor-positive monocytes (TF+/CD14+; P=0.005). Both abciximab and filter protection suppressed F1.2 generation and significantly reduced sCD40L.


CONCLUSIONS
Abciximab limits thrombus propagation and thrombus stabilization after carotid stenting by reducing monocyte-platelet cross talk and sCD40L. Although abciximab seems inferior to filter devices in peri-interventional cerebral protection, it may be considered in patients who do not allow placement of protection devices.
Kopp
Christoph W
CW
Second Department of Medicine, Division of Angiology, University of Vienna Medical School, General Hospital, AKH, Waehringer Guertel 18-20, 1090 Vienna, Austria. christoph.kopp@univie.ac.at
Steiner
Sabine
S
Nasel
Christian
C
Seidinger
Daniela
D
Mlekusch
Irene
I
Lang
Wilfried
W
Bartok
Andrea
A
Ahmadi
Ramazanali
R
Minar
Erich
E
D000077284:Abciximab; D000368:Aged; D017130:Angioplasty / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control; D016893:Carotid Stenosis / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D002449:Cell Aggregation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D005374:Filtration; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D015607:Stents / Q000009:adverse effects; D013925:Thromboplastin / Q000378:metabolism*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013925:Thromboplastin; D000077284:Abciximab