Antithrombotic effects of abciximab.
The observation that platelet-platelet interaction and thrombosis are ultimately regulated by the glycoprotein (GP) IIb/IIIa receptor complex, triggered the development of agents capable of interfering with this platelet receptor complex. Several large clinical trials have demonstrated the effectiveness of this class of agents. The first of these agents to show beneficial effects after coronary interventions was the mouse/human chimeric Fab fragment antibody c7E3 (abciximab; ReoPro). This study analyzes whether the addition of heparin to the GP IIb/IIIa antagonist abciximab would enhance the antithrombotic effect. Blood drawn directly from patients on aspirin who underwent interventional procedures perfused an ex vivo perfusion chamber containing a severely injured arterial wall at local rheologic conditions of a mildly stenosed coronary artery. Blood was perfused directly from patients at baseline and following administration of heparin, abciximab, or both. The antithrombotic effects of the 3 treatments were assessed by reduction of the thrombus formation on the perfused specimens. Thrombus formation at baseline was not significantly modified by the administration of heparin (13,897 +/- 1,316 vs 11,917 +/- 1,519 microm(2)). Abciximab produced a 58% reduction in thrombus formation (11,631 +/- 861 vs 4, 925 +/- 585 microm(2); p <0.001). The addition of heparin to abciximab did not further reduce thrombus area versus abciximab alone (5,651 +/- 581 vs 4,925 +/- 585 microm(2)). Thus, our data show that abciximab dramatically decreases mural thrombus formation and that combining heparin with abciximab did not add any additional antithrombotic effect to abciximab alone.
Hayes
R
R
Zena and Michael A. Wiener Cardiovascular Institute, New York, New York 10029, USA.
Chesebro
J H
JH
Fuster
V
V
Dangas
G
G
Fallon
J T
JT
Sharma
S K
SK
Coller
B S
BS
Badimon
L
L
Marmur
J D
JD
Badimon
J J
JJ
D000077284:Abciximab; D000789:Angina, Unstable / Q000188:drug therapy*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use*; D001241:Aspirin / Q000097:blood / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000097:blood / Q000627:therapeutic use; D006331:Heart Diseases / Q000517:prevention & control*; D006493:Heparin / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000097:blood / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000627:therapeutic use*; D013927:Thrombosis / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D006493:Heparin; D001241:Aspirin; D000077284:Abciximab