Antithrombotic assessment of the effects of combination therapy with the anticoagulants efegatran and heparin and the glycoprotein IIb-IIIa platelet receptor antagonist 7E3 in a canine model of coronary artery thrombosis.

Abstract

BACKGROUND:

There is a paucity of data regarding the antithrombotic pharmacology of the drug-drug interactions between the newer anticoagulant and antiplatelet agents. In this investigation, we have studied the antithrombotic effects of combinations of minimum effective doses of the glycoprotein IIb-IIIa receptor antagonist 7E3 [murine F(ab')2] with both heparin and the novel tripeptide arginal antithrombin efegatran (LY294468) in a canine model of coronary artery thrombosis.

METHODS AND RESULTS:

Thrombogenesis was initiated by electrolytic injury of the intimal surface of the left circumflex coronary artery. The groups studied were efegatran (0.25 mg . kg-1. h-1), heparin (80 U/kg, single injection, plus 30 U . kg-1. h-1), 7E3 (0.4 mg/kg, single injection), 7E3+efegatran, and 7E3+heparin. The combination of 7E3+efegatran was found to maintain better vessel patency (P < .05) at the end of the experiment (4 of 5 vessels) than all other groups (0 of 5, 0 of 4, 1 of 6, 2 of 7, and 1 of 6 for the vehicle-, heparin-, 7E3-, efegatran-, and 7E3+heparin-treated groups, respectively). Bleeding times were increased (P < .05) in both the 7E3+heparin group (fourfold) and the 7E3+efegatran group (threefold). 7E3 alone and both combination treatments produced significant reductions in ADP, arachidonic acid, and thrombin-induced platelet aggregation, whereas efegatran and heparin abolished only thrombin-induced aggregation.

CONCLUSIONS:

The present investigation demonstrates that combination therapy with minimum effective doses of 7E3+efegatran provided enhanced antithrombotic efficacy compared with 7E3+heparin in this model of thrombosis.

• Authors: T J Shetler, V G Crowe, B D Bailey, C V Jackson
• Journal: Circulation (Circulation) Vol. 94 Issue 7 Pg. 1719-25 (Oct 01 1996) ISSN: 0009-7322 [Print] United States
• PMID: 8840866 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Fibrinolytic Agents
• Immunoglobulin Fab Fragments
• Oligopeptides
• Platelet Aggregation Inhibitors
• Platelet Glycoprotein GPIIb-IIIa Complex
• Heparin
• efegatran
• Abciximab

Topics

• Abciximab
• Animals
• Antibodies, Monoclonal (therapeutic use)
• Bleeding Time
• Blood Pressure (drug effects)
• Coronary Thrombosis (blood, drug therapy, physiopathology)
• Dogs
• Drug Therapy, Combination
• Female
• Fibrinolytic Agents (therapeutic use)
• Heart Rate (drug effects)
• Heparin (therapeutic use)
• Immunoglobulin Fab Fragments (therapeutic use)
• Male
• Oligopeptides (therapeutic use)
• Platelet Aggregation Inhibitors (therapeutic use)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors)