title: Potent low dose platelet inhibitory effects of clopidogrel and aspirin on coronary thrombus formation in an animal model of acute unstable angina.
abstract: Application of clopidogrel before percutaneous coronary intervention in patients with acute coronary syndrome reduces the risk of cardiac events. Clopidogrel administration before surgery increases bleeding complications after CABG. Therefore,the antithrombotic effect of the low-dose combination of clopidogrel and aspirin was investigated in an in vivo pig model of coronary artery thrombus formation with cyclic flow reductions. The platelet inhibitory effect was determined by platelet aggregation and CFR, according to the methodology described by Folts. CFR were initiated by endothelial damage and placement of a constrictor around the LAD. 30 min after CFR were established, clopidogrel (0. I mg/kg or 5 mg/kg), aspirin (I mg/kg or 7 mg/kg) or LDC (0. I mg/kg clopidogrel and I mg/kg aspirin) were administered orally. CFR-frequency was determined for further 240 min.CFR-frequency (CFR/30 min) was significantly reduced at 60 min in response to aspirin (7 mg/kg, -48%, p<0.05), and at 120 min in response to clopidogrel (5 mg/kg,-65%, p<0.05) but not at low doses of either compound. In contrast, LDC of clopidogrel (0. I mg/kg) plus aspirin (I mg/kg) resulted in a complete and rapid abrogation of CFR at 90 min (-70%, p<0.05 y. Furthermore, LDC led to reduction of platelet aggregation when CFR-frequency was already significantly decreased. In contrast, high dose groups presented a significant reduction of platelet aggregation prior to CFR-frequency decrease. Low dose combination of clopidogrel plus aspirin demonstrates a potent over additive anti-thrombotic effect in vivo with a significant reduction in thrombus formation early after drug application. The effect occurs before inhibition of platelet aggregation is detectable.
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany. bier.bach@gmx.de
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bierbach
authors.forename: Georg
authors.initials: G
authors.lastname: Horstick
authors.forename: Oliver
authors.initials: O
authors.lastname: Berg
authors.forename: Axel
authors.initials: A
authors.lastname: Heimann
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.forename: Christian-Friedrich
authors.initials: CF
authors.lastname: Vahl
authors.forename: Oliver
authors.initials: O
authors.lastname: Kempski
authors.forename: Harald
authors.initials: H
authors.lastname: Darius
mesh_terms: D000208:Acute Disease; D000789:Angina, Unstable / Q000150:complications / Q000188:drug therapy*; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000517:prevention & control; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D013552:Swine; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin