Clopidogrel Inhibition of Stent, Graft, and Vascular Thrombogenesis With Antithrombotic Enhancement by Aspirin in Nonhuman Primates
| Autor: | J.-M. Herbert, N. R. F. Chronos, Laurence A. Harker, Andrew B. Kelly, Ulla M. Marzec, Stephen R. Hanson, I. B. Sundell |
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| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Bleeding Time Ticlopidine medicine.medical_treatment Endarterectomy Bleeding time Physiology (medical) Internal medicine Antithrombotic medicine Animals Drug Interactions Platelet Thrombus Hemostasis Aspirin medicine.diagnostic_test Heparin Polyethylene Terephthalates business.industry Stent Thrombosis medicine.disease Clopidogrel Anesthesia Cardiology Stents Cardiology and Cardiovascular Medicine business Platelet Aggregation Inhibitors Papio medicine.drug |
| Zdroj: | Circulation. 98:2461-2469 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | Background —A recent study showed that clopidogrel reduces thrombo-occlusive complications in patients with symptomatic atherosclerosis more effectively than aspirin. Methods and Results —The effects of clopidogrel and aspirin have been compared, singly and in combination, for measurements of 111 In-labeled platelets and 125 I-labeled fibrin deposition in baboon models of arterial thrombosis and related to platelet aggregation and expression of activation epitopes induced by ADP, collagen, and thrombin receptor agonist peptide (TRAP) and to template bleeding times (BTs). Low-dose oral clopidogrel (0.2 mg · kg −1 · d −1 ) produced cumulative (1) intermediate decreases in 111 In-platelet and 125 I-fibrin deposition for segments of prosthetic vascular graft, deployed endovascular metallic stents, and endarterectomized aorta ( P P P P =0.03). High-dose oral clopidogrel (≥2 mg/kg) produced the same effects within 3 hours. The effects of clopidogrel dissipated over 5 to 6 days. Aspirin 10 mg · kg −1 · d −1 alone did not decrease 111 In-platelet and 125 I-fibrin deposition on segments of vascular graft but detectably decreased 111 In-platelet and 125 I-fibrin accumulation on stents ( P P P =0.004). Within 3 hours of aspirin administration, the antithrombotic effects of acute high-dose or chronic low-dose clopidogrel were substantially enhanced, and BTs were modestly prolonged without inhibiting platelet aggregation induced by TRAP ( P Conclusions —Clopidogrel produces irreversible, dose-dependent, intermediate reduction in thrombosis that is substantially enhanced by the addition of aspirin. The effects of combining aspirin and clopidogrel need to be evaluated in patients at risk of vascular thrombosis. |
| Databáze: | OpenAIRE |
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