The antithrombotic effect of melagatran in combination with clopidogrel and/or aspirin (carotid artery primary thrombosis study).
Melagatran with aspirin and/or clopidogrel was evaluated for prevention of arterial thrombosis in a model of vessel wall injury. Thirty-five dogs were randomized to receive placebo (n=14), aspirin (7 to 8 mg/kg, p.o. q12 h for three doses with the last dose administered 12 hours before surgery, n=7), clopidogrel (1 mg/kg p.o. QDx3, n=7), or aspirin+clopidogrel (n=7). The right carotid artery (RCA) was the control vessel, whereas the left carotid artery (LCA) was subjected to injury after administration of Melagatran (0.033 mg/kg i.v.+0.1 mg/kg/h). Clopidogrel, but not aspirin pretreatment, increased time (135.6+/-13.5 vs. 116.1+/-27.8 minutes) to RCA thrombosis versus placebo (88.1+/-10.5 minutes). Melagatran prolonged time to occlusion (min) in the LCA (192.4+/-10.9) versus the placebo-treated RCA (88.1+/-10.5). Addition of Melagatran plus aspirin or clopidogrel prevented formation of occlusive thrombosis, in all LCAs. A two-fold increase in tongue bleeding time was observed after aspirin+Melagatran (178.6+/-14.7 to 347.1+/-87.3 seconds) or clopidogrel+Melagatran (279.9+/-97.3 to 437.1+/-142.5 seconds). However, the combination of aspirin and clopidogrel prevented occlusive thrombosis in the RCA and the subsequent addition of Melagatran did not further increase bleeding time. The combination of Melagatran+aspirin or clopidogrel can reduce formation of occlusive arterial thrombosis without eliciting a significant increase in bleeding-time.
Hong
Ting-Ting
TT
University of Michigan Medical School, Ann Arbor, MI 48109-0632, USA.
Huang
Jinbao
J
Driscoll
Edward
E
Lucchesi
Benedict R
BR
D000818:Animals; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D001384:Azetidines / Q000494:pharmacology* / Q000627:therapeutic use; D001596:Benzylamines / Q000494:pharmacology* / Q000627:therapeutic use; D001760:Bleeding Time; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002341:Carotid Artery Thrombosis / Q000188:drug therapy* / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D000077144:Clopidogrel; D004195:Disease Models, Animal; D004285:Dogs; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014059:Tongue / Q000098:blood supply; D014654:Vascular Patency / Q000187:drug effects
D001384:Azetidines; D001596:Benzylamines; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; C109573:melagatran; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin