Antithrombotic effects of ximelagatran plus acetylsalicylic acid (ASA) and clopidogrel plus ASA in a human ex vivo arterial thrombosis model

Karin Wåhlander; Maria Eriksson-Lepkowska; Per Nyström; Ulf G. Eriksson; Troy C. Sarich; Juan J. Badimon; Inge Kalies; Margareta Elg; Anders Bylock

doi:10.1160/TH05-10-0664

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(03): 447-453
DOI: 10.1160/TH05-10-0664

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Antithrombotic effects of ximelagatran plus acetylsalicylic acid (ASA) and clopidogrel plus ASA in a human ex vivo arterial thrombosis model

Authors

Karin Wåhlander

¹AstraZeneca R&D Mölndal, Mölndal, Sweden
Maria Eriksson-Lepkowska

¹AstraZeneca R&D Mölndal, Mölndal, Sweden
Per Nyström

¹AstraZeneca R&D Mölndal, Mölndal, Sweden
Ulf G. Eriksson

¹AstraZeneca R&D Mölndal, Mölndal, Sweden
Troy C. Sarich

²AstraZeneca LP, Wilmington, Delaware, USA
Juan J. Badimon

³Cardiovascular Institute, Mount Sinai School of Medicine, New York, USA
Inge Kalies

¹AstraZeneca R&D Mölndal, Mölndal, Sweden
Margareta Elg

¹AstraZeneca R&D Mölndal, Mölndal, Sweden
Anders Bylock

¹AstraZeneca R&D Mölndal, Mölndal, Sweden

Abstract

Summary

It was the objective of this study to compare the antithrombotic effects and bleeding profiles of the oral direct thrombin inhibitor ximelagatran, an anticoagulant, and the antiplatelet agent clopidogrel on top of steady-state acetylsalicylic acid (ASA) in a human arterial thrombosis model. Healthy male volunteers (n=62) received ASA (160 mg once daily),plus either clopidogrel for 6 days (loading dose 300 mg, then 75 mg once daily), or a single dose of ximelagatran (36 or 72 mg) on Day 6. Changes in total thrombus area (TTA) under low shear rate (LSR; 212 s-1) and high shear rate (HSR; 1690 s-1) conditions were measured, using the ex vivo Badimon perfusion chamber model pre-dose and 2 and 5 hours after dosing on Day 6, and capillary bleeding times (CBT) were determined. Ximelagatran plus ASA significantly reduced TTA under LSR and HSR, compared with ASA alone. Ximelagatran plus ASA reduced TTA more than clopidogrel plus ASA under LSR after2 hours (36 mg, P=0.0011; 72 mg, P<0.0001) and 5 hours (72 mg, P=0.0057), and under HSR after 2 and 5 hours (72 mg, P<0.05). Compared with ASA alone, CBT was markedly prolonged by clopidogrel plus ASA (ratio 6.4; P<0.0001) but only slightly by ximelagatran plus ASA (72 mg ximelagatran,ratio 1.4;P=0.0010).Both drug combinations were well tolerated. Oral ximelagatran plus ASA has a greater antithrombotic effect in this human ex vivo thrombosis model and a less prounounced prolongation of bleeding time than clopidogrel plus ASA.

Keywords

Clinical trials - oral anticoagulants - coagulation inhibitors - thrombin

Full Text

References

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