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

Thrombosis and Haemostasis
Karin WåhlanderAnders Bylock

Abstract

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 after 2 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, r...Continue Reading

Citations

Apr 28, 2007·Expert Opinion on Investigational Drugs·Marc Husmann, Matthias Barton
Aug 21, 2009·Journal of Thrombosis and Haemostasis : JTH·R ChelliahD E Newby
Mar 9, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Andrew J LuckingDavid E Newby
Oct 28, 2008·European Heart Journal·Andrew J LuckingDavid E Newby
Dec 12, 2012·British Journal of Clinical Pharmacology·Ghazaleh GouyaGottfried Heinz
Jul 12, 2012·European Journal of Clinical Pharmacology·Sebastian HärtterJeffrey Friedman
Dec 23, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Simon J WilsonDavid E Newby

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