scholarly journals Effects of the Oral Direct Thrombin Inhibitor Ximelagatran on P-Selectin Expression and Thrombin Generation in Atrial Fibrillation

2003 ◽  
Vol 33 (2) ◽  
pp. 68-74 ◽  
Author(s):  
Michael Wolzt ◽  
Stig L. Boström ◽  
Mia Svensson ◽  
Karin Wåhlander ◽  
Margaretha Grind ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Thrombin Generation ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Oral Direct Thrombin Inhibitor

Inhibition of Thrombin Generation by the Oral Direct Thrombin Inhibitor Ximelagatran in Shed Blood from Healthy Male Subjects

2002 ◽  
Vol 87 (02) ◽  
pp. 300-305 ◽  
Author(s):  
Ulf Eriksson ◽  
Christer Mattsson ◽  
Michael Wolzt ◽  
Lars Frison ◽  
Gunnar Fager ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Active Form ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Healthy Male ◽  
Oral Direct Thrombin Inhibitor ◽  
Shed Blood ◽  
Dose Levels ◽  
Male Subjects ◽  
Control Water

SummaryXimelagatran, an oral direct thrombin inhibitor, whose active form is melagatran, was studied using a model of thrombin generation in humans. Healthy male volunteers (18 per group) received ximelagatran (60 mg p.o.), dalteparin (120 IU/kg s.c.) or a control (water p.o.). Shed blood, collected after incision of the forearm with standardised bleeding time devices at pre-dose, and at 2, 4 and 10 h post-dosing, was analysed for markers of thrombin generation. Statistically significant reductions (p < 0.05) in levels of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) in shed blood were detected at 2 and 4 h post-dosing in both the ximelagatran and dalteparin groups. Shed blood F1+2 and TAT levels had returned to pre-dose levels at 10 h post-dosing. Using a shed blood model, we demonstrate that the reversible thrombin inhibitor melagatran and, therefore, oral administration of ximelagatran, inhibits thrombin generation in humans after acute activation of coagulation.

scholarly journals Exposure-response for biomarkers of anticoagulant effects by the oral direct thrombin inhibitor AZD0837 in patients with atrial fibrillation

2015 ◽  
Vol 80 (6) ◽  
pp. 1362-1373 ◽  
Author(s):  
Gregory Y. H. Lip ◽  
Lars H. Rasmussen ◽  
S. Bertil Olsson ◽  
Eva Jensen ◽  
Bengt Hamrén ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Oral Direct Thrombin Inhibitor ◽  
Exposure Response

scholarly journals Effect of Ximelagatran and Warfarin on Stroke Subtypes in Atrial Fibrillation

2008 ◽  
Vol 35 (2) ◽  
pp. 160-165 ◽  
Author(s):  
Jeanne S. Teitelbaum ◽  
Rüdiger von Kummer ◽  
Knut Gjesdal ◽  
Arni Kristinsson ◽  
Georg Gahn ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
International Normalized Ratio ◽  
Direct Thrombin Inhibitor ◽  
Fixed Dose ◽  
Thrombin Inhibitor ◽  
Stroke Rate ◽  
Stroke Subtype ◽  
Oral Direct Thrombin Inhibitor ◽  
Stroke Outcomes ◽  
Poor Outcome

ABSTRACTBackground and Purpose:The most common stroke subtype among atrial fibrillation (AF) patients not receiving anticoagulants is cardioembolic. In the SPORTIF III and V trials, the oral direct thrombin inhibitor ximelagatran was as effective as warfarin in reducing the risk of stroke in patients with nonvalvular AF. We assessed any differential effect of warfarin versus ximelagatran on the risk and outcome of cardioembolic and noncardioembolic stroke.Methods:7329 patients with AF and ≥1 risk factors for stroke were randomized to treatment with warfarin (target international normalized ratio 2.0-3.0) or fixed-dose ximelagatran. Strokes were classified into specific subtypes. Therapeutic effect of warfarin and ximelagatran, adverse events, and stroke outcomes were assessed according to stroke subtype.Results:The annual stroke rate was low for both cardioembolic (ximelagatran, 0.39%; warfarin, 0.47%) and noncardioembolic stroke (ximelagatran, 0.57%; warfarin, 0.37%). In ischemic strokes, 33.9% (ximelagatran) and 34.3% (warfarin) had strokes of presumed cardioembolic origin. When fatal stroke, disabling stroke, myocardial infarction, and death from any cause were combined as poor outcome, patients with cardioembolic strokes had the highest rate of poor outcome (40%) but this was non- significant.Conclusions:In SPORTIF III and V the efficacy of warfarin and ximelagatran were similar for prevention of cardioembolic and noncardioembolic strokes. Overall outcome tended to be worse following cardioembolic stroke. Ximelagatran has been withdrawn from the market due to hepatic side effects, but similar compounds are presently being studied.

Sign in / Sign up

Export Citation Format

Share Document