Safety assessment of new antithrombotic agents: Lessons from the EXTEND study on ximelagatran

Agnelli, Giancarlo; Eriksson, Bengt I.; Cohen, Alexander T.; Bergqvist, David; Dahl, Ola E.; Lassen, Michael R.; Mouret, P; Rosencher, Nadia; Andersson, Magnus; Bylock, Anders; Jensen, Eva C.; Boberg, Barbro

doi:10.1016/j.thromres.2008.02.017

Cited by 81 publications

(65 citation statements)

References 10 publications

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“…This concern led to the development of a study that could evaluate a risk for ximelagatran vs enoxaparin. In this study, the EXTEND trial [58], long term administration of ximelagatran was associated with statistically greater risk for liver toxicity compared to enoxaparin. The fact that this toxicity was observed even after the treatment discontinuance and that ximelagatran was connected with more deaths than enoxaparin led the USA FDA to decline an approval for its use as an anticoagulant [59].…”

Section: Ximelagatran In Venous Thromboembolismmentioning

confidence: 76%

Prevention and Treatment of Venous Thromboembolism and Pulmonary Embolism: The Role of Novel Oral Anticoagulants

Deftereos

Hatzis²,

Kossyvakis³

et al. 2012

CCP

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Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, is the third most common cause of vascular death after myocardial infarction and stroke. Clinicians are often summoned to make challenging decisions for the prevention and treatment of high risk patients with an unpredicted outcome, often relying on data that are less than definitive. During the last decades, heparins (unfractionated and low molecular weight heparins) as well as vitamin K antagonists, such as warfarin, and indirect Xa inhibitors, such as fontaparinux, are the cornerstone for the prevention and treatment of patients with venous thromboembolism. However, the traditionally used anticoagulants have several drawbacks that may limit their efficacy and use in every day clinical practise. The newly developed oral anticoagulants, belonging to the categories of direct thrombin inhibitors (DTIs) and direct Xa inhibitors, have emerged as promising agents with remarkable efficacy, concentrating many parameters of an ideal anticoagulant. Rivaroxaban, dabigatran and apixaban are the most studied agents, while a plethora of others are investigated in clinical trials of different phases and are expected to reach the market in the following years. The purpose of this review is to summarize the so far acquired knowledge on these agents, to report briefly some of their pharmacodynamic and pharmacokinetic properties and to focus on their role in the treatment and prevention of venous thromboembolism.

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Section: Ximelagatran In Venous Thromboembolismmentioning

confidence: 76%

Prevention and Treatment of Venous Thromboembolism and Pulmonary Embolism: The Role of Novel Oral Anticoagulants

Deftereos

Hatzis²,

Kossyvakis³

et al. 2012

CCP

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“…Some anticoagulants have been withdrawn from the market because of their side eff ects on the liver function 18 . Our results showed an increase in AST and ALT levels immediately after the surgery in the patients receiving nadroparin calcium, while in the patients receiving fondaparinux the levels of AST and ALT decreased throughout their hospital stay.…”

Section: Discussionmentioning

confidence: 99%

Influence of Fondaparinux Versus Nadroparin Calcium Thromboprophylaxis on Clinical Parameters Following Total Knee Arthroplasty

Mihaljević¹

2016

acc

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SUMMARY -Fondaparinux has been shown to be as eff ective as low molecular weight heparin in orthopedic surgery, with no cases of heparin induced thrombocytopenia proven until today. Th e main goal of this prospective randomized controlled trial was to defi ne whether thromboprophylaxis in patients with primary osteoarthritis of the knee undergoing total knee arthroplasty (TKA) infl uences clinical parameters in the same manner in patients receiving fondaparinux as in those receiving nadroparin during the fi rst 7 postoperative days. Sixty patients with primary knee osteoarthritis underwent unilateral TKA performed by the same surgeon and were randomized into two groups of 30 patients receiving either fondaparinux or nadroparin thromboprophylaxis. Patients were compared according to the duration of operation, perioperative blood loss, laboratory results and clinical evaluation of the edema during the early postoperative period. No diff erences were found between the groups in the mean duration of surgery, perioperative blood loss, and most of laboratory results. Th e level of urea was signifi cantly lower in the nadroparin group on the fi rst and second postoperative day. No cases of heparin induced thrombocytopenia, deep vein thrombosis or pulmonary embolism were noted during the study. Study results showed both fondaparinux and nadroparin to have the same infl uence on clinical parameters during the fi rst 7 postoperative days in patients undergoing TKA.

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“…On the basis of health concerns ximelagatran did not receive Food and Drug Administration (FDA) approval and it was subsequently withdrawn by AstraZeneca following the EXTEND study because of fear of liver toxicity [5]. The EXTEND study was terminated due to a case of severe acute liver injury just 3 weeks after completion of the 35-day course of treatment.…”

Section: Historical Excursus: Ximelagatranmentioning

confidence: 99%

Direct Thrombin Inhibitors

Shantsila

Lip

2016

Non-Vitamin K Antagonist Oral Anticoagulants

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Safety assessment of new antithrombotic agents: Lessons from the EXTEND study on ximelagatran

Cited by 81 publications

References 10 publications

Prevention and Treatment of Venous Thromboembolism and Pulmonary Embolism: The Role of Novel Oral Anticoagulants

Prevention and Treatment of Venous Thromboembolism and Pulmonary Embolism: The Role of Novel Oral Anticoagulants

Influence of Fondaparinux Versus Nadroparin Calcium Thromboprophylaxis on Clinical Parameters Following Total Knee Arthroplasty

Direct Thrombin Inhibitors

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