Direct factor Xa inhibitors versus low molecular weight heparins or vitamin K antagonists for prevention of venous thromboembolism in elective primary hip or knee replacement or hip fracture repair

The relationship between venous thromboembolism and cancer has been known for many years, and there is solid scientific evidence addressing the adequate treatment of this condition in oncology patients. However, established prescribing habits, individual patient challenges, and uncertainty concerning treatment justifies poor adherence to published guidelines. This paper reviews venous thromboembolism treatment while focusing on vitamin K antagonists, low-molecular-weight heparins, and novel oral anticoagulants, namely in terms of their efficacy and limitations.

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Direct inhibitors of coagulation proteins – the end of the heparin and low-molecular-weight heparin era for anticoagulant therapy?

Thrombosis and Haemostasis ◽

10.1160/th09-02-0134 ◽

2009 ◽

Vol 102 (11) ◽

pp. 892-899 ◽

Cited By ~ 33

Author(s):

Elisabeth Perzborn ◽

Stefan Heitmeier ◽

Georges von Degenfeld ◽

Elke Dittrich-Wengenroth ◽

Anja Buchmüller ◽

...

Keyword(s):

Molecular Weight ◽

Vitamin K Antagonists ◽

Factor Xa ◽

Coagulation Cascade ◽

Thrombin Inhibitor ◽

Low Molecular Weight ◽

Direct Factor ◽

New Anticoagulants ◽

Coagulation Proteins ◽

The Eu

SummaryHeparins, either unfractionated or low-molecular-weight (UFH and LMWHs), and vitamin K antagonists (VKAs) are currently the anticoagulants of choice for the prevention of post-operative venous thromboembolism (VTE) and for the treatment of acute venous and arterial thromboembolism. While VKAs are widely used in the US, LMWHs are the standard of care in the EU. Although efficacious, these agents are associated with a number of drawbacks, such as the risk of heparin-induced thrombocytopenia, the need for frequent coagulation monitoring in the case of UFH and VKAs, and the parenteral mode of administration in the case of heparins, which can lead to problems associated with patient compliance. There is a need for new anticoagulants that overcome these limitations. Direct, small-molecule inhibitors of coagulation proteins targeting a single enzyme in the coagulation cascade – particularly thrombin or Factor Xa – have been developed in recent years. Two agents, the direct thrombin inhibitor dabigatran and the direct Factor Xa inhibitor rivaroxaban, have recently been approved in the EU and several other countries for the prevention of VTE after total hip or knee replacement surgery. Here we will review data that suggest that the antithrombin-independent mechanism of action of these agents, particularly that of direct Factor Xa inhibitors, leads to increased efficacy with similar safety profiles compared with the antithrombin-dependent heparins. Although the end of the heparins era is not to be expected, the new anticoagulants presented in this review potentially represent the future of anticoagulation.

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Low-molecular-weight heparins for the prevention of recurrent venous thromboembolism in patients with cancer: A systematic literature review of efficacy and cost-effectiveness

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155217727140 ◽

2017 ◽

Vol 25 (1) ◽

pp. 68-75 ◽

Cited By ~ 1

Author(s):

George Dranitsaris ◽

Lesley G Shane ◽

Seth Woodruff

Keyword(s):

Molecular Weight ◽

Venous Thromboembolism ◽

Cost Effectiveness ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Control Group ◽

Low Molecular Weight ◽

Low Molecular Weight Heparins ◽

Patients With Cancer ◽

Recurrent Venous Thromboembolism

Background Patients with cancer have an elevated risk of venous thromboembolism. Importantly, patients with cancer, who have metastatic disease, renal insufficiency, or are receiving anticancer therapy, have an even higher risk of a recurrent event. Similarly, the risk of recurrent venous thromboembolism is higher than the risk of an initial event. To reduce the risk, extended duration of prophylaxis for up to six months with low-molecular-weight heparins such as dalteparin, enoxaparin, nadroparin, and tinzaparin is recommended by international guidelines. In this paper, the clinical and economic literature is reviewed to provide evidenced based recommendations based on clinical benefit and economic value. Methods A systematic review of major databases was conducted from January 1996 to October 2016 for randomized controlled trials evaluating the four distinct low-molecular-weight heparins against a vitamin K antagonists control group for the prevention of recurrent venous thromboembolism in patients with active cancer. This was then followed by the application of the National Institute of Health and Clinical Excellence guidance to assess the quality of all trials that met the inclusion criteria. Finally, the cost-effectiveness literature supporting the value proposition of each product was reviewed. Results Six randomized trials met the inclusion criteria. There were one, two, and three trials that compared dalteparin, tinzaparin, and enoxaparin to a vitamin K antagonists control group. However, there were no trials for nadroparin in the setting of secondary venous thromboembolism prevention. In addition, only the dalteparin and one of the tinzaparin trials were of high quality and adequately powered. Of the two studies, only the dalteparin trial reported a statistically significant benefit in terms of venous thromboembolism absolute risk reduction when compared to a vitamin K antagonists control group (HR = 0.48; p = 0.002). In addition, there was robust pharmacoeconomic data from Canada, the Netherlands, France, and Austria supporting the cost-effectiveness of dalteparin for this indication. There were no such studies for any of the other agents. Conclusions The totality of high-quality clinical and cost-effectiveness data supports the use of dalteparin over other low-molecular-weight heparins for preventing recurrent venous thromboembolism in patients with cancer.

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