Chest
Volume 141, Issue 2, Supplement, February 2012, Pages e44S-e88S
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Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physician Evidence-Based Clinical Practice Guidelines Online Only Articles
Oral Anticoagulant Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

https://doi.org/10.1378/chest.11-2292Get rights and content

Background

The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management.

Methods

We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban.

Results

The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal.

Conclusions

There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban.

Section snippets

Pharmacology

VKAs produce their anticoagulant effect by interfering with the cyclic interconversion of vitamin K and its 2,3 epoxide (vitamin K epoxide), thereby modulating the γ-carboxylation of glutamate residues (Gla) on the N-terminal regions of vitamin K-dependent proteins (Fig 1).1, 2, 3, 4, 5, 6, 7, 8 The vitamin K-dependent coagulation factors II, VII, IX, and X require γ-carboxylation for their procoagulant activity, and treatment with VKAs results in the hepatic production of partially

Direct Thrombin Inhibitors: Dabigatran Etexilate

Dabigatran is a selective, reversible, direct thrombin inhibitor given as dabigatran etexilate, an orally absorbable prodrug, since dabigatran itself is a strongly polar molecule that is not absorbed from the gut. Phase 3 clinical studies reported to date have evaluated the use of dabigatran etexilate for the prevention of VTE after elective total knee or hip arthroplasty, for therapy of VTE, and to prevent stroke or systemic embolism in nonvalvular AF. The drug is approved in many countries

Direct Factor Xa Inhibitors: Rivaroxaban

Rivaroxaban is a direct factor Xa inhibitor and is currently approved in many countries, including the United States, for the prevention of VTE in patients undergoing total hip or knee replacement surgery. The drug is undergoing an extensive clinical development program in other clinical settings, including the treatment of VTE and the prevention of acute ischemic stroke in patients with AF. In phase III clinical trials, rivaroxaban was found to be more effective than the low-molecular-weight

Conclusion

Over the last decades, a large amount of research has been addressed to improve the understanding of the mechanisms of warfarin, acenocoumarol, and phenprocoumon and to improve the management of patients treated with these VKAs. Several studies have in particular identified some genetic factors associated with the individual responses to VKAs and several drugs, foods, and environmental factors that can interact with these compounds. Several induction and maintenance strategies have been

Acknowledgments

Author contributions: As Topic Editor, Dr Ageno oversaw the development of this article, including any analysis and subsequent development of the information contained herein

Dr Ageno: contributed as Topic Editor.

Dr Gallus: contributed as a panelist.

Dr Wittkowsky: contributed as a panelist.

Dr Crowther: contributed as a panelist.

Dr Hylek: contributed as a panelist.

Dr Palareti: contributed as a panelist.

Financial/nonfinancial disclosures: In summary, the authors have reported to CHEST the

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    Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758] and Bayer Schering Pharma AG. Support in the form of educational grants was also provided by Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; and sanofi-aventis US.

    Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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