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Dabigatran Etexilate

A Review of its Use in the Prevention of Stroke and Systemic Embolism in Patients with Atrial Fibrillation

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Abstract

The need for safe, effective, and easily administered and monitored antithrombotic treatments that do not have the issues common to warfarin treatment has led to the development of new anticoagulant drugs. Dabigatran etexilate (Pradaxa®, Pradax™) is a prodrug of the direct thrombin inhibitor dabigatran, a direct, reversible, potent inhibitor of thrombin. Dabigatran does not interact with food, and is associated with very few known drug interactions.

Dabigatran etexilate, at dosages of 110 and 150 mg twice daily, was shown to be noninferior to warfarin with regard to the incidence of stroke or systemic embolism in a large, randomized, partially blinded, multicenter study in a wide spectrum of patients with atrial fibrillation. Moreover, the higher dosage was associated with significantly greater efficacy than warfarin in this regard. These results were supported by secondary endpoints and subgroup analyses.

In general, dabigatran etexilate is well tolerated, although it is associated with a higher rate of dyspepsia than warfarin. Major bleeding was as common in recipients of the higher dosage as, and less common in recipients of the lower dosage of dabigatran etexilate than, that in recipients of warfarin, and intracranial bleeding, life-threatening major bleeding, and total bleeding were less common in recipients of either dabigatran etexilate dosage than in warfarin recipients. However, the higher dosage of dabigatran etexilate was associated with a higher rate of gastrointestinal bleeding than warfarin. The incidence of hepatotoxicity did not significantly differ across treatment groups.

In conclusion, dabigatran etexilate 150 mg twice daily is more effective than warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation, and generally well tolerated, particularly with regard to bleeding endpoints compared with warfarin. It requires more frequent administration than warfarin, but provides multiple improvements to various issues associated with warfarin administration. Direct comparisons with other new anticoagulant drugs would be beneficial, as would further investigation into the effects in different patient populations, long-term effects, and the gastrointestinal bleeding and dyspepsia observed with dabigatran etexilate treatment. Dabigatran etexilate is a promising new option for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

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Correspondence to Karly P. Garnock-Jones.

Additional information

Various sections of the manuscript reviewed by: F. Angeli, Clinical Research Unit — Preventive Cardiology, S.M. della Misericordia Hospital, Perugia, Italy; C. Boersma, Department of Pharmacoepidemiology and Pharmacoeconomics, University of Groningen, Groningen, the Netherlands; C.K. Dragoumanis, Intensive Care Unit, University Hospital of Alexandroupolis, Alexandroupolis, Greece; M. Gattellari, Centre for Research Management, Evidence and Surveillance, University of New South Wales, Liverpool, New South Wales, Australia; G.Y.H. Lip, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, England; M. Thomsen, Ion-Channel Group, Danish Arrhythmia Research Centre, University of Copenhagen, Copenhagen, Denmark; D.M. Witt, Department of Pharmacy, Kaiser Permanente Colorado, Aurora, Colorado, USA.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘dabigatran etexilate’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE, and AdisBase search terms were (‘dabigatran etexilate’ or ‘dabigatran’) and ((‘stroke’ or ‘systemic embolism’) and (‘atrial fibrillation’)). Searches were last updated 17 November 2010.

Selection: Studies in patients with atrial fibrillation who received dabigatran etexilate for the prevention of stroke and systemic embolism. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Dabigatran etexilate, atrial fibrillation, stroke, systemic embolism, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability, pharmacoeconomics.

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Garnock-Jones, K.P. Dabigatran Etexilate. Am J Cardiovasc Drugs 11, 57–72 (2011). https://doi.org/10.2165/11206400-000000000-00000

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