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Dabigatran: Uncharted Waters and Potential Harms

2012; American College of Physicians; Volume: 157; Issue: 1 Linguagem: Inglês

10.7326/0003-4819-157-1-201207030-00467

1539-3704

Ryan P. Radecki,

Pharmacovigilance and Adverse Drug Reactions

Ideas and Opinions3 July 2012Dabigatran: Uncharted Waters and Potential HarmsRyan P. Radecki, MDRyan P. Radecki, MDFrom the University of Texas Health Science Center at Houston, Houston, Texas.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-1-201207030-00467 SectionsSupplemental MaterialAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This article has been corrected. The original version (PDF) is appended to this article as a supplement.This past November, an eye-opening headline was printed in the German newspaper Der Speigel (1): "Boehringer bestätigt Todesfälle durch Schlaganfal-Mittel" ("Boehringer Confirms Deaths Due to Stroke Drug"). Mainstream awareness of complications associated with dabigatran, the oral direct thrombin inhibitor from Boehringer Ingelheim, comes in tandem with alarms raised in the medical community about serious adverse events. After an Institute for Safe Medication Practices publication about an influx of reports of dabigatran-related adverse events (2), the U.S. Food and Drug Administration recently noted the ...References1. Boehringer bestätigt Todesfälle durch Schlaganfal-Mittel. Der Spiegel; 2011. Accessed at www.spiegel.de/wissenschaft/medizin/gerinnungshemmer-boehringer-bestaetigt-todesfaelle-durch-schlaganfall-mittel-a-795546.html on 16 May 2012. Google Scholar2. Moore TJ, Cohen MR, Furberg CD. Signals for Two Newly Approved Drugs and 2010 Annual Summary. QuarterWatch 2010 Quarter 4. Alexandria, VA: Institute for Safe Medication Practices; 2011. Google Scholar3. U.S. Food and Drug Administration. FDA Drug Safety Communication: Safety review of post-market reports of serious bleeding events with the anticoagulant Pradaxa (dabigatran etexilate mesylate). Silver Spring, MD: U.S. Food and Drug Administration; 7 December 2011. Google Scholar4. 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Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011;123:2363-72. [PMID: 21576658] CrossrefMedlineGoogle Scholar9. Liesenfeld KH, Lehr T, Dansirikul C, Reilly PA, Connolly SJ, Ezekowitz MD, et al. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial. J Thromb Haemost. 2011;9:2168-75. [PMID: 21972820] CrossrefMedlineGoogle Scholar10. Legrand M, Mateo J, Aribaud A, Ginisty S, Eftekhari P, Huy PT, et al. The use of dabigatran in elderly patients. Arch Intern Med. 2011;171:1285-6. [PMID: 21788545] CrossrefMedlineGoogle Scholar11. Casado Naranjo I, Portilla-Cuenca JC, Jiménez Caballero PE, Calle Escobar ML, Romero Sevilla RM. Fatal intracerebral hemorrhage associated with administration of recombinant tissue plasminogen activator in a stroke patient on treatment with dabigatran. Cerebrovasc Dis. 2011;32:614-5. [PMID: 22133608] CrossrefMedlineGoogle Scholar12. van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, et al. Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103:1116-27. [PMID: 20352166] CrossrefMedlineGoogle Scholar13. Cotton BA, McCarthy JJ, Holcomb JB. Acutely injured patients on dabigatran [Letter]. N Engl J Med. 2011;365:2039-40. [PMID: 22111735] CrossrefMedlineGoogle Scholar14. Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124:1573-9. [PMID: 21900088] CrossrefMedlineGoogle Scholar15. Zhou W, Schwarting S, Illanes S, Liesz A, Middelhoff M, Zorn M, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke. 2011;42:3594-9. [PMID: 21998060] CrossrefMedlineGoogle Scholar16. Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials. Arch Intern Med. 2012;172:397-402. [PMID: 22231617] CrossrefMedlineGoogle Scholar17. Freeman JV, Zhu RP, Owens DK, Garber AM, Hutton DW, Go AS, et al. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med. 2011;154:1-11. [PMID: 21041570] LinkGoogle Scholar18. Mega JL, Braunwald E, Wiviott SD, Bassand JP, Bhatt DL, Bode C, et al; ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366:9-19. [PMID: 22077192] CrossrefMedlineGoogle Scholar19. Alexander JH, Lopes RD, James S, Kilaru R, He Y, Mohan P, et al; APPRAISE-2 Investigators. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med. 2011;365:699-708. [PMID: 21780946] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From the University of Texas Health Science Center at Houston, Houston, Texas.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-2956.Corresponding Author: Ryan P. Radecki, MD, Department of Emergency Medicine, University of Texas Health Science Center at Houston, 6431 Fannin Street, JJL 450, Houston, TX 77030; e-mail, Ryan.P.[email protected]tmc.edu.Author Contributions: Conception and design: R.P. Radecki.Analysis and interpretation of the data: R.P. Radecki.Drafting of the article: R.P. Radecki.Critical revision of the article for important intellectual content: R.P. Radecki.Final approval of the article: R.P. Radecki.Collection and assembly of data: R.P. Radecki.This article was published at www.annals.org on 29 May 2012. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoCorrection: Dabigatran: Uncharted Waters and Potential HarmsAdverse Effects of Dabigatran Patricio A. Pazmiño Adverse Effects of Dabigatran Ryan P. 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Pazmiño, MD, PhDCorrection: Dabigatran: Uncharted Waters and Potential HarmsActualización en anticoagulantes II: nuevos anticoagulantes orales 3 July 2012Volume 157, Issue 1Page: 66-68KeywordsAdverse eventsAtrial fibrillationBlood plasmaHemorrhageSafetyStrokeThrombosisVenous thromboembolism ePublished: 3 July 2012 Issue Published: 3 July 2012 CopyrightCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...