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Review Article| Volume 34, ISSUE 3, P443-452, September 2014

Pharmacology and Safety of New Oral Anticoagulants

The Challenge of Bleeding Persists

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      References

        • Kannel W.B.
        • Benjamin E.J.
        Status of the epidemiology of atrial fibrillation.
        Med Clin North Am. 2008; 92 (ix): 17-40
        • Deitelzweig S.B.
        • Johnson B.H.
        • Lin J.
        • et al.
        Prevalence of clinical venous thromboembolism in the USA: current trends and future projections.
        Am J Hematol. 2011; 86: 217-220
        • Levy J.H.
        • Faraoni D.
        • Spring J.L.
        • et al.
        Managing new oral anticoagulants in the perioperative and intensive care unit setting.
        Anesthesiology. 2013; 118: 1466-1474
      1. Dabigatran prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield (CT)2013
      2. Dabigatran product monograph. Boehringer Ingelheim Canada Ltd, Burlington (Canada)2012
      3. Dabigatran summary of product characteristics. Boehringer Ingelheim Limited, Bracknell (United Kingdom)2012
      4. Dabigatran prescribing information. Boehringer Ingelheim Pty Limited, North Ryde (Australia)2013
      5. Boehringer Ingelheim pharmaceuticals I. PRAZAXA® (dabigatran etexilate) approved in Japan for stroke prevention in atrial fibrillation 2011. Available at: https://www.boehringer-ingelheim.com/news/news_releases/press_releases/2011/21_january_2011_dabigatranetexilate.html. Accessed July 4, 2014.

      6. Apixaban summary of product characteristics. Bristol-Myers Squibb/Pfizer EEIG, Uxbridge (United Kingdom)2011
      7. Apixaban prescribing information. Bristol-Myers Squibb Company, Princeton (NJ)2012
      8. Apixaban product monograph. Pfizer Canada Inc, Kirkland (Canada)2012
      9. Rivaroxaban prescribing information. Janssen Pharmaceuticals, Inc, Titusville (NJ)2013
      10. Rivaroxaban product monograph. Bayer Inc, Toronto (Canada)2013
      11. Rivaroxaban summary of product characteristics. Bayer Pharma AG, Berlin (Germany)2013
      12. Edoxaban package insert. Daiichi Sankyo Company Ltd, Tokyo (Japan)2011
      13. Available at: http://www.clinicaltrials.gov. Accessed September 30, 2013.

        • Baker W.L.
        • Phung O.J.
        Systematic review and adjusted indirect comparison meta-analysis of oral anticoagulants in atrial fibrillation.
        Circ Cardiovasc Qual Outcomes. 2012; 5: 711-719
        • Dentali F.
        • Riva N.
        • Crowther M.
        • et al.
        Efficacy and safety of the novel oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of the literature.
        Circulation. 2012; 126: 2381-2391
        • Connolly S.J.
        • Ezekowitz M.D.
        • Yusuf S.
        • et al.
        Dabigatran versus warfarin in patients with atrial fibrillation.
        N Engl J Med. 2009; 361: 1139-1151
        • Granger C.B.
        • Alexander J.H.
        • McMurray J.J.
        • et al.
        Apixaban versus warfarin in patients with atrial fibrillation.
        N Engl J Med. 2011; 365: 981-992
        • Lopes R.D.
        • Al-Khatib S.M.
        • Wallentin L.
        • et al.
        Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation: a secondary analysis of a randomised controlled trial.
        Lancet. 2012; 380: 1749-1758
        • Patel M.R.
        • Mahaffey K.W.
        • Garg J.
        • et al.
        Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.
        N Engl J Med. 2011; 365: 883-891
        • Lassen M.R.
        • Gallus A.
        • Raskob G.E.
        • et al.
        Apixaban versus enoxaparin for thromboprophylaxis after hip replacement.
        N Engl J Med. 2010; 363: 2487-2498
        • Schulman S.
        • Kearon C.
        Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.
        J Thromb Haemost. 2005; 3: 692-694
      14. US Food and Drug Administration approves Kcentra for the urgent reversal of anticoagulation in adults with major bleeding. 2013 Available at: http://www.fda.gov/NewsEvents/Newsroom/Pressannouncements/ucm350026.htm. Accessed November 5, 2013.

      15. US Food and Drug Administration. Coumadin official FDA information, side effects and uses. 2011. Available at: http://www.drugs.com/pro/coumadin.html. Accessed September 30, 2013.

        • Fareed J.
        • Hoppensteadt D.
        • Walenga J.
        • et al.
        Pharmacodynamic and pharmacokinetic properties of enoxaparin: implications for clinical practice.
        Clin Pharm. 2003; 42: 1043-1057
      16. sanofi-aventis. Enoxaparin—Highlights of prescribing information. 2008. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020164s083lbl.pdf. Accessed November 5, 2013.

        • Eikelboom J.W.
        • Weitz J.I.
        New anticoagulants.
        Circulation. 2010; 121: 1523-1532
        • van Veen J.J.
        • Maclean R.M.
        • Hampton K.K.
        • et al.
        Protamine reversal of low molecular weight heparin: clinically effective?.
        Blood Coagul Fibrinolysis. 2011; 22: 565-570
        • Holster I.L.
        • Valkhoff V.E.
        • Kuipers E.J.
        • et al.
        New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis.
        Gastroenterology. 2013; 145 (e15): 105-112
        • Mitchell S.A.
        • Simon T.A.
        • Raza S.
        • et al.
        The efficacy and safety of oral anticoagulants in warfarin-suitable patients with nonvalvular atrial fibrillation: systematic review and meta-analysis.
        Clin Appl Thromb Hemost. 2013; 19: 619-631
        • Harper P.
        • Young L.
        • Merriman E.
        Bleeding risk with dabigatran in the frail elderly.
        N Engl J Med. 2012; 366: 864-866
        • Adam S.S.
        • McDuffie J.R.
        • Ortel T.L.
        • et al.
        Comparative effectiveness of warfarin and new oral anticoagulants for the management of atrial fibrillation and venous thromboembolism: a systematic review.
        Ann Intern Med. 2012; 157: 796-807
        • Southworth M.R.
        • Reichman M.E.
        • Unger E.F.
        Dabigatran and postmarketing reports of bleeding.
        N Engl J Med. 2013; 368: 1272-1274
      17. US Food and Drug Administration. Pradaxa (dabigatran etexilate mesylate): drug safety communication—safety review of post-market reports of serious bleeding events. 2012. Available at: http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm282820.htm. Accessed August 30, 2013.

        • Büller H.R.
        • Prins M.H.
        • Lensin A.W.
        • et al.
        Oral rivaroxaban for the treatment of symptomatic pulmonary embolism.
        N Engl J Med. 2012; 366: 1287-1297
        • Lassen M.R.
        • Raskob G.E.
        • Gallus A.
        • et al.
        Apixaban or enoxaparin for thromboprophylaxis after knee replacement.
        N Engl J Med. 2009; 361: 594-604
        • Schulman S.
        • Kearon C.
        • Kakkar A.K.
        • et al.
        Dabigatran versus warfarin in the treatment of acute venous thromboembolism.
        N Engl J Med. 2009; 361: 2342-2352
        • Lassen M.R.
        • Raskob G.E.
        • Gallus A.
        • et al.
        Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial.
        Lancet. 2010; 375: 807-815
        • Bauersachs R.
        • Berkowitz S.D.
        • Brenner B.
        • et al.
        Oral rivaroxaban for symptomatic venous thromboembolism.
        N Engl J Med. 2010; 363: 2499-2510
        • Dogliotti A.
        • Paolasso E.
        • Giugliano R.P.
        Novel oral anticoagulants in atrial fibrillation: a meta-analysis of large, randomized, controlled trials vs warfarin.
        Clin Cardiol. 2013; 36: 61-67
        • Biondi-Zoccai G.
        • Malavasi V.
        • D'Ascenzo F.
        • et al.
        Comparative effectiveness of novel oral anticoagulants for atrial fibrillation: evidence from pair-wise and warfarin-controlled network meta-analyses.
        HSR Proc Intensive Care Cardiovasc Anesth. 2013; 5: 40-54
        • Ntaios G.
        • Papavasileiou V.
        • Diener H.C.
        • et al.
        Nonvitamin-K-antagonist oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack: a systematic review and meta-analysis of randomized controlled trials.
        Stroke. 2012; 43: 3298-3304
        • Majeed A.
        • Hwang H.G.
        • Connolly S.J.
        • et al.
        Management and outcomes of major bleeding during treatment with dabigatran or warfarin.
        Circulation. 2013; 128: 2325-2332
        • Neumann I.
        • Rada G.
        • Claro J.C.
        • et al.
        Oral direct factor Xa inhibitors versus low-molecular-weight heparin to prevent venous thromboembolism in patients undergoing total hip or knee replacement: a systematic review and meta-analysis.
        Ann Intern Med. 2012; 156: 710-719
        • Adam S.S.
        • McDuffie J.R.
        • Lachiewicz P.F.
        • et al.
        Comparative effectiveness of new oral anticoagulants and standard thromboprophylaxis in patients having total hip or knee replacement: a systematic review.
        Ann Intern Med. 2013; 159: 275-284
      18. Sobieraj DM, Coleman CI, Tongbram V, et al, editors. Venous thromboembolism prophylaxis in orthopedic surgery. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012. Mar. Report No.: 12-EHC020-EF.

        • Garcia D.A.
        • Baglin T.P.
        • Weitz J.I.
        • et al.
        Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines.
        Chest. 2012; 141: e24S-e43S
        • Levi M.M.
        • Eerenberg E.
        • Lowenberg E.
        • et al.
        Bleeding in patients using new anticoagulants or antiplatelet agents: risk factors and management.
        Neth J Med. 2010; 68: 68-76
        • Pengo V.
        • Crippa L.
        • Falanga A.
        • et al.
        Questions and answers on the use of dabigatran and perspectives on the use of other new oral anticoagulants in patients with atrial fibrillation. A consensus document of the Italian Federation of Thrombosis Centers (FCSA).
        Thromb Haemost. 2011; 106: 868-876
        • Turpie A.G.
        • Kreutz R.
        • Llau J.
        • et al.
        Management consensus guidance for the use of rivaroxaban—an oral, direct factor Xa inhibitor.
        Thromb Haemost. 2012; 108: 876-886
        • Heidbuchel H.
        • Verhamme P.
        • Alings M.
        • et al.
        EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary.
        Eur Heart J. 2013; 34: 2094-2106
        • Lazo-Langner A.
        • Lang E.S.
        • Douketis J.
        Clinical review: clinical management of new oral anticoagulants: a structured review with emphasis on the reversal of bleeding complications.
        Crit Care. 2013; 17: 230
        • Ortel T.L.
        Perioperative management of patients on chronic antithrombotic therapy.
        Blood. 2012; 120: 4699-4705
      19. US Food and Drug Administration. Safety announcement—Updated recommendations to decrease risk of spinal column bleeding and paralysis in patients on low molecular weight heparins. 2013. Available at: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM373735.pdf. Accessed November 5, 2013.

        • Huisman M.V.
        • Lip G.Y.
        • Diener H.C.
        • et al.
        Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: resolving uncertainties in routine practice.
        Thromb Haemost. 2012; 107: 838-847
        • Young E.
        • Cosmi B.
        • Weitz J.
        • et al.
        Comparison of the non-specific binding of unfractionated heparin and low molecular weight heparin (Enoxaparin) to plasma proteins.
        Thromb Haemost. 1993; 70: 625-630