Review ArticleClinical Review

Novel Anticoagulants in Atrial Fibrillation: A Primer for the Primary Physician

Martina Mookadam, Fadi E. Shamoun and Farouk Mookadam
The Journal of the American Board of Family Medicine July 2015, 28 (4) 510-522; DOI: https://doi.org/10.3122/jabfm.2015.04.140297

References

  1. 1.↵
    1. Fuster V,
    2. Rydén LE,
    3. Cannom DS,
    4. et al
    ; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; European Heart Rhythm Association; Heart Rhythm Society. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006;114:e257–354.
    OpenUrlFREE Full Text
  2. 2.↵
    1. Camm AJ,
    2. Kirchhof P,
    3. Lip GY,
    4. et al
    . Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010;31:2369–429.
    OpenUrlFREE Full Text
  3. 3.↵
    1. Lip GY,
    2. Tse HF,
    3. Lane DA
    . Atrial fibrillation. Lancet 2012;379:648–61.
    OpenUrlCrossRefPubMedWeb of Science
  4. 4.↵
    1. Gladstone DJ,
    2. Bui E,
    3. Fang J,
    4. et al
    . Potentially preventable strokes in high-risk patients with atrial fibrillation who are not adequately anticoagulated. Stroke 2009;40:235–40.
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Miyasaka Y,
    2. Barnes ME,
    3. Gersh BJ,
    4. et al
    . Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006;114:119–25.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Aberg H
    . Atrial fibrillation. I. A study of atrial thrombosis and systemic embolism in a necropsy material. Acta Med Scand 1969;185:373–9.
    OpenUrlPubMedWeb of Science
  7. 7.↵
    1. Stoddard MF,
    2. Dawkins PR,
    3. Prince CR,
    4. Ammash NM
    . Left atrial appendage thrombus is not uncommon in patients with acute atrial fibrillation and a recent embolic event: a transesophageal echocardiographic study. J Am Coll Cardiol 1995;25:452–9.
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Washington, DC: Heart Rhythm Society. Available from: http://www.hrsonline.org/Practice-Guidance/Clinical-Guidelines-Documents/Focused-Update-on-the-Management-of-Patients-With-Atrial-Fibrillation/2014-Guideline-for-the-Management-of-Patients-With-AFib#axzz3cCj7Luwn. Accessed May 15, 2015.
  9. 9.↵
    1. Lane DA,
    2. Lip GY
    . Use of the CHA(2)DS(2)-VASc and HAS-BLED scores to aid decision making for thromboprophylaxis in nonvalvular atrial fibrillation. Circulation 2012;126:860–5.
    OpenUrlFREE Full Text
  10. 10.↵
    1. Hart RG,
    2. Pearce LA,
    3. Asinger RW,
    4. Herzog CA
    . Warfarin in atrial fibrillation patients with moderate chronic kidney disease. Clin J Am Soc Nephrol 2011;6:2599–604.
    OpenUrlAbstract/FREE Full Text
  11. 11.
    1. Lip GY
    . Implications of the CHA(2)DS(2)-VASc and HAS-BLED Scores for thromboprophylaxis in atrial fibrillation. Am J Med 2011;124:111–4.
    OpenUrlCrossRefPubMedWeb of Science
  12. 12.↵
    1. Pisters R,
    2. Lane DA,
    3. Nieuwlaat R,
    4. de Vos CB,
    5. Crijns HJ,
    6. Lip GY
    . A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010;138:1093–100.
    OpenUrlCrossRefPubMedWeb of Science
  13. 13.↵
    1. Banerjee A,
    2. Lane DA,
    3. Torp-Pedersen C,
    4. Lip GY
    . Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real world’ atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost 2012;107:584–9.
    OpenUrlPubMed
  14. 14.↵
    1. Hirsh J,
    2. Dalen J,
    3. Anderson DR,
    4. et al
    . Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 2001;119:8S–21S.
    OpenUrlCrossRefPubMedWeb of Science
  15. 15.↵
    1. Heneghan C,
    2. Alonso-Coello P,
    3. Garcia-Alamino JM,
    4. Perera R,
    5. Meats E,
    6. Glasziou P
    . Self-monitoring of oral anticoagulation: a systematic review and meta-analysis. Lancet 2006;367:404–11.
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    1. Siddiqui FM,
    2. Qureshi AI
    . Dabigatran etexilate, a new oral direct thrombin inhibitor, for stroke prevention in patients with atrial fibrillation. Expert Opin Pharmacother 2010;11:1403–11.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Hohnloser SH
    . Stroke prevention versus bleeding risk in atrial fibrillation: a clinical dilemma. J Am Coll Cardiol 2011;57:181–3.
    OpenUrlCrossRefPubMedWeb of Science
  18. 18.↵
    1. Waldo AL,
    2. Becker RC,
    3. Tapson VF,
    4. Colgan KJ
    . Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation. J Am Coll Cardiol 2005;46:1729–36.
    OpenUrlCrossRefPubMedWeb of Science
  19. 19.↵
    1. Glader EL,
    2. Sjolander M,
    3. Eriksson M,
    4. Lundberg M
    . Persistent use of secondary preventive drugs declines rapidly during the first 2 years after stroke. Stroke 2010;41:397–401.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Ogilvie IM,
    2. Newton N,
    3. Welner SA,
    4. Cowell W,
    5. Lip GY
    . Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 2010;123:638–645.e4.
    OpenUrlCrossRefPubMedWeb of Science
  21. 21.↵
    1. Connolly SJ,
    2. Pogue J,
    3. Hart RG,
    4. et al
    . Effect of clopidogrel added to aspirin in patients with atrial fibrillation. New Engl J Med 2009;360:2066–78.
    OpenUrlCrossRefPubMedWeb of Science
  22. 22.↵
    1. Connolly S,
    2. Pogue J,
    3. Hart R,
    4. et al
    . Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006;367:1903–12.
    OpenUrlCrossRefPubMedWeb of Science
  23. 23.↵
    1. Mani H,
    2. Lindhoff-Last E
    . New oral anticoagulants in patients with nonvalvular atrial fibrillation: a review of pharmacokinetics, safety, efficacy, quality of life, and cost effectiveness. Drug Des Devel Ther 2014;8:789–98.
    OpenUrlPubMed
  24. 24.↵
    1. Albers GW,
    2. Diener HC,
    3. Frison L,
    4. et al
    . Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 2005;293:690–8.
    OpenUrlCrossRefPubMedWeb of Science
  25. 25.↵
    1. Olsson SB
    . Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet 2003;362:1691–8.
    OpenUrlCrossRefPubMedWeb of Science
  26. 26.↵
    1. Gorelick PB
    . Combining aspirin with oral anticoagulant therapy: is this a safe and effective practice in patients with atrial fibrillation? Stroke 2007;38:1652–4.
    OpenUrlFREE Full Text
  27. 27.↵
    1. Munar MY,
    2. Singh H
    . Drug dosing adjustments in patients with chronic kidney disease. Am Fam Physician 2007;75:1487–96.
    OpenUrlPubMedWeb of Science
  28. 28.↵
    1. Connolly SJ,
    2. Ezekowitz MD,
    3. Yusuf S,
    4. et al
    . Dabigatran versus warfarin in patients with atrial fibrillation. New Engl J Med 2009;361:1139–51.
    OpenUrlCrossRefPubMedWeb of Science
  29. 29.↵
    1. Eikelboom JW,
    2. Weitz JI
    . New anticoagulants. Circulation 2010;121:1523–32.
    OpenUrlFREE Full Text
  30. 30.↵
    1. Granger CB,
    2. Alexander JH,
    3. McMurray JJ,
    4. et al
    . Apixaban versus warfarin in patients with atrial fibrillation. New Engl J Med 2011;365:981–92.
    OpenUrlCrossRefPubMedWeb of Science
  31. 31.↵
    1. Patel MR,
    2. Mahaffey KW,
    3. Garg J,
    4. et al
    . Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. New Engl J Med 2011;365:883–91.
    OpenUrlCrossRefPubMedWeb of Science
  32. 32.↵
    1. Schirmer SH,
    2. Baumhakel M,
    3. Neuberger HR,
    4. et al
    . Novel anticoagulants for stroke prevention in atrial fibrillation: current clinical evidence and future developments. J Am Coll Cardiol 2010;56:2067–76.
    OpenUrlCrossRefPubMedWeb of Science
  33. 33.↵
    1. Southworth MR,
    2. Reichman ME,
    3. Unger EF
    . Dabigatran and postmarketing reports of bleeding. New Engl J Med 2013;368:1272–4.
    OpenUrlCrossRefPubMedWeb of Science
  34. 34.↵
    1. Weitz JI,
    2. Connolly SJ,
    3. Patel I,
    4. et al
    . Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation. Thromb Haemost 2010;104:633–41.
    OpenUrlCrossRefPubMedWeb of Science
  35. 35.↵
    1. Eikelboom JW,
    2. Wallentin L,
    3. Connolly SJ,
    4. 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.
    OpenUrlAbstract/FREE Full Text
  36. 36.↵
    1. Hijazi Z,
    2. Hohnloser SH,
    3. Oldgren J,
    4. et al
    . Efficacy and safety of dabigatran compared with warfarin in relation to baseline renal function in patients with atrial fibrillation: a RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) trial analysis. Circulation 2014;129:961–70.
    OpenUrlAbstract/FREE Full Text
  37. 37.↵
    1. Gage BF,
    2. Waterman AD,
    3. Shannon W,
    4. Boechler M,
    5. Rich MW,
    6. Radford MJ
    . Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001;285:2864–70.
    OpenUrlCrossRefPubMedWeb of Science
  38. 38.↵
    Product monograph. Pradaxa (dabigatran etexilate capsules). Burlington, ON: Boehringer Ingelheim Canada Ltd. Revised January 7, 2015. Available from: http://www.boehringer-ingelheim.ca/content/dam/internet/opu/ca_EN/documents/humanhealth/product_monograph/PradaxaPMEN.pdf. Accessed March 15, 2015.
  39. 39.↵
    Janssen Pharmaceuticals Inc. Xarelto (rivaroxaban). Revised January 2015. Available from: http://www.xareltohcp.com/sites/default/files/pdf/xarelto_0.pdf. Accessed March 15, 2015.
  40. 40.↵
    Product monograph. Eliquis (apixaban tablets). Montreal: Bristol-Myers Squibb Canada. February 20, 2015. Available from: http://www.pfizer.ca/en/our_products/products/monograph/313. Accessed May 15, 2015.
  41. 41.↵
    Daiichi Sankyo Inc. SAVAYSA (edoxaban). Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206316lbl.pdf. Accessed May 15, 2015.
  42. 42.↵
    1. Heidbuchel H,
    2. Verhamme P,
    3. Alings M,
    4. et al
    ; European Heart Rhythm Association. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625–51.
    OpenUrlAbstract/FREE Full Text
  43. 43.↵
    1. Ansell J
    . Warfarin versus new agents: interpreting the data. Hematology Am Soc Hematol Educ Program 2010;2010:221–8.
    OpenUrlAbstract/FREE Full Text
  44. 44.↵
    1. Go AS,
    2. Singer D,
    3. Cheetham C,
    4. et al
    . Mini-sentinel medical product assessment: a protocol for assessment of dabigatran. Version 2. Revised March 27, 2015. Available from: http://www.mini-sentinel.org/work_products/Assessments/Mini-Sentinel_Protocol-for-Assessment-of-Dabigatran.pdf. Accessed May 15, 2015.
  45. 45.↵
    1. Hernandez I,
    2. Baik SH,
    3. Pinera A,
    4. Zhang Y
    . Risk of bleeding with dabigatran in atrial fibrillation. JAMA Intern Med 2015;175:18–24.
    OpenUrlCrossRefPubMedWeb of Science
  46. 46.↵
    1. Baron TH,
    2. Kamath PS,
    3. McBane RD
    . Management of antithrombotic therapy in patients undergoing invasive procedures. New Engl J Med 2013;368:2113–24.
    OpenUrlCrossRefPubMedWeb of Science
  47. 47.↵
    1. Spyropoulos AC,
    2. Douketis JD
    . How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood 2012;120:2954–62.
    OpenUrlAbstract/FREE Full Text
  48. 48.↵
    1. Crowther M,
    2. Mathur V,
    3. Kitt MM,
    4. et al
    . A phase 2 randomized, double-blind, placebo-controlled trial demonstrating reversal of rivaroxaban-induced anticoagulation in healthy subjects by andexanet alfa (PRT064445), an antidote for Fxa inhibitors. Presented at the 55th American Society of Hematology Annual Meeting and Exposition, New Orleans, LA, December 7–10, 2013.
  49. 49.↵
    1. Lu G,
    2. DeGuzman FR,
    3. Hollenbach SJ,
    4. et al
    . A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med 2013;19:446–51.
    OpenUrlCrossRefPubMed
  50. 50.↵
    1. Lip GY,
    2. Agnelli G
    . Edoxaban: a focused review of its clinical pharmacology. Eur Heart J 2014;35:1844–55.
    OpenUrlAbstract/FREE Full Text
  51. 51.↵
    1. Knepper J,
    2. Horne D,
    3. Obi A,
    4. Wakefield TW
    . A systematic update on the state of novel anticoagulants and a primer on reversal and bridging. J Vasc Surg 2013;1:418–26.
    OpenUrl
  52. 52.↵
    Boehringer Ingelheim. Boehringer Ingelheim's Investigational Antidote for Pradaxa® (dabigatran etexilate mesylate) Receives FDA Breakthrough Therapy Designation. June 26, 2014. Available from: http://us.boehringer-ingelheim.com/news_events/press_releases/press_release_archive/2014/06-26-14-boehringer-ingelheim-investigational-antidote-pradaxa-dabigatran-etexilate-mesylate-fda-breakthrough-therapy-designation.html. Accessed May 15, 2015.
  53. 53.↵
    1. Fukuda T,
    2. Honda Y,
    3. Kamisato C,
    4. Morishima Y,
    5. Shibano T
    . Reversal of anticoagulant effects of edoxaban, an oral, direct factor Xa inhibitor, with haemostatic agents. Thromb Haemost 2012;107:253–9.
    OpenUrlPubMed
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