Semin Thromb Hemost 2013; 39(02): 147-152
DOI: 10.1055/s-0033-1334812
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Anticoagulation Therapy for Atrial Fibrillation

Elaine M. Hylek
1   Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
› Author Affiliations
Further Information

Publication History

Publication Date:
08 February 2013 (online)

Abstract

Atrial fibrillation (AF) is the most common significant cardiac rhythm disorder, and its prevalence is increasing worldwide. Atrial fibrillation confers a fivefold increased risk of stroke, and these strokes are associated with significant mortality and disability. The vitamin K antagonist, warfarin, has been the mainstay of anticoagulant therapy for patients with AF, reducing the risk of stroke by 65%. Despite its efficacy, warfarin remains underused in clinical practice because of its variable dose response, diet and medication interactions, and need for frequent monitoring. Stroke prevention in AF has entered an exciting therapeutic era with new classes of targeted anticoagulants that avoid the many pitfalls of the vitamin K antagonists. Dabigatran, an oral thrombin inhibitor, and the factor Xa inhibitors, rivaroxaban and apixaban, have demonstrated efficacy for stroke prevention and a reduced risk of intracranial hemorrhage relative to warfarin. Translating the efficacy of clinical trials into effective use of these novel agents in clinical practice will require an understanding of their pharmacokinetic profiles, dose selection, and management in select clinical situations.

 
  • References

  • 1 Miyasaka Y, Barnes ME, Gersh BJ , 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 (2) 119-125
  • 2 Lloyd-Jones DM, Wang TJ, Leip EP , et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 2004; 110 (9) 1042-1046
  • 3 Heeringa J, van der Kuip DA, Hofman A , et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J 2006; 27 (8) 949-953
  • 4 Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22 (8) 983-988
  • 5 Jørgensen HS, Nakayama H, Reith J, Raaschou HO, Olsen TS. Acute stroke with atrial fibrillation. The Copenhagen Stroke Study. Stroke 1996; 27 (10) 1765-1769
  • 6 Sandercock P, Bamford J, Dennis M , et al. Atrial fibrillation and stroke: prevalence in different types of stroke and influence on early and long term prognosis (Oxfordshire community stroke project). BMJ 1992; 305 (6867) 1460-1465
  • 7 Lin HJ, Wolf PA, Kelly-Hayes M , et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996; 27 (10) 1760-1764
  • 8 Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146 (12) 857-867
  • 9 White HD, Gruber M, Feyzi J , et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med 2007; 167 (3) 239-245
  • 10 Gallagher AM, Setakis E, Plumb JM, Clemens A, van Staa TP. Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients. Thromb Haemost 2011; 106 (5) 968-977
  • 11 Wan Y, Heneghan C, Perera R , et al. Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review. Circ Cardiovasc Qual Outcomes 2008; 1 (2) 84-91
  • 12 Hylek EM, Go AS, Chang Y , et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003; 349 (11) 1019-1026
  • 13 O'Donnell M, Oczkowski W, Fang J , et al; Investigators of the Registry of the Canadian Stroke Network. Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: an observational study. Lancet Neurol 2006; 5 (9) 749-754
  • 14 Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 2011; 365 (21) 2002-2012
  • 15 Waldo AL, Becker RC, Tapson VF, Colgan KJ. NABOR Steering Committee. Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation. J Am Coll Cardiol 2005; 46 (9) 1729-1736
  • 16 Friberg L, Hammar N, Ringh M, Pettersson H, Rosenqvist M. Stroke prophylaxis in atrial fibrillation: who gets it and who does not? Report from the Stockholm Cohort-study on Atrial Fibrillation (SCAF-study). Eur Heart J 2006; 27 (16) 1954-1964
  • 17 Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GY. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 2010; 123 (7) 638-645 , e4
  • 18 Olsson SB. Executive Steering Committee of the SPORTIF III Investigators. 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 (9397) 1691-1698
  • 19 Albers GW, Diener HC, Frison L , et al; SPORTIF Executive Steering Committee for the SPORTIF V Investigators. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 2005; 293 (6) 690-698
  • 20 Connolly SJ, Ezekowitz MD, Yusuf S , et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
  • 21 Patel MR, Mahaffey KW, Garg J , et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
  • 22 Granger CB, Alexander JH, McMurray JJV , et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
  • 23 Ruff CT, Giugliano RP, Antman EM , et al. Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation-Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF-TIMI 48). Am Heart J 2010; 160 (4) 635-641
  • 24 Skanes AC, Healey JS, Cairns JA , et al; Canadian Cardiovascular Society Atrial Fibrillation Guidelines Committee. Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Can J Cardiol 2012; 28 (2) 125-136
  • 25 Camm AJ, Lip GY, De Caterina R , et al; ESC Committee for Practice Guidelines (CPG); Document Reviewers. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33 (21) 2719-2747
  • 26 You JJ, Singer DE, Howard PA , et al. Antithrombotic therapy for atrial fibrillation: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2 Suppl): e531S-e575S
  • 27 Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285 (22) 2864-2870
  • 28 Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; 137 (2) 263-272
  • 29 Fuster V, Rydén LE, Cannom DS , et al; American College of Cardiology Foundation/American Heart Association Task Force. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2011; 123 (10) e269-e367
  • 30 Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120 (11) 897-902
  • 31 Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16 (1) 31-41
  • 32 Walenga JM, Adiguzel C. Drug and dietary interactions of the new and emerging oral anticoagulants. Int J Clin Pract 2010; 64 (7) 956-967
  • 33 Lin JH, Yamazaki M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet 2003; 42 (1) 59-98
  • 34 Ageno W, Gallus A, Wittkowsky A , et al. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis. ACCP evidence-based guidelines (Ninth Edition). Chest 2012; 141 (2 Suppl): e44S-e88S
  • 35 Avorn J. The relative cost-effectiveness of anticoagulants: obvious, except for the cost and the effectiveness. Circulation 2011; 123 (22) 2519-2521
  • 36 Cutler DM, Everett W. Thinking outside the pillbox—medication adherence as a priority for health care reform. N Engl J Med 2010; 362 (17) 1553-1555
  • 37 Reinecke H, Brand E, Mesters R , et al. Dilemmas in the management of atrial fibrillation in chronic kidney disease. J Am Soc Nephrol 2009; 20 (4) 705-711
  • 38 Fox KAA, Piccini JP, Wojdyla D , et al. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur Heart J 2011; 32 (19) 2387-2394
  • 39 Eikelboom JW, Wallentin L, Connolly SJ , 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 (21) 2363-2372
  • 40 Hohnloser SH, Hijazi Z, Thomas L , et al. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J 2012; 33 (22) 2821-2830
  • 41 Kaatz S, Kouides PA, Garcia DA , et al. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol 2012; 87 (Suppl. 01) S141-S145
  • 42 Hankey GJ, Eikelboom JW. Dabigatran etexilate: a new oral thrombin inhibitor. Circulation 2011; 123 (13) 1436-1450
  • 43 Wallentin L, Yusuf S, Ezekowitz MD , et al; RE-LY investigators. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 2010; 376 (9745) 975-983
  • 44 Van Spall HG, Wallentin L, Yusuf S , et al. Variation in warfarin dose adjustment practice is responsible for differences in the quality of anticoagulation control between centers and countries: an analysis of patients receiving warfarin in the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial. Circulation 2012; 126 (19) 2309-2316