Journal of Thrombosis and Thrombolysis

, Volume 26, Issue 3, pp 167–174 | Cite as

Antithrombotic therapy in atrial fibrillation: guidelines translated for the clinician

  • Renato D. Lopes
  • Jonathan P. Piccini
  • Elaine M. Hylek
  • Christopher B. Granger
  • John H. AlexanderEmail author


Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, accounting for approximately one-third of hospitalizations for cardiac rhythm disturbances. The highest incidence of AF is in patients 70–80 years old and other high-risk populations. Although the diagnosis of AF is usually straightforward, effective treatment strategies are less well implemented. This is particularly true for antithrombotic therapy, which is very effective at preventing thromboembolic complications of AF. Stroke is the most significant morbidity in AF patients. The yearly risk of stroke increases from 1.5% for AF patients aged 50–59 to 23% for those aged 80–89. Ischemic strokes secondary to AF carry twice the risk of death when compared with strokes from other causes. We provide a practical and useful review of the most recent American College of Cardiology/American Heart Association/European Society of Cardiology guidelines-based care and future directions of antithrombotic therapy for patients with AF.


Atrial fibrillation Antithrombotic therapy Guidelines 


  1. 1.
    Fuster V, Rydén LE, Cannom DS et al (2006) 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 on collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 114:e257–e354. doi: 10.1161/CIRCULATIONAHA.106.177292 PubMedCrossRefGoogle Scholar
  2. 2.
    Go AS, Hylek EM, Phillips KA et al (2001) Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. JAMA 285:2370–2375. doi: 10.1001/jama.285.18.2370 PubMedCrossRefGoogle Scholar
  3. 3.
    Furberg CD, Psaty BM, Manolio TA et al (1994) Prevalence of atrial fibrillation in elderly subjects (the cardiovascular health study). Am J Cardiol 74:236–241. doi: 10.1016/0002-9149(94)90363-8 PubMedCrossRefGoogle Scholar
  4. 4.
    Feinberg WM, Blackshear JL, Laupacis A et al (1995) Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med 155:469–473. doi: 10.1001/archinte.155.5.469 PubMedCrossRefGoogle Scholar
  5. 5.
    Miyasaka Y, Barnes ME, Gersh BJ et al (2006) Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 114:119–125. doi: 10.1161/CIRCULATIONAHA.105.595140 PubMedCrossRefGoogle Scholar
  6. 6.
    Benjamin EJ, Wolf PA, D’Agostino RB et al (1998) Impact of atrial fibrillation on the risk of death: the Framingham heart study. Circulation 98:946–952PubMedGoogle Scholar
  7. 7.
    Wolf PA, D’Agostino RB, Belanger AJ et al (1991) Probability of stroke: a risk profile from the Framingham study. Stroke 22:312–318PubMedGoogle Scholar
  8. 8.
    Lairikyengbam SK, Anderson MH, Davies AG (2003) Present treatment options for atrial fibrillation. Postgrad Med J 79:67–73. doi: 10.1136/pmj.79.928.67 PubMedCrossRefGoogle Scholar
  9. 9.
    Singer DE, Albers GW, Dalen JE et al (2008) Antithrombotic therapy in atrial fibrillation: American College of chest physicians evidence-based clinical practice guidelines (8th edn). Chest 133:546S–592S. doi: 10.1378/chest.08-0678 PubMedCrossRefGoogle Scholar
  10. 10.
    Gage BF, Waterman AD, Shannon W et al (2001) Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation. JAMA 285:2864–2870. doi: 10.1001/jama.285.22.2864 PubMedCrossRefGoogle Scholar
  11. 11.
    Inoue H, Nozawa T, Hirai T et al (2006) Accumulation of risk factors increases risk of thromboembolic events in patients with nonvalvular atrial fibrillation. Circ J 70:651–656. doi: 10.1253/circj.70.651 PubMedCrossRefGoogle Scholar
  12. 12.
    Hylek EM, Go AS, Chang Y et al (2003) Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 349:1019–1026. doi: 10.1056/NEJMoa022913 PubMedCrossRefGoogle Scholar
  13. 13.
    Garcia DA, Regan S, Henault LE et al (2008) Risk of thromboembolism with short-term interruption of warfarin therapy. Arch Intern Med 168:63–69. doi: 10.1001/archinternmed.2007.23 PubMedCrossRefGoogle Scholar
  14. 14.
    Lopes RD, Pieper KS, Horton JR et al (2008) Short- and long-term outcomes following atrial fibrillation in patients with acute coronary syndromes with or without ST-segment elevation. Heart 94:867–873. doi: 10.1136/hrt.2007.134486 PubMedCrossRefGoogle Scholar
  15. 15.
    Orford JL, Fasseas P, Melby S et al (2004) Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation. Am Heart J 147:463–467. doi: 10.1016/j.ahj.2003.06.004 PubMedCrossRefGoogle Scholar
  16. 16.
    Khurram Z, Chou E, Minutello R et al (2006) Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding. J Invasive Cardiol 18:162–164PubMedGoogle Scholar
  17. 17.
    Karjalainen PP, Porela P, Ylitalo A et al (2007) Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting. Eur Heart J 28:726–732. doi: 10.1093/eurheartj/ehl488 PubMedCrossRefGoogle Scholar
  18. 18.
    Grines CL, Bonow RO, Casey DE Jr et al (2007) Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of physicians. J Am Coll Cardiol 49:734–739. doi: 10.1016/j.jacc.2007.01.003 PubMedCrossRefGoogle Scholar
  19. 19.
    Becker RC, Meade TW, Berger PB et al (2008) The primary and secondary prevention of coronary artery disease: American College of chest physicians evidence-based clinical practice guidelines (8th edn). Chest 133:776S–814S. doi: 10.1378/chest.08-0685 PubMedCrossRefGoogle Scholar
  20. 20.
    Dentali F, Douketis JD, Lim W et al (2007) Combined aspirin-oral anticoagulant therapy compared with oral anticoagulation therapy alone among patients at risk for cardiovascular disease: a meta-analysis of randomized trials. Arch Intern Med 167:117–124. doi: 10.1001/archinte.167.2.117 PubMedCrossRefGoogle Scholar
  21. 21.
    Hylek EM, Singer DE (1994) Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 120:897–902PubMedGoogle Scholar
  22. 22.
    Hylek EM, Skates SJ, Sheehan MA et al (1996) An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med 335:540–546. doi: 10.1056/NEJM199608223350802 PubMedCrossRefGoogle Scholar
  23. 23.
    Jones M, McEwan P, Morgan CL et al (2005) Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvular atrial fibrillation: a record linkage study in a large British population. Heart 91:472–477. doi: 10.1136/hrt.2004.042465 PubMedCrossRefGoogle Scholar
  24. 24.
    Boos CJ, Lip GY (2006) Ximelagatran: an eulogy. Thromb Res 118:301–304. doi: 10.1016/j.thromres.2006.02.012 PubMedCrossRefGoogle Scholar
  25. 25.
    Eriksson BI, Dahl OE, Buller HR et al (2005) A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. J Thromb Haemost 3:103–111. doi: 10.1111/j.1538-7836.2004.01100.x PubMedCrossRefGoogle Scholar
  26. 26.
    Stangier J, Rathgen K, Stähle H et al (2007) The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol 64:292–303. doi: 10.1111/j.1365-2125.2007.02899.x PubMedCrossRefGoogle Scholar
  27. 27.
    Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) With Dabigatran Etexilate NCT00262600. Accessed 01 July 2008
  28. 28.
    Bauer KA (2006) New anticoagulants: anti IIa vs anti Xa–is one better? J Thromb Thrombolysis 21:67–72. doi: 10.1007/s11239-006-5579-4 PubMedCrossRefGoogle Scholar
  29. 29.
    Bousser MG, Bouthier J, Buller HR et al (2008) Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet 371:315–321. doi: 10.1016/S0140-6736(08)60168-3 PubMedCrossRefGoogle Scholar
  30. 30.
    Evaluation of Weekly Subcutaneous Biotinylated Idraparinux Versus Oral Adjusted-Dose Warfarin to Prevent Stroke and Systemic Thromboembolic Events in Patients with Atrial Fibrillation (BOREALIS-AF) NCT00580216. Accessed 01 July 2008
  31. 31.
    Turpie AG (2007) Direct factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases. Arterioscler Thromb Vasc Biol 27:1238–1247. doi: 10.1161/ATVBAHA.107.139402 PubMedCrossRefGoogle Scholar
  32. 32.
    Kubitza D, Haas S (2006) Novel factor Xa inhibitors for prevention and treatment of thromboembolic diseases. Expert Opin Investig Drugs 15:843–855. doi: 10.1517/13543784.15.8.843 PubMedCrossRefGoogle Scholar
  33. 33.
    Lassen MR, Davidson BL, Gallus A et al (2007) The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement. J Thromb Haemost 5:2368–2375. doi: 10.1111/j.1538-7836.2007.02764.x PubMedCrossRefGoogle Scholar
  34. 34.
    Apixaban for the Prevention of Stroke in Subjects with Atrial Fibrillation (ARISTOTLE) NCT00412984. Accessed 01 July 2008
  35. 35.
    Phase A III Study of Apixaban in Patients with Atrial Fibrillation (AVERROES). NCT00496769. Accessed 01 July 2008
  36. 36.
    Piccini JP, Patel MR, Mahaffey KW et al (2008) Rivaroxaban, an oral direct factor Xa inhibitor. Expert Opin Investig Drugs 17:925–937. doi: 10.1517/13543784.17.6.925 PubMedCrossRefGoogle Scholar
  37. 37.
    A Study Comparing Once Daily Oral Rivaroxaban with Adjusted-Dose Oral Warfarin for the Prevention of Stroke in Subjects with Non-Valvular Atrial Fibrillation (ROCKET-AF) NCT00403767. Accessed on 01 July 2008

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Renato D. Lopes
    • 1
  • Jonathan P. Piccini
    • 1
  • Elaine M. Hylek
    • 2
  • Christopher B. Granger
    • 1
  • John H. Alexander
    • 1
    Email author
  1. 1.Duke Clinical Research InstituteDuke University Medical CenterDurhamUSA
  2. 2.Department of MedicineBoston University Medical CenterBostonUSA

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