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Stroke Prevention in Atrial Fibrillation

Putting the Guidelines into Practice

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Abstract

Atrial fibrillation confers a 5-fold increase in risk of stroke. A number of drugs aimed at reducing this risk have been tested in randomized controlled trials. These include antiplatelet agents (singly and in combination); anticoagulants, including vitamin K antagonists and direct thrombin inhibitors; and anticoagulants with antiplatelet agents. Guidelines recommend that the choice of therapy should be determined by an assessment of underlying risk of stroke, with antiplatelet agents being indicated for people at low risk of stroke and anticoagulants for those at higher risk. The treatment decision is complicated by considerations of haemorrhage risk, with factors that increase risk of stroke also associated with increased risk of haemorrhage. Evidence from recent studies confirms that patients at high risk of stroke should be treated with anticoagulants, including elderly patients, provided that good international normalized ratio (INR) control can be maintained. Newer agents may enable a higher proportion of patients at high risk of stroke to be treated with anticoagulants than is currently the case. Decision making about people at moderate risk of stroke is less clear cut, and a choice of either an antiplatelet agent or an anticoagulant can be justified. For people at low risk of stroke, anticoagulation is not indicated.

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References

  1. National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006

    Google Scholar 

  2. Levy S, Camm AJ, Saksena S, et al. International consensus on nomenclature and classification of atrial fibrillation; a collaborative project of the Working Group on Arrhythmias and the Working Group on Cardiac Pacing of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Euro-pace 2003; 5(2): 119–22

    CAS  Google Scholar 

  3. Mant J, Wade DT, Winner S. Health care needs assessment: stroke. In: Stevens A, Raftery J, Mant J, et al., editors. Health care needs assessment: the epidemiologically based needs assessment reviews, first series. 2nd ed. Oxford: Radcliffe Medical Press, 2004: 141–244

    Google Scholar 

  4. Fitzmaurice DA, Hobbs FDR, Jowett S, et al. Screening versus routine practice in detection of atrial fibrillation in patients aged 65 or over: cluster randomised controlled trial. BMJ 2007; 335: 383

    Article  PubMed  Google Scholar 

  5. Levy S, Maarek M, Cournel P, et al. Characterisation of different subsets of atrial fibrillation in general practice in France: the ALFA Study. Circulation 1999; 99: 3028–35

    Article  PubMed  CAS  Google Scholar 

  6. Furberg CD, Psaty BM, Manolio TA, et al. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol 1994; 74: 236–41

    Article  PubMed  CAS  Google Scholar 

  7. Kannel WB, Wolf PA, Benjamin EJ, et al. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 1998; 82: 2–9N

    Article  Google Scholar 

  8. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham study. Stroke 1991; 22: 983–88

    Article  PubMed  CAS  Google Scholar 

  9. Rothwell PM, Coull AJ, Giles MF, et al. Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study). Lancet 2004; 363: 925–33

    Article  Google Scholar 

  10. Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007; 69: 546–54

    Article  Google Scholar 

  11. Stroke Risk in Atrial Fibrillation Working Group. Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation. Stroke 2008; 39: 1901–10

    Article  Google Scholar 

  12. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285: 2864–70

    Article  PubMed  CAS  Google Scholar 

  13. Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493–503

    Article  PubMed  CAS  Google Scholar 

  14. Aguilar MI, Hart R. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischaemic attacks. Cochrane Database Syst Rev 2005; (2): CD001927

    Google Scholar 

  15. Agilar MI, Hart R. Antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischaemic attacks. Cochrane Database Syst Rev 2005; (4): CD001925

    Google Scholar 

  16. Van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA 2002; 288: 2441–8

    Article  PubMed  Google Scholar 

  17. Mant JWF, Richards SH, Hobbs R, et al. Protocol for Birmingham Atrial Fibrillation Treatment of the Aged study (BAFTA): a randomised controlled trial of warfarin versus aspirin for stroke prevention in the management of atrial fibrillation in an elderly primary care population. BMC Cardiovasc Disord 2003; 3: 9

    Article  PubMed  Google Scholar 

  18. Rash A, Downes T, Portner R, et al. A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). Age Ageing 2007; 37: 151–6

    Article  Google Scholar 

  19. van Walraven C, Hart RG, Connolly S, et al. Effect of age on stroke prevention therapy in patients with atrial fibrillation: the Atrial Fibrillation Investigators. Stroke 2009; 40: 1410–6

    Article  PubMed  Google Scholar 

  20. The ACTIVE Writing Group on behalf of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anti-coagulation 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

    Article  Google Scholar 

  21. The Active Investigators. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009; 360: 2066–78

    Article  Google Scholar 

  22. ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet 2006; 367: 1665–73

    Article  Google Scholar 

  23. Stroke Prevention in Atrial Fibrillation Investigators. Adjusted dose warfarin versus low intensity, fixed dose warfarin plus aspirin for high risk patients with atrial fibrillation: stroke prevention in atrial fibrillation III randomised clinical trial. Lancet 1996; 348: 633–8

    Article  Google Scholar 

  24. Perez-Gomez F, Alegria E, Berjon J, et al. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. JACC 2004; 44: 1557–66

    PubMed  CAS  Google Scholar 

  25. Antithrombotic Trialists’ Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373: 1849–60

    Article  Google Scholar 

  26. Lip GY, Boos CJ. Antithrombotic treatment in atrial fibrillation. Heart 2006; 92: 155–61

    Article  PubMed  CAS  Google Scholar 

  27. Lip GYH. Don’t add aspirin for associated stable vascular disease in a patient with atrial fibrillation receiving anticoagulation. BMJ 2008; 336: 614–5

    Article  PubMed  Google Scholar 

  28. Dentali F, Douketis JD, Lim W, et al. Combined aspirin-oral anticoagulant therapy compared with oral anticoagulant therapy alone among patients at risk for cardiovascular disease: a meta-analysis of randomised trials. Arch Intern Med 2007; 167: 117–24

    Article  PubMed  CAS  Google Scholar 

  29. Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002; 347: 969–74

    Article  PubMed  CAS  Google Scholar 

  30. Flaker GC, Gruber M, Connolly SJ, et al. Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trial. Am Heart J 2006; 152: 967–73

    Article  PubMed  CAS  Google Scholar 

  31. Hart RG, Benavente O, Pearce LA. Increased risk of intracranial haemorrhage when aspirin is combined with warfarin: a meta-analysis and hypothesis. Cerebrovasc Dis 1999; 9: 215–7

    Article  PubMed  CAS  Google Scholar 

  32. The Medical Research Council’s General Practice Research Framework. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. Lancet 1998; 351: 233–41

    Article  Google Scholar 

  33. Connolly SJ, Eikelboom J, O’Donnell M, et al. Challenges of establishing new antithrombotic therapies in atrial fibrillation. Circulation 2007; 116: 449–55

    Article  PubMed  Google Scholar 

  34. 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: 1691–8

    Article  Google Scholar 

  35. 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: 690–8

    Article  Google Scholar 

  36. The AMADEUS Investigators. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet 2008; 371: 315–21

    Article  Google Scholar 

  37. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139–51

    Article  PubMed  CAS  Google Scholar 

  38. Hart RG, Pearce LA. Current status of stroke risk stratification in patients with atrial fibrillation. Stroke 2009; 40: 2607–10

    Article  PubMed  Google Scholar 

  39. National Collaborating Centre for Chronic Conditions. Atrial fibrillation: the management of atrial fibrillation. NICE Clinical Guideline 36. London: National Institute for Health and Clinical Excellence, 2006

    Google Scholar 

  40. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: executive summary. Circulation 2006; 114: 700–52

    Article  Google Scholar 

  41. Singer DE, Albers GW, Dalen JE, et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008; 133 (6 Suppl.): 546s–92s

    Google Scholar 

  42. Healey JS, Hart RG, Pogue J, et al. Risks and benefits of oral anticoagulation compared with clopidogrel plus aspirin in patients with atrial fibrillation according to stroke risk: the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE-W). Stroke 2008; 39: 1482–6

    Article  PubMed  CAS  Google Scholar 

  43. Lee BH, Park JS, Park JH, et al. The effect and safety of the antithrombotic therapies in patients with atrial fibrillation and CHADS2 score 1. J Cardiovasc Electrophysiol 2010; 21(5): 501–7

    Article  PubMed  Google Scholar 

  44. Gorin L, Faucheir L, Nonin E, et al. Antithrombotic treatment and the risk of death and stroke in patients with atrial fibrillation and a CHADS2 score=1. Thromb Haemost 2010; 103: 833–40

    Article  PubMed  CAS  Google Scholar 

  45. Singer DE, Chang Y, Fang MC. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009; 151: 297–305

    PubMed  Google Scholar 

  46. Sato H, Ishikawa K, Kitabatake A, et al. Low dose aspirin for prevention of stroke in low risk patients with atrial fibrillation. Japan Atrial Fibrillation Stroke Trial. Stroke 2006; 37: 447–51

    Article  PubMed  CAS  Google Scholar 

  47. Schulman S, Beyth RJ, Kearon C, et al. Haemorrhagic complications of anticoagulant and thrombolytic treatment. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008; 133 (6 Suppl.): 257s–98s

    Article  PubMed  CAS  Google Scholar 

  48. Hutten BA, Lensign AW, Kraaijenhagen RA, et al. Safety of treatment with oral anticoagulants in the elderly: a systematic review. Drugs Aging 1999; 14: 303–12

    Article  PubMed  CAS  Google Scholar 

  49. Laupacis A, Boysen G, Connolly S, et al. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994; 154: 1449–57

    Article  Google Scholar 

  50. Shireman TI, Howard PA, Kresowik TF, et al. Combined anticoagulant-antiplatelet use and major bleeding events in elderly atrial fibrillation patients. Stroke 2004; 35: 2362–7

    Article  PubMed  CAS  Google Scholar 

  51. Hylek EM, Evans-Molina C, Shea C, et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115: 2689–96

    Article  PubMed  CAS  Google Scholar 

  52. Palareti G, Hirsh H, Legnani C, et al. Bleeding complications of oral anticoagulant treatment: an inception-cohort prospective collaborative study (ISCOAT). Lancet 1996; 348: 423–8

    Article  PubMed  CAS  Google Scholar 

  53. Connolly SJ, Pogue J, Eikelboom J, et al. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centres and countries as measured by time in therapeutic range. Cicrulation 2008; 118: 2029–37

    Article  CAS  Google Scholar 

  54. Heneghan C, Alonso-Coello P, Garcia-Alamino JM, et al. Self-monitoring of oral anticoagulation: a systematic review and meta-analysis. Lancet 2006 Feb 4; 367(9508): 404–11

    Article  PubMed  CAS  Google Scholar 

  55. Poller L, Keown M, Ibrahim S, et al. An international multicenter randomized study of computer-assisted oral anticoagulant dosage vs. medical staff dosage. J Thromb Haemost 2008 Jun; 6(6): 935–43

    Article  PubMed  CAS  Google Scholar 

  56. Aquilante CL, Langaee TY, Lopez LM, et al. Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements. Clin Pharmacol Ther 2006; 79: 291–302

    Article  PubMed  CAS  Google Scholar 

  57. Klein TE, Altman RB, Eriksson N, et al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med 2009 Feb 19; 360(8): 753–64

    Article  PubMed  Google Scholar 

  58. Kangelaris KN, Bent S, Nussbaum RL, et al. Genetic testing before anticoagulation? A systematic review of pharmacogenetic dosing of warfarin. J Gen Intern Med 2009 May; 24(5): 656–64

    Article  PubMed  Google Scholar 

  59. Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly score (HAS-BLED) to assess one-year risk of major bleeding in atrial fibrillation patients: The Euro Heart Survey. Chest. Epub 2010 Mar 18

    Google Scholar 

  60. Gage BF, Yan Y, Milligan PE, et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006 Mar; 151(3): 713–9

    Article  PubMed  Google Scholar 

  61. Palareti G, Cosmi B. Bleeding with anticoagulation therapy — who is at risk, and how best to identify such patients. Thromb Haemost 2009 Aug; 102(2): 268–78

    PubMed  CAS  Google Scholar 

  62. 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: 1019–26

    Article  PubMed  CAS  Google Scholar 

  63. Serebruany VL, Steinbuhl SR, Berger PB, et al. Analysis of risk of bleeding complications after different doses of aspirin in 192036 patients enrolled in 31 randomised controlled trials. Am J Cardiol 2005; 95: 1218–22

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

No sources of funding were used to assist in the preparation of this article. Jonathan Mant has provided consultancy advice to Boehringer Ingelheim. Duncan Edwards has no conflicts of interest that are directly relevant to the content of this article.

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Mant, J., Edwards, D. Stroke Prevention in Atrial Fibrillation. Drugs Aging 27, 859–870 (2010). https://doi.org/10.2165/11538620-000000000-00000

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