Combined anticoagulation and antiplatelet therapy for high-risk patients with atrial fibrillation: A systematic review

Health Technology Assessment

Volumn 17, Issue 30, 2013, Pages 1-187

  Lane, D A ^a   Raichand, S ^a   Moore, D ^a   Connock, M ^a   Fry Smith, A ^a   Fitzmaurice, D A ^a  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACENOCOUMAROL; ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; ANTITHROMBOCYTIC AGENT; CLOPIDOGREL; DABIGATRAN; FLUINDIONE; IDRAPARINUX; PLACEBO; TRIFLUSAL; WARFARIN; XIMELAGATRAN;

ACUTE HEART INFARCTION; AGED; ARTICLE; BLEEDING; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; CAUSE OF DEATH; CEREBROVASCULAR ACCIDENT; COMBINATION CHEMOTHERAPY; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG EFFICACY; FEMALE; FOLLOW UP; HEART ATRIUM FIBRILLATION; HUMAN; MAJOR CLINICAL STUDY; MALE; MONOTHERAPY; MORTALITY; QUALITY OF LIFE; RISK ASSESSMENT; RISK BENEFIT ANALYSIS; RISK REDUCTION; SYSTEMATIC REVIEW; THROMBOEMBOLISM; TRANSIENT ISCHEMIC ATTACK; TREATMENT OUTCOME;

ANTICOAGULANTS; ASPIRIN; ATRIAL FIBRILLATION; DRUG THERAPY, COMBINATION; HEMORRHAGE; HUMANS; ISCHEMIC ATTACK, TRANSIENT; MYOCARDIAL INFARCTION; PLATELET AGGREGATION INHIBITORS; RISK; STROKE; THROMBOEMBOLISM;

EID: 84881036858     PISSN: 13665278     EISSN: 20464924     Source Type: Journal    
DOI: 10.3310/hta17300     Document Type: Article

References (97)

1. Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation-Executive summary: 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). Circulation 2006;114:700-52.
2. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, 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. http://dx.doi.org/10.1093/eurheartj/ehq278
3. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22:983-8. http://dx.doi.org/10.1161/01.STR.22.8.983
4. Wolf PA, Mitchell JB, Baker CS, Kannel WB, D'Agostino RB. Impact of atrial fibrillation on mortality, stroke, and medical costs. Arch Intern Med 1998;158:229-34. http://dx.doi.org/10.1001/ archinte.158.3.229
5. Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998;98:946-52. http://dx.doi. org/10.1161/01.CIR.98.10.946
6. Dorian P, Jung W, Newman D, Paquette M, Wood K, Ayers GM, et al. The impairment of healthrelated quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy. J Am Coll Cardiol 2000;36:1303-9. http://dx.doi.org/10.1016/ S0735-1097(00)00886-X
7. Thrall G, Lane D, Carroll D, Lip GYH. Quality of life in patients with atrial fibrillation: a systematic review. Am J Med 2006;119:448. http://dx.doi.org/10.1016/j.amjmed.2005.10.057
8. Heeringa J, van der Kuip DA, Hofman A, Kors JA, van HG, Stricker BH, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J 2006;27:949-53. http:// dx.doi.org/10.1093/eurheartj/ehi825
9. Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 2004;110:1042-6. http://dx.doi. org/10.1161/01.CIR.0000140263.20897.42
10. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, 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. http://dx.doi.org/10.1161/ CIRCULATIONAHA.105.595140
11. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, et al. 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 2001;285:2370-5. http://dx.doi.org/10.1001/jama.285.18.2370
12. Hobbs FD, Fitzmaurice DA, Mant J, Murray E, Jowett S, Bryan S, et al. A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study. Health Technol Assess 2005;9(40).
13. Jorgensen HS, Nakayama H, Reith J, Raaschou HO, Olsen TS. Acute stroke with atrial fibrillation. The Copenhagen Stroke Study. Stroke 1996;27:1765-9. http://dx.doi.org/10.1161/01.STR.27.10.1765
14. Steger C, Pratter A, Martinek-Bregel M, Avanzini M, Valentin A, Slany J, et al. Stroke patients with atrial fibrillation have a worse prognosis than patients without: data from the Austrian Stroke registry. Eur Heart J 2004;25:1734-40. http://dx.doi.org/10.1016/j.ehj.2004.06.030
15. Lin HJ, Wolf PA, Kelly-Hayes M, Beiser AS, Kase CS, Benjamin EJ, et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996;27:1760-4. http://dx.doi.org/10.1161/01. STR.27.10.1760
16. Wolfe CDA, Crichton SL, Heuschmann PU, McKevitt CJ, Toschke AM, Grieve AP, et al. Estimates of outcomes up to ten years after stroke: analysis from the prospective South London Stroke Register. PLoS Med 2011;8:e1001033. http://dx.doi.org/10.1371/journal.pmed.1001033
17. The Office of Health Economics (OHE). Estimating the direct costs of atrial fibrillation to the NHS in the constituent countries of the UK and at SHA level in England, 2008. London: OHE; 2009.
18. Stewart S, Murphy NF, Walker A, McGuire A, McMurray JJ. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart 2004;90:286-92. [Erratum published in Heart 2007;93:1472.] http://dx.doi.org/10.1136/hrt.2002.008748
19. Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007;69:546-54. http://dx.doi.org/10.1212/01. wnl.0000267275.68538.8d
20. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Int Med 2007;146:857-67.
21. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-51. http://dx.doi. org/10.1056/NEJMoa0905561
22. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-92. http://dx.doi. org/10.1056/NEJMoa1107039
23. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91. http://dx.doi.org/10.1056/ NEJMoa1009638
24. National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians; 2006. URL: http://guidance.nice.org.uk/CG36 (accessed 12 August 2010).
25. Gage BF, van WC, Pearce L, Hart RG, Koudstaal PJ, Boode BS, et al. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation 2004;110:2287-92. http://dx.doi.org/10.1161/01.CIR.0000145172.55640.93
26. Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Int Med 1994;154:1449-57. [Erratum published in Arch Intern Med 1994;154:2254.] http://dx.doi. org/10.1001/archinte.1994.00420130036007
27. Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Stroke 1999;30:1223-9. http:// dx.doi.org/10.1161/01.STR.30.6.1223
28. 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;285:2864-70. http://dx.doi.org/10.1001/jama.285.22.2864
29. Wang TJ, Massaro JM, Levy D, Vasan RS, Wolf PA, D'Agostino RB, et al. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. JAMA 2003;290:1049-56. http://dx.doi.org/10.1001/jama.290.8.1049
30. Becker RC, Meade TW, Berger PB, Ezekowitz M, O'Connor CM, Vorchheimer DA, et al. The primary and secondary prevention of coronary artery disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edn). Chest 2008;133(Suppl. 6):776-814.
31. Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. 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;137:263-72. http://dx.doi. org/10.1378/chest.09-1584
32. May AE, Geisler T, Gawaz M. Individualized antithrombotic therapy in high risk patients after coronary stenting. A double-edged sword between thrombosis and bleeding. Thromb Haemost 2008;99:487-93.
33. Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL, et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edn). Chest 2008;133(Suppl. 6):546-92.
34. Rubboli A, Halperin JL. Pro: 'Antithrombotic therapy with warfarin, aspirin and clopidogrel is the recommended regime in anticoagulated patients who present with an acute coronary syndrome and/or undergo percutaneous coronary interventions'. Thromb Haemost 2008;100:752-3.
35. Lip GY, Huber K, Andreotti F, Arnesen H, Airaksinen KJ, Cuisset T, et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/ or undergoing percutaneous coronary intervention/stenting. Thromb Haemost 2010;103:13-28. http://dx.doi.org/10.1160/TH09-08-0580
36. Rubboli A, Halperin JL, Airaksinen KE, Buerke M, Eeckhout E, Freedman SB, et al. Antithrombotic therapy in patients treated with oral anticoagulation undergoing coronary artery stenting. An expert consensus document with focus on atrial fibrillation. Ann Med 2008;40:428-36. http://dx.doi. org/10.1080/07853890802089786
37. Higgins JPT, Green Se. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 (updated March 2011). Copenhagen: The Cochrane Collaboration; 2011.
38. Khan KS, ter Riet G, Popay J, Nixon J, Kleijnen J. Conducting the review, Phase 5: Study quality and assessment. Centre for Reviews and Dissemination. Systematic reviews: CRD's guidance for undertaking reviews in health care. York: University of York; 2001. p. 11.
39. Pérez-Gómez F, Alegría E, Berjón J, Iriarte JA, Zumalde J, Salvador A, et al. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. J Am Coll Cardiol 2004;44:1557-66. http://dx.doi. org/10.1016/j.jacc.2004.05.084
40. Lidell C, Svedberg LE, Lindell P, Bandh S, Job B, Wallentin L. Clopidogrel and warfarin: absence of interaction in patients receiving long-term anticoagulant therapy for non-valvular atrial fibrillation. Thromb Haemost 2003;89:842-6.
41. Lechat P, Lardoux H, Mallet A, Sanchez P, Derumeaux G, Lecompte T, et al. Anticoagulant (fluindione)-aspirin combination in patients with high-risk atrial fibrillation. A randomized trial (Fluindione, Fibrillation Auriculaire, Aspirin et Contraste Spontane; FFAACS). Cerebrovasc Dis 2001;12:245-52. http://dx.doi.org/10.1159/000047711
42. Gullov AL, Koefoed BG, Petersen P, Pedersen TS, Andersen ED, Godtfredsen J, et al. Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study. Arch Int Med 1998;158:1513-21. http://dx.doi.org/10.1001/archinte.158.14.1513
43. 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. http://dx.doi.org/10.1016/ S0140-6736(96)03487-3
44. Pérez-Gómez F, Iriarte JA, Zumalde J, Berjón J, Salvador A, Alegría E, et al. Antithrombotic therapy in elderly patients with atrial fibrillation: effects and bleeding complications: a stratified analysis of the NASPEAF randomized trial. Eur Heart J 2007;28:996-1003. http://dx.doi.org/10.1093/eurheartj/ ehl364
45. Pérez-Gómez F, Salvador A, Zumalde J, Iriarte JA, Berjón J, Alegría E, et al. Effect of antithrombotic therapy in patients with mitral stenosis and atrial fibrillation: a sub-analysis of NASPEAF randomized trial. Eur Heart J 2006;27:960-7. http://dx.doi.org/10.1093/eurheartj/ehi667
46. Pérez-Gómez F, Fernandez C. Antiplatelet and anticoagulant therapy in patients with atrial fibrillation. Cardiol Rev 2006;23:44-8.
47. Gullov AL, Koefoed BG, Petersen P. Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation: the AFASAK 2 study. Atrial Fibrillation Aspirin and Anticoagulation. Arch Int Med 1999;159:1322-8. http://dx.doi.org/10.1001/archinte.159.12.1322
48. Hart RG, Pearce LA, Miller VT, Anderson DC, Rothrock JF, Albers GW, et al. Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies. Cerebrovasc Dis 2000;10:39-43. http://dx.doi. org/10.1159/000016023
49. Blackshear JL, Zabalgoitia M, Pennock G, Fenster P, Strauss R, Halperin J, et al. Warfarin safety and efficacy in patients with thoracic aortic plaque and atrial fibrillation. Am J Cardiol 1999;83:453-5. http://dx.doi.org/10.1016/S0002-9149(98)00886-8
50. Lopes RD, Elliott LE, White HD, Hochman JS, Van de WF, Ardissino D, et al. Antithrombotic therapy and outcomes of patients with atrial fibrillation following primary percutaneous coronary intervention: results from the APEX-AMI trial. Eur Heart J 2009;30:2019-28. http://dx.doi. org/10.1093/eurheartj/ehp213
51. Abdelhafiz AH, Wheeldon NM. Risk factors for bleeding during anticoagulation of atrial fibrillation in older and younger patients in clinical practice. Am J Geriatr Pharmacother 2008;6:1-11. http:// dx.doi.org/10.1016/j.amjopharm.2008.03.005
52. Toda G, Akiyama K, Sakuragawa K, Iliev II, Hayano M, Yano K. Thromboembolic complication in atrial fibrillation in a long-term follow-up: the relationship with underlying disease, type of atrial fibrillation, and antithrombotic therapy. Japanese Circ J 1998;62:255-60. http://dx.doi. org/10.1253/jcj.62.255
53. Albers GW, Yim JM, Belew KM, Bittar N, Hattemer CR, Phillips BG, et al. Status of antithrombotic therapy for patients with atrial fibrillation in university hospitals. Arch Int Med 1996;156:2311-16. http://dx.doi.org/10.1001/archinte.1996.00440190053006
54. Bover R, Perez-Gomez F, Maluenda MP, Asenjo S, Perez-Saldana R, Igea A, et al. Long-term follow-up of atrial fibrillation patients in the NASPEAF study. Prospective evaluation of different antiplatelet treatments. Rev Esp Cardiokl 2009;62:992-1000. http://dx.doi.org/10.1016/ S1885-5857(09)73265-7
55. Hart RG, Pearce LA, Rothbart RM, McAnulty JH, Asinger RW, Halperin JL. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol 2000;35:183-7. http://dx.doi.org/10.1016/ S0735-1097(99)00489-1
56. Suzuki S, Yamashita T, Kato T, Fujino T, Sagara K, Sawada H, et al. Incidence of major bleeding complication of warfarin therapy in Japanese patients with atrial fibrillation. Circ J 2007;71:761-5. http://dx.doi.org/10.1253/circj.71.761
57. Burton C, Isles C, Norrie J, Hanson R, Grubb E. The safety and adequacy of antithrombotic therapy for atrial fibrillation: a regional cohort study. Br J Gen Pract 2006;56:697-702.
58. Stenestrand U, Lindback J, Wallentin L, RIKS-HIA R. Anticoagulation therapy in atrial fibrillation in combination with acute myocardial infarction influences long-term outcome: a prospective cohort study from the Register of Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKS-HIA). Circulation 2005;112:3225-31. [Erratum published in Circulation 2006;113:e695.] http://dx.doi.org/10.1161/CIRCULATIONAHA.105.552984
59. Johnson CE, Lim WK, Workman BS. People aged over 75 in atrial fibrillation on warfarin: the rate of major hemorrhage and stroke in more than 500 patient-years of follow-up. J Am Geriatr Soc 2005;53:655-9. http://dx.doi.org/10.1111/j.1532-5415.2005.53215.x
60. Shireman TI, Howard PA, Kresowik TF, Ellerbeck EF. Combined anticoagulant-antiplatelet use and major bleeding events in elderly atrial fibrillation patients. Stroke 2004;35:2362-7. http://dx.doi. org/10.1161/01.STR.0000141933.75462.c2
61. Blich M, Gross B. Thromboembolic prophylaxis in nonrheumatic atrial fibrillation: utilization patterns, efficacy, and complications in a long-term follow-up of community patients. Int J Cardiol 2004;96:89-95. http://dx.doi.org/10.1016/j.ijcard.2003.06.014
62. Klein AL, Murray RD, Grimm RA, Li J, Person-Hansen C, Jasper SE, et al. Bleeding complications in patients with atrial fibrillation undergoing cardioversion randomized to transesophageal echocardiographically guided and conventional anticoagulation therapies. Am J Cardiol 2003;92:161-5. http://dx.doi.org/10.1016/S0002-9149(03)00531-9
63. Hansen ML, Sorensen R, Clausen MT, Fog-Petersen ML, Raunso J, Gadsboll N, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Int Med 2010;170:1433-41. http://dx.doi.org/10.1001/archinternmed.2010.271
64. 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;362:1691-8. http://dx.doi. org/10.1016/S0140-6736(03)14841-6
65. Albers GW, Diener HC, Frison L, Grind M, Nevinson M, Partridge S, et al. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 2005;293:690-8. http://dx.doi.org/10.1001/jama.293.6.690
66. Teitelbaum JS, von KR, Gjesdal K, Kristinsson A, Gahn G, Albers GW, et al. Effect of ximelagatran and warfarin on stroke subtypes in atrial fibrillation. Can J Neurol Sci 2008;35:160-5.
67. Akins PT, Feldman HA, Zoble RG, Newman D, Spitzer SG, Diener HC, et al. Secondary stroke prevention with ximelagatran versus warfarin in patients with atrial fibrillation: pooled analysis of SPORTIF III and V clinical trials. Stroke 2007;38:874-80. http://dx.doi.org/10.1161/01. STR.0000258004.64840.0b
68. White HD, Gruber M, Feyzi J, Kaatz S, Tse HF, Husted S, et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Int Med 2007;167:239-45. http://dx.doi.org/10.1001/archinte.167.3.239
69. Flaker GC, Gruber M, Connolly SJ, Goldman S, Chaparro S, Vahanian A, 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) trials. Am Heart J 2006;152:967-73. http://dx.doi.org/10.1016/j.ahj.2006.06.024
70. Douketis JD, Arneklev K, Goldhaber SZ, Spandorfer J, Halperin F, Horrow J. Comparison of bleeding in patients with nonvalvular atrial fibrillation treated with ximelagatran or warfarin: assessment of incidence, case-fatality rate, time course and sites of bleeding, and risk factors for bleeding. Arch Int Med 2006;166:853-9. http://dx.doi.org/10.1001/archinte.166.8.853
71. Halperin JL. Ximelagatran: oral direct thrombin inhibition as anticoagulant therapy in atrial fibrillation. J Am Coll Cardiol 2005;45:1-9. http://dx.doi.org/10.1016/j.jacc.2004.09.049
72. Bousser MG, Bouthier J, Buller HR, Cohen AT, Crijns H, Davidson BL, et al. 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. [Erratum published in Lancet 2008;372:2022.] http://dx.doi.org/10.1016/S0140-6736(08)60168-3
73. Ezekowitz MD, Reilly PA, Nehmiz G, Simmers TA, Nagarakanti R, Parcham-Azad K, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol 2007;100:1419-26. http://dx.doi.org/10.1016/j. amjcard.2007.06.034
74. Andersen LV, Vestergaard P, Deichgraeber P, Lindholt JS, Mortensen LS, Frost L. Warfarin for the prevention of systemic embolism in patients with non-valvular atrial fibrillation: a meta-analysis. Heart 2008;94:1607-13. http://dx.doi.org/10.1136/hrt.2007.135657
75. Garwood CL, Corbett TL. Use of anticoagulation in elderly patients with atrial fibrillation who are at risk for falls. Ann Pharmacother 2008;42:523-32. http://dx.doi.org/10.1345/aph.1K498
76. Hughes M, Lip GY, Guideline Development Group for the NICE national clinical guideline for management of atrial fibrillation in primary and secondary care. Risk factors for anticoagulationrelated bleeding complications in patients with atrial fibrillation: a systematic review. QJM 2007;100:599-607. http://dx.doi.org/10.1093/qjmed/hcm076
77. Dentali F, Douketis JD, Lim W, Crowther M. Combined aspirin-oral anticoagulant therapy compared with oral anticoagulant therapy alone among patients at risk for cardiovascular disease: a meta-analysis of randomized trials. Arch Int Med 2007;167:117-24. http://dx.doi.org/10.1001/ archinte.167.2.117
78. Cooper NJ, Sutton AJ, Lu G, Khunti K. Mixed comparison of stroke prevention treatments in individuals with nonrheumatic atrial fibrillation. Arch Int Med 2006;166:1269-75. http://dx.doi. org/10.1001/archinte.166.12.1269
79. Lip GY, Edwards SJ. Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis. Thrombosis Research 2006;118:321-33. http://dx.doi.org/10.1016/j.thromres.2005.08.007
80. Larson RJ, Fisher ES. Should aspirin be continued in patients started on warfarin? J Gen Int Med 2004;19:879-86. http://dx.doi.org/10.1111/j.1525-1497.2004.30419.x
81. Lip GY, Rothwell P, Sudlow C. Stroke prevention. Clin Evid 2004;12:253-84. [Update in Clin Evid 2005;14:173-97.]
82. McNamara RL, Tamariz LJ, Segal JB, Bass EB. Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography. Ann Int Med 2003;139:1018-33.
83. Perret-Guillaume C, Wahl DG. Low-dose warfarin in atrial fibrillation leads to more thromboembolic events without reducing major bleeding when compared to adjusted-dose: a meta-analysis. Thromb Haemost 2004;91:394-402.
84. Sanchez-Pena P, Lechat P. [Anticoagulant treatment in non-valvular atrial fibrillation.] Méd Thér 2002;8:277-84.
85. Segal JB, McNamara RL, Miller MR, Kim N, Goodman SN, Powe NR, et al. Prevention of thromboembolism in atrial fibrillation. A meta-analysis of trials of anticoagulants and antiplatelet drugs. J Gen Int Med 2000;15:56-67. http://dx.doi.org/10.1046/j.1525-1497.2000.04329.x
86. Aronow WS. Management of the older person with atrial fibrillation. J Am Geriatr Soc 1999;47:740-8.
87. Ezekowitz MD, Levine JA. Preventing stroke in patients with atrial fibrillation. JAMA 1999;281:1830-5. http://dx.doi.org/10.1001/jama.281.19.1830
88. Fera MS, Giovannini E. [Predictors of thromboembolic risk and role of antithrombolic prophylaxis in nonrheumatic atrial fibrillation.] G Ital Cardiol 1999;29:193-213.
89. Loewen P, Sunderji R, Gin K. The efficacy and safety of combination warfarin and ASA therapy: a systematic review of the literature and update of guidelines. Can J Cardiol 1998;14:717-26.
90. Howard PA, Duncan PW. Primary stroke prevention in nonvalvular atrial fibrillation: implementing the clinical trial findings. Ann Pharmacother 1997;31:1187-96.
91. Poli D, Antonucci E, Marcucci R, Mannini L, Falciani M, Abbate R, et al. The quality of anticoagulation on functional outcome and mortality for TIA/stroke in atrial fibrillation patients. Int J Cardiol 2009;132:109-13. http://dx.doi.org/10.1016/j.ijcard.2007.10.041
92. Connolly SJ, Pogue J, Eikelboom J, Flaker G, Commerford P, Franzosi MG, et al. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation 2008;118:2029-37. http://dx.doi.org/10.1161/CIRCULATIONAHA.107.750000
93. Landefeld CS, Anderson PA, Goodnough LT, Moir TW, Hom DL, Rosenblatt MW, et al. The bleeding severity index: Validation and comparison to other methods for classifying bleeding complications of medical therapy. J Clin Epidemiol 1989;42:711-18. http://dx.doi. org/10.1016/0895-4356(89)90066-8
94. Wan Y, Heneghan C, Perera R, Roberts N, Hollowell J, Glasziou P, et al. Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review. Circ Cardiovas Qual Outcomes 2008;1:84-91. http://dx.doi.org/10.1161/CIRCOUTCOMES.108.796185
95. Le-Kim L, Kerr D, Kelly A-M. Are patients on warfarin with high INR treated according to published guidelines? Int J Hematol 2009;5(1).
96. Singer DE, Hughes RA, Gress DR, Sheehan MA, Oertel LB, Ward MS, et al. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med 1990;323:1505-11. http://dx.doi.org/10.1056/NEJM199011293232201
97. Riley RD, Lambert PC, Abo-Zaid G. Meta-analysis of individual participant data: rationale, conduct, and reporting. BMJ 2010;340(c221).