Journal Information
Vol. 30. Issue 12.
Pages 905-924 (December 2011)
Share
Share
Download PDF
More article options
Vol. 30. Issue 12.
Pages 905-924 (December 2011)
Review article
Open Access
Antithrombotic therapy in nonvalvular atrial fibrillation: A narrative review
Terapêutica anti-trombótica na fibrilação auricular não-valvular: uma revisão narrativa
Visits
6336
Susana P.D. Sáa, Rui P. Rodriguesb, João Santos-Antunesc, Francisco Rocha Gonçalvesa, José Pedro L. Nunesa,
Corresponding author
jplnunes@med.up.pt

Corresponding author.
a Faculdade de Medicina, Universidade do Porto, Porto, Portugal
b Serviço de Medicina Interna, Hospital São João, Porto, Portugal
c Serviço de Gastroenterologia, Hospital São João, Porto, Portugal
This item has received

Under a Creative Commons license
Article information
Abstract

Atrial fibrillation (AF) is an important and potentially modifiable cause of stroke. It has been known since 1989 that oral anticoagulant drugs, such as warfarin, lead to a dramatic decrease in stroke associated with AF. The best risk-benefit ratio is obtained with intensity of oral anticoagulant treatment for an INR of 2-3, even in the elderly. Given the risks of anticoagulant therapy, including bleeding, individual thromboembolic risk must be assessed in patients with AF. In 2009, dabigatran was shown to be a reasonable alternative to vitamin K antagonists, establishing itself as a major alternative to warfarin in AF patients. Rivaroxaban and apixaban have subsequently also been shown to be alternatives to warfarin. When there are contraindications to vitamin K antagonists, antiplatelet agents can produce a therapeutic effect, although much less than oral anticoagulants. Apixaban may be a better alternative to aspirin in this setting. Patients with low-risk atrial fibrillation (no risk factors) have not been the subjects of specific clinical trials. It is unclear what would be the best therapeutic choice for these patients.

Keywords:
Atrial fibrillation
Warfarin
Aspirin
Dabigatran
Rivaroxaban
Apixaban
Resumo

A fibrilacao auricular (FA) e uma causa importante e potencialmente modificavel do acidente vascular cerebral. Desde 1989 que se encontra demonstrado que o uso de anti-coagulantes orais, como a varfarina, se associa a uma reducao dramatica da incidencia de acidente vascular cerebral associado a FA. A intensidade da anticoagulacao oral com uma melhor relacao risco-beneficio e obtida com urn INR de 2-3, mesmo no paciente idoso. Tendo em consideracao os riscos da anticoagulacao oral, incluindo as hemorragias, e necessario estimar o risco tromboembolico individual nos doentes com FA. Em 2009, o dabigatrano mostrou ser uma alternativa razoavel aos antagonistas da vitamina K - vindo a estabelecer-se como uma alternativa importante a varfarina em doentes com FA. Foi subsequentemente demonstrado que quer o rivaroxabano quer o apixabano tern urn estatuto semelhante ao dabigatrano, enquanto alternativas importantes a varfarina. Quando existam contra-indicacoes a terapeutica com antagonistas da vitamina K, os antiplaquetarios podem produzir urn efeito terapeutico, sem duvida urn efeito muito menos importante do que os anticoagulantes orais. 0 apixabano podera ser uma alternativa preferivel a aspirina neste contexto. Os doentes com FA de “baixo risco” (sem factores de risco) nao foram estudados em ensaios clinicos levados a cabo especificamente para esta situacao. E pouco claro qual e a melhor alternativa terapeutica nestes doentes.

Palavras-chave:
Fibrilacao auricular
Varfarina
Aspirina
Dabigatrano
Rivaroxabano
Apixabano
Full text is only aviable in PDF
References
[1]
A.J. Camm, P. Kirchhof, G.Y.H. Lip, et al.
Guidelines for the management of atrial fibrillation.
Eur Heart J., 31 (2010), pp. 2369-2429
[2]
D.M. Lloyd-Jones, T.J. Wang, E.P. Leip, et al.
Lifetime risk for development of atrial fibrillation.
The Framingham Heart Study. Circulation., 110 (2004), pp. 1042-1046
[3]
J. Friberg, P. Buch, H. Scharling, et al.
Rising rates of hospital admissions for atrial fibrillation.
Epidemiology., 14 (2003), pp. 666-672
[4]
J. Heeringa, D.A.M. van der Kuip, A. Hofman, et al.
Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study.
Eur Heart J., 27 (2006), pp. 949-953
[5]
D. Bonhorst, M. Mendes, P. Adragao, et al.
Prevalencia de fibrilhacao auricular na populacao portuguesa com 40 ou mais anos.
Estudo FAMA. Rev Port Cardiol., 29 (2010), pp. 331-350
[6]
P.A. Wolf, R.D. Abbott, W.B. Kannel.
Atrial fibrillation as an independent risk factor for stroke: the Framingham Study.
Stroke., 22 (1991), pp. 983-988
[7]
W.E. Wysokinski, N. Ammash, F. Sobande, et al.
Predicting left atrial thrombi in atrial fibrillation.
Am Heart J., 159 (2010), pp. 665-671
[8]
Stroke Risk in Atrial Fibrillation Working Group.
Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation.
[9]
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 Intern Med. 1994;154:1449-57.
[10]
P. Petersen, J. Godtfredsen, G. Boysen, et al.
Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK Study.
Lancet., 333 (1989), pp. 175-179
[11]
The Boston Area Anticoagulation Trial for Atrial Fibrillation investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl JMed. 1990;323:1505-11.
[12]
Stroke Prevention in Atrial Fibrillation investigators. Stroke prevention in atrial fibrillation study. Final results. Circulation. 1991;84:527-39.
[13]
S.J. Connolly, A. Laupacis, M. Gent, et al.
Canadian Atrial Fibrillation Anticoagulation (CAFA) study.
J Am Coll Cardiol., 18 (1991), pp. 349-355
[14]
M.D. Ezekowitz, S.L. Bridgers, K.E. James, et al.
Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators.
N Engl J Med., 327 (1992), pp. 1406-1412
[15]
EAFT (European Atrial Fibrillation Trial) Study Group. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet. 1993;342:1255-62.
[16]
Stroke Prevention in Atrial Fibrillation Investigators. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet. 1994;343:687-91.
[17]
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.
[18]
C. Morocutti, G. Amabile, F. Fattapposta, et al.
Indobufen versus warfarin in the secondary prevention of major vascular events in nonrheumatic atrial fibrillation. SIFA (Studio Italiano Fibrillazione Atriale) Investigators.
Stroke., 28 (1997), pp. 1015-1021
[19]
A.L. Gulløv, B.G. Koefoed, P. Petersen, 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 Intern Med., 158 (1998), pp. 1513-1521
[20]
A.L. Gulløv, B.G. Koefoed, P. Petersen.
Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation.
The AFASAK 2 Study. Arch Intern Med., 159 (1999), pp. 1322-1328
[21]
V. Pengo, A. Zasso, F. Barbero, et al.
Effectiveness of fixed minidose warfarin in the prevention of thromboembolic and vascular death in nonrheumatic atrial fibrillation.
Am J Cardiol., 82 (1998), pp. 433-437
[22]
B.S.P. Hellemons, M. Langenberg, J. Lodder, et al.
Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin.
BMJ., 319 (1999), pp. 958-964
[23]
T. Yamaguchi.
Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial fibrillation: a multicenter, prospective, randomized trial.
Stroke., 31 (2000), pp. 817-821
[24]
N. Edvardsson, S. Juul-Moller, R. Omblus, et al.
Effects of low-dose warfarin and aspirin versus no treatment on stroke in a medium-risk patient population with atrial fibrillation.
J Intern Med., 254 (2003), pp. 95-101
[25]
F. Perez-Gomez, E. Alegria, J. Berjon, 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., 44 (2004), pp. 1557-1566
[26]
Executive Steering Committee on behalf of the SPORTIF III Investigators. Stroke prevention with the oral direct throm-bin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet. 2003;362:1691-8.
[27]
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.
[28]
S. Connolly, J. Pogue, R. Hart, 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., 367 (2006), pp. 1903-1912
[29]
D.Y. Hu, H.P. Zhang, Y.H. Sun, et al.
The randomized study of efficiency and safety of antithrombotic therapy in nonvalvular atrial fibrillation: warfarin compared with aspirin.
Zhonghua Xin Xue Guan Bing Za Zhi., 34 (2006), pp. 295-298
[30]
J. Mant, F.D. Hobbs, K. Fletcher, 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).
Lancet., 370 (2007), pp. 493-503
[31]
A. Rash, T. Downes, R. Portner, et al.
A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO).
Age Ageing., 36 (2007), pp. 151-156
[32]
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.
[33]
S.J. Connolly, M.D. Ezekowitz, S. Yusuf, et al.
Dabigatran versus warfarin in patients with atrial fibrillation.
N Engl J Med., 361 (2009), pp. 1139-1151
[34]
S.J. Connolly, M.D. Ezekowitz, S. Yusuf, et al.
Newly identified events in the RE-LY trial.
N Engl J Med., 363 (2010), pp. 1875-1876
[35]
L. Wallentin, S. Yusuf, M.D. Ezekowitz, et al.
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., 376 (2010), pp. 975-983
[36]
M.R. Patel, K.W. Mahaffey, J. Garg, et al.
Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.
N Engl J Med., 365 (2011), pp. 883-891
[37]
C.B. Granger, J.H. Alexander, J.J.V. McMurray, et al.
Apixaban versus warfarin in patients with atrial fibrillation.
N Engl J Med., 365 (2011), pp. 981-992
[38]
The SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators. Patients with nonvalvular atrial fibrillation at low risk of stroke during treatment with aspirin: Stroke Prevention in Atrial Fibrillation III Study. JAMA. 1998;279:1273-7.
[39]
I.S. Posada, V. Barriales.
Alternate-day dosing of aspirin in atrial fibrillation.
Am Heart J., 138 (1999), pp. 137-143
[40]
Japan Atrial Fibrillation Stroke Trial Group. Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial. Stroke. 2006;37:447-51.
[41]
R.G. Hart, D.L. Bhatt, W. Hacke, et al.
Clopidogrel and aspirin versus aspirin alone for the prevention of stroke in patients with a history of atrial fibrillation: subgroup analysis of the CHARISMA randomized trial.
Cerebrovasc Dis., 25 (2008), pp. 344-347
[42]
S.J. Connolly, J. Pogue, R.G. Hart, et al.
Effect of clopidogrel added to aspirin in patients with atrial fibrillation.
N Engl J Med., 360 (2009), pp. 2066-2078
[43]
S.J. Connolly, J. Eikelboom, C. Joyner, et al.
Apixaban in patients with atrial fibrillation.
N Engl J Med., 364 (2011), pp. 806-817
[44]
R.G. Hart, L.A. Pearce, Ml. Aguilar.
Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation.
Ann Intern Med., 146 (2007), pp. 857-867
[45]
C. Van Walraven, R.G. Hart, D.E. Singer, et al.
Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis.
JAMA., 288 (2002), pp. 2441-2448
[46]
G.Y.H. Lip, S.J. Edwards.
Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis.
Thromb Res., 118 (2006), pp. 321-333
[47]
Aguilar M, Hart R. Antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database Syst Rev. 2005:CD001925.
[48]
Aguilar M, Hart R. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database Syst Rev. 2005:CD001927.
[49]
F.C. Taylor, H. Cohen, S. Ebrahim.
Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation.
BMJ., 322 (2001), pp. 321-326
[50]
L.K. Gottlieb, S. Salem-Schatz.
Anticoagulation in atrial fibrillation.
Does efficacy in clinical trials translate into effectiveness in practice?. Arch Intern Med., 154 (1994), pp. 1945-1953
[51]
L. Kalra, G. Yu, I. Perez, et al.
Prospective cohort study to determine if trial efficacy of anticoagulation for stroke prevention in atrial fibrillation translates into clinical effectiveness.
BMJ., 320 (2000), pp. 1236-1239
[52]
J.J. Caro, K.M. Flegel, M.E. Orejuela, et al.
Anticoagulant prophylaxis against stroke in atrial fibrillation: effectiveness in actual practice.
CMAJ., 161 (1999), pp. 493-497
[53]
A. Evans, L. Kalra.
Are the results of randomized controlled trials on anticoagulation in patients with atrial fibrillation gen-eralizable to clinical practice?.
Arch Intern Med., 161 (2001), pp. 1443-1447
[54]
A.S. Go, E.M. Hylek, Y. Chang, et al.
Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice?.
JAMA., 290 (2003), pp. 2685-2692
[55]
E.M. Hylek, A.S. Go, Y. Chang, et al.
Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation.
N Engl J Med., 349 (2003), pp. 1019-1026
[56]
S. Rietbrock, J.M. Plumb, A.M. Gallagher, et al.
How effective are dose-adjusted warfarin and aspirin for the prevention of stroke in patients with chronic atrial fibrillation?.
An analysis of the UK General Practice Research Database. Thromb Haemost., 101 (2009), pp. 527-534
[57]
S. Ederhy, G. Dufaitre, L. Boyer-Chatenet, et al.
Should all patients with non-valvular atrial fibrillation be anticoagulated?.
IntJCardiol., 143 (2010), pp. 8-15
[58]
R.G. Hart, L.A. Pearce, R. McBride, et al.
Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF l-lll clinical trials.
The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Stroke., 30 (1999), pp. 1223-1229
[59]
G. Boysen, J. Nyboe, M. Appleyard, et al.
Stroke incidence and risk factors for stroke in Copenhagen.
Denmark. Stroke., 19 (1988), pp. 1345-1353
[60]
B.F. Gage, C. van Walraven, L. Pearce, et al.
Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin.
Circulation., 110 (2004), pp. 2287-2292
[61]
R.S. Epstein, T.P. Moyer, R.E. Aubert, et al.
Warfarin geno-typing reduces hospitalization rates.
J Am Coll Cardiol., 55 (2010), pp. 2804-2812
[62]
B.N. Beasley, E.F. Unger, R. Temple.
Anticoagulant options - why the FDA approved a higher but not a lower dose of dabigatran.
N Engl J Med., 364 (2011), pp. 1788-1790
[63]
L.M. Mega.
A new era for anticoagulation in atrial fibrillation.
N Engl J Med., 365 (2011), pp. 1052-1105
[64]
G.Y.H. Lip, R. Nieuwlaat, R. Pisters, et al.
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., 137 (2010), pp. 263-272
[65]
D.R. Holmes, V.Y. Reddy, Z.G. Turi, et al.
Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial.
Lancet., 374 (2009), pp. 534-542
Copyright © 2011. Sociedade Portuguesa de Cardiologia
Idiomas
Revista Portuguesa de Cardiologia (English edition)
Article options
Tools
en pt

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos

By checking that you are a health professional, you are stating that you are aware and accept that the Portuguese Journal of Cardiology (RPC) is the Data Controller that processes the personal information of users of its website, with its registered office at Campo Grande, n.º 28, 13.º, 1700-093 Lisbon, telephone 217 970 685 and 217 817 630, fax 217 931 095, and email revista@spc.pt. I declare for all purposes that the information provided herein is accurate and correct.