Published online before print August 23, 2007, doi: 10.1161/STROKEAHA.107.492488
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(Stroke. 2007;38:e107.)
© 2007 American Heart Association, Inc.
Letters to the Editor |
Combining Antiplatelet Drugs and Oral Anticoagulant Therapy in Atrial Fibrillation: Acute Coronary Syndromes and/or Percutaneous Coronary Intervention/Stenting Revisited
University Department of Medicine, City Hospital, Birmingham, UK
To the Editor:
We agree with Gorelick1 that there is little evidence that combination aspirin and oral anticoagulant (OAC) therapy among patients with atrial fibrillation (AF) improves stroke prevention but, instead, increases risk of major bleeding. The latter should come as little surprise, given the mode of action of both drugs.
Indeed, the efficacy of OAC compared with aspirin in this condition is overwhelmingly supported by data from clinical trials.2 However, AF commonly associates with (cardio)vascular disease, and frequently AF patients are still prescribed both OAC and antiplatelet therapies in combination. In the setting of AF and acute coronary syndromes (ACS) or coronary angioplasty/stents, it is not infrequent for patients to be prescribed ‘triple therapy’ with OAC, aspirin and clopidogrel.
Gorelick1 provides a critique on the recent article by Flaker et al,3 but broad similar conclusions were reported from the FFAACS trial,4 where fluindione (an OAC) plus aspirin was compared with fluindione alone, and no difference in thromboembolism rate was reported between the 2 arms, although combination therapy did significantly increase bleeding rate (13.1% versus 1.2%, P=0.003).
Given the rising prevalence of AF and coexistent vascular disease, as well as increasing application of percutaneous coronary angioplasty/stenting, the coprescription of OAC and antiplatelet agents is likely to surge. The ACC/AHA/ESC 2006 Guidelines for the Management of Patients with AF5 suggest that after angioplasty/stenting, low-dose aspirin (<100 mg/d) and/or clopidogrel (75 mg/d) may be given concurrently with anticoagulation to prevent myocardial ischemic events, but acknowledges these strategies have not been thoroughly evaluated and are associated with an increased risk of bleeding. These recommendations do not give a differential management strategy in relation to an ACS presentation or the perceived bleeding risk.
Given recent concerns over late stent thrombosis with drug eluting stents, the likelihood of some AF patients at high risk of stroke being coprescribed OAC plus aspirin plus clopidogrel for 12 months (or more) by some cardiologists is real, with the associated high bleeding risk.6 Other practical management guidance for AF patients presenting with ACS and/or need angioplasty/stenting have tried to relate the approach to stroke risk, associated ACS presentation, bleeding risk and/or type of stent used7 (Table). The choice of warfarin plus clopidogrel long-term5,7 may seem an ‘evidence free’ zone, but given data demonstrating that the combination of OAC plus aspirin is inadequate to prevent coronary stent thrombosis,7,8 and that OAC alone is marginally different from ‘OAC plus aspirin’ in ACS for reducing coronary events but increases bleeding,7,9 more prospective data are urgently required.
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Clearly, a very careful balance is needed between stroke prevention (especially in a ‘high risk’ AF patient requiring OAC), recurrent cardiac ischemia (eg, post-ACS and/or stent use) and bleeding risk attributed to adding antiplatelet therapy to OAC use.
Acknowledgments
Disclosures
None.
References
1. Gorelick PB. Combining aspirin with oral anticoagulant therapy: is this a safe and effective practice in patients with atrial fibrillation. Stroke. 2007; 38: 1652–1654.
2. Lip GYH, Edwards SJ. Stroke prevention with aspirin, warfarin and xilmelagatran in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis. Thromb Res. 2006; 118: 321–333.[CrossRef][Medline] [Order article via Infotrieve]
3. Flaker GC, Gruber M, Connolly SJ, Goldman S, Chaparro S, Vahanian A, Halinen MO, Horrow J, Halperin JL; SPORTIF Investigators. 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: 967–973.[CrossRef][Medline] [Order article via Infotrieve]
4. Lechat P, Lardoux H, Mallet A, Sanchez P, Derumeaux G, Lecompte T, Maillard L, Mas JL, Mentre F, Pousset F, Lacomblez L, Pisica G, Solbes-Latourette S, Raynaud P, Chaumet-Riffaud P; FFAACS (Fluindione, Fibrillation Auriculaire, Aspirin et Contraste Spontane) Investigators. 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: 245–252.[CrossRef][Medline] [Order article via Infotrieve]
5. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey J-Y, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S, Smith SC, Jacobs AK, Adams CD, Anderson JL, Antman EM, Hunt SA, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc J-J, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Zamorano JL. 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). J Am Coll Cardiol. 2006; 48: e149–246.
6. Khurram Z, Chou E, Minutello R, Bergman G, Parikh M, Naidu S, Wong SC, Hong MK. Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding. J Invasive Cardiol. 2006; 18: 162–164.[Medline] [Order article via Infotrieve]
7. Lip GY, Karpha M. Anticoagulant and antiplatelet therapy use in patients with atrial fibrillation undergoing percutaneous coronary intervention: the need for consensus and a management guideline. Chest. 2006; 130: 1823–1827.
8. Karjalainen PP, Porela P, Ylitalo A, Vikman S, Nyman K, Vaittinen MA, Airaksinen TJ, Niemela M, Vahlberg T, Airaksinen KE. Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting. Eur Heart J. 2007; 28: 726–732.
9. Lip GYH, Varma C. Anticoagulation plus aspirin following acute myocardial infarction: Yes or no. and if the latter, why not? Thromb Res. 2006; 118: 429–432.[CrossRef][Medline] [Order article via Infotrieve]
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