European Heart Journal Advance Access originally published online on October 30, 2006
European Heart Journal 2006 27(23):2908-2909; doi:10.1093/eurheartj/ehl348
The combination of anticoagulant and anti-platelet therapy in patients with atrial fibrillation: a comment on the recent ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation
Cardiac Catheterization Laboratory
Division of Cardiology
Maggiore Hospital
Largo Nigrisoli 2
40133 Bologna
Italy
Tel: +39 516478976
Fax: +39 516478635
E-mail address: andrearubboli{at}libero.it
Division of ardiology
Maggiore Hospital
Largo Nigrisoli 2
40133 Bologna
Italy
In the recently published guidelines,1 all the aspects concerning the management of patients with atrial fibrillation are extensively and exhaustively discussed. Several assertions about the combination of anticoagulant and platelet-inhibitor therapy, however, appear questionable. First, a prominent role of clopidogrel in itself for the maintenance of coronary and stent patency can hardly be asserted because of the lack of specific evidence-based data. Instead, dual blockage of the ADP- and cyclooxygenase-mediated pathways of platelet aggregation, as obtained by the combined administration of clopidogrel and aspirin, is known to be necessary for optimal prevention of coronary artery thrombosis after an acute coronary syndrome or stent implantation. Therefore, the ideal antithrombotic treatment after coronary artery stenting in patients with atrial fibrillation appears to be represented by the combination of dual antiplatelet treatment and oral anticoagulation (OAC), rather than the suggested association of clopidogrel and OAC.1 Indeed, in small observational studies including patients with an indication for OAC undergoing coronary stent implantation, such triple therapy has been shown highly effective in totally preventing thrombo-embolic and thrombotic events, both at short- and long-term follow-up.24 The safety of triple therapy is undoubtedly an issue, since a relevant incidence of both minor and major bleedings has been reported.24 The occurrence of major bleedings at 30 days, however, turned out to be associated with advanced age, excessive anticoagulation, presence of organic lesions of the digestive tract, or traumatism,2,3 therefore suggesting that triple therapy might indeed be safe, provided careful monitoring of the intensity of anticoagulation is carried out, screening for conditions predisposing to bleeding is properly performed, and elderly patients are excluded. Since the prolongation of triple therapy has been associated with the occurrence of (late) major bleedings,4 it appears prudent to keep such treatment as short as possible. Thus, the implantation of drug-eluting stents should be avoided as much as possible because of the need for a 612 months course of dual antiplatelet treatment. Finally, in patients deemed at very high haemorrhagic risk, the combination of aspirin only and OAC probably represents a reasonable option, in conjunction, however, with the implantation of less thrombogenic (e.g. carbon- or heparin-coated) stents, which, in small, albeit prospectively evaluated, observational series, have been associated with an extremely low 30-day incidence of adverse cardiac events when aspirin-alone therapy was given.5,6
Also questionable is the assertion that patients with atrial fibrillation who had coronary stent implantation should receive lifelong warfarin monotherapy, since OAC alone, targeted at an International Normalized Ratio (INR) of 2.03.0, provides satisfactory antithrombotic prophylaxis against both cerebral and myocardial ischaemic events.1 On the contrary, current evidence is in support of either the combination of moderate-intensity (INR 2.02.5) OAC plus aspirin or high-intensity (INR 3.04.0) OAC alone, which have shown comparable efficacy on the composite of death, myocardial infarction, or stroke, whereas no conclusive data are available at present on the efficacy of moderate-intensity (INR 2.03.0) OAC in the secondary prevention of coronary artery disease.7
References
- Fuster V, Rydèn 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, Tamargo JL, Zamorano JL. (2006) 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 and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Manangement of Patients with Atrial Fibrillation). Eur Heart J 27:19792030.
[Free Full Text] - Orford JL, Fasseas P, Melby S, Burger K, Steinhubl SR, Holmes DR, Berger PB. (2004) Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation. Am Heart J 147:463467.[CrossRef][Web of Science][Medline]
- Rubboli A, Colletta M, Sangiorgio P, Di Pasquale G. (2004) Antithrombotic strategies in patients with an indication for long-term anticoagulation undergoing coronary artery stenting: safety and efficacy data from a single center. Ital Heart J 5:919925.[Medline]
- Khurram Z, Chou E, Minutello R, Bergman G, Parikh M, Naidu S, Wong SC, Hong MK. (2006) Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding. J Invasive Cardiol 18:162164.[Medline]
- Bartorelli AL, Trabattoni D, Montorsi P, Fabbiocchi F, Galli S, Ravagnani P, Grancini L, Cozzi S, Loaldi A. (2002) Aspirin alone antiplatelet regimen after intracoronary placement of the CarbostentTM: The Antares Study. Cathet Cardiovasc Interv 55:150156.[CrossRef][Web of Science][Medline]
- Mehran R, Aymong ED, Ashby DT, Fischell T, Whitworth H Jr, Siegel R, Thomas W, Wong SC, Narasimaiah R, Lansky AJ, Leon MB. (2003) Safety of an aspirin-alone regimen after intracoronary stenting with a heparin-coated stent. Final results of the HOPE (HEPACOAT and an antithrombotic regimen of aspirin alone) Study. Circulation 108:10781083.
- Husted SE, Ziegler BK, Kher A. (2006) Long-term anticoagulant therapy in patients with coronary artery disease. Eur Heart J 27:913919.
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