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

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.2–4 The safety of triple therapy is undoubtedly an issue, since a relevant incidence of both minor and major bleedings has been reported.2–4 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 6–12 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 2.0–3.0, 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 2.0–2.5) OAC plus aspirin or high-intensity (INR 3.0–4.0) 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 2.0–3.0) OAC in the secondary prevention of coronary artery disease.7