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Antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting: Suggested strategies tailored to an integrated evaluation of different risk profiles

Published:March 29, 2017DOI:https://doi.org/10.1016/j.ejim.2017.03.017
      The optimal antithrombotic therapy for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention with stent (PCI-S) is still undetermined [
      • Patti G.
      • Di Sciascio G.
      Antithrombotic strategies in patients on oral anticoagulant therapy undergoing percutaneous coronary intervention: a proposed algorithm based on individual risk stratification.
      ,
      • Holmes Jr., D.R.
      • Kereiakes D.J.
      • Kleiman N.S.
      • Moliterno D.J.
      • Patti G.
      • Grines C.L.
      Combining antiplatelet and anticoagulant therapies.
      ]. Current recommendations, however generally based on a level of evidence C (i.e. derived from experts' opinion and/or non-randomized, small-size data), suggest triple therapy (TT) with either a vitamin K-antagonist (VKA) or non-vitamin K antagonist oral anticoagulant (NOAC) plus aspirin and clopidogrel as the preferred strategy to prevent both thromboembolic and ischemic cardiac events [
      • Lip G.Y.
      • Windecker S.
      • Huber K.
      • Kirchhof P.
      • Marin F.
      • Ten Berg J.M.
      • et al.
      Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS).
      ,
      • Heidbuchel H.
      • Verhamme P.
      • Alings M.
      • Antz M.
      • Diener H.C.
      • Hacke W.
      • et al.
      Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation.
      ]. Owing to the well documented increase in bleeding complications of TT and the high safety (with no apparent impaired efficacy) of dual therapy (DT) with VKA plus clopidogrel reported in the WOEST trial [
      • Dewilde W.J.
      • Oirbans T.
      • Verheugt F.W.
      • Kelder J.C.
      • De Smet B.J.
      • Herrman J.P.
      • et al.
      WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial.
      ], this latter regimen, possibly also to be extended to NOACs, may be considered in patients at increased bleeding risk and concomitant no significant elevation of ischemic cardiac risk [
      • Lip G.Y.
      • Windecker S.
      • Huber K.
      • Kirchhof P.
      • Marin F.
      • Ten Berg J.M.
      • et al.
      Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS).
      ,
      • Heidbuchel H.
      • Verhamme P.
      • Alings M.
      • Antz M.
      • Diener H.C.
      • Hacke W.
      • et al.
      Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation.
      ]. The recent publication of the PIONEER AF-PCI trial [
      • Gibson C.M.
      • Mehran R.
      • Bode C.
      • Halperin J.
      • Verheugt F.W.
      • Wildgoose P.
      • et al.
      Prevention of bleeding in patients with atrial fibrillation undergoing PCI.
      ] has provided additional evidence on the management of antithrombotic therapy in patients with AF undergoing PCI-S, also investigating for the first time a NOAC, namely rivaroxaban, being part of the combined antithrombotic therapy for this specific setting of patients. In the PIONEER AF-PCI trial, patients were randomized to receive DT with rivaroxaban 15 mg/day and a P2Y12 inhibitor, essentially clopidogrel, or TT with either very low dose rivaroxaban (2.5 mg twice/day) or warfarin (target International Normalized Ratio 2.0–3.0) plus aspirin and clopidogrel. The results of the PIONEER AF-PCI trial indicated a significantly lower bleeding risk in both arms receiving rivaroxaban, where the intensity of the antithrombotic treatment was reduced either because only one antiplatelet agent was given or the dose of the anticoagulant as part of TT was extremely low. Of note, the 15 mg daily dose of rivaroxaban is lower than that used in the ROCKET-AF trial [
      • Patel M.R.
      • Mahaffey K.W.
      • Garg J.
      • Pan G.
      • Singer D.E.
      • Hacke W.
      • ROCKET AF Investigators
      • et al.
      Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.
      ], in which rivaroxaban was given at the dose of 20 mg (reduced to 15 mg only in presence of creatinine clearance 30–49 ml/min), and resulted at least non-inferior to warfarin in preventing thromboembolic complications, with similar major bleeding rates and significant decrease of intracranial hemorrhages. Moreover, the ATLAS-2 trial [
      • Mega J.L.
      • Braunwald E.
      • Wiviott S.D.
      • Bassand J.P.
      • Bhatt D.L.
      • Bode C.
      • ATLAS ACS 2–TIMI 51 Investigators
      • et al.
      Rivaroxaban in patients with a recent acute coronary syndrome.
      ], performed on patients with acute coronary syndrome, demonstrated lower incidence of cardiovascular events and cardiovascular death with rivaroxaban 2.5 mg twice a day compared to placebo on top of dual antiplatelet therapy.

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