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Antithrombotic treatment in patients with atrial fibrillation undergoing coronary angioplasty: rational convincement and supporting evidence

Published:February 13, 2020DOI:https://doi.org/10.1016/j.ejim.2020.02.004

      Highlights

      • Optimization of antithrombotic therapy in AF patients undergoing PCI is challenging.
      • Traditional triple therapy is associated with an excess risk of major bleeding events.
      • Recent RCTs showed a reduced risk of bleeding linked to DT.
      • Meta-analysis of RCTs arises the possibility of an increased risk of ST following DT.
      • DOACs is a valuable option, maintaining aspirin in higher thrombotic risk.

      Abstract

      Background

      The management of antithrombotic therapy in patients undergoing percutaneous coronary intervention (PCI) with an indication for long-term oral anticoagulant therapy (OAT) is still a matter of debate. We aim to evaluate the safety and the efficacy of dual therapy (DT) compared to triple therapy (TT) in this clinical setting.

      Methods

      A study level meta-analysis and a review of randomized trials selected using PubMed, Embase, EBSCO, Cochrane database of systematic reviews, Web of Science, and abstract from major cardiology congresses. Six randomized trials with 12,156 patients evaluating the strategy of DT vs. TT in patients treated with PCI with indication for long-term OAT were included.

      Results

      Patients treated with DT demonstrated a 45% relative reduction in the risk of TIMI major bleeding (1.71% vs. 2.99%; OR 0.55, 95% CI 0.41–0.71; P<0.0001) and TIMI minor bleeding compared to TT arm (4.67% vs 7.83%, OR 0.55 95% CI 0.39–0.78, P = 0.0007). All-cause mortality was similar in two arms (3.95% vs 3.77%, P = 0.92), as well as cardiovascular mortality (2.21% vs 2.19%, P = 0.97). DT was associated with a borderline increase of ST (1.02% vs 0.67%, P = 0.07). No significant differences were observed in occurrence of MI and stroke.

      Conclusions

      Our findings suggest that DT is safer than TT with regard to occurrence of major bleeding. DT with a direct oral anticoagulant plus clopidogrel at discharge could be effective in most patients, maintaining aspirin in periprocedural phase and as longer “tailored” treatment for patients at higher ischemic risk.

      Keywords

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      References

        • Boriani G.
        • Proietti M.
        Screening for atrial fibrillation: need for an integrated, structured approach.
        Eur J Intern Med. 2019; 67: 33-35
        • Proietti M.
        • Laroche C.
        • Nieuwlaat R.
        • Crijns H.J.G.M.
        • Maggioni A.P.
        • Lane D.A.
        • et al.
        Lip GYH; EORP-AF general pilot registry; Euro heart survey on AF investigators. increased burden of comorbidities and risk of cardiovascular death in atrial fibrillation patients in Europe over ten years: a comparison between EORP-AF pilot and EHS-AF registries.
        Eur J Intern Med. 2018; 55: 28-34
        • Pérez-Gómez F.
        • Alegría E.
        • Berjón J.
        • 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. 2004; 44: 1557-1566
        • Wang T.Y.
        • Robinson L.A.
        • Ou F.S.
        • et al.
        Discharge antithrombotic strategies among patients with acute coronary syndrome previously on warfarin anticoagulation: physician practice in the CRUSADE registry.
        Am Heart J. 2008; 155: 361-368
        • Valgimigli M.
        • Bueno H.
        • Byrne R.A.
        • et al.
        ESC focused update on dual antiplatelet therapy in coronary artery diseasedeveloped in collaboration with EACTS: the task force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS).
        Eur Heart J. 2017; (2017)
      1. ACTIVE writing group of the active investigators. 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. 2006; 367: 1903-1912
        • Paikin J.S.
        • Wright D.S.
        • Crowther M.A.
        • Mehta S.R.
        • Eikelboom J.W.
        Triple antithrombotic therapy in patients with atrial fibrillation and coronary artery stents.
        Circulation. 2010; 121: 2067-2070
        • Neumann F.J.
        • Sousa-Uva M.
        • Ahlsson A.
        • et al.
        ESC Scientific document group. 2018 ESC/EACTS guidelines on myocardial revascularization.
        Eur Heart J. 2019; 40: 87-165
        • Knuuti J.
        • Wijns W.
        • Saraste A.
        • Capodanno D.
        • Barbato E.
        • Funck-Brentano C.
        • Prescott E.
        • Storey R.F.
        • Deaton C.
        • Cuisset T.
        • Agewall S.
        • Dickstein K.
        • Edvardsen T.
        • Escaned J.
        • Gersh B.J.
        • Svitil P.
        • Gilard M.
        • Hasdai D.
        • Hatala R.
        • Mahfoud F.
        • Masip J.
        • Muneretto C.
        • Valgimigli M.
        • Achenbach S.
        • Bax J.J.
        • ESC Scientific Document Group
        ESC guidelines for the diagnosis and management of chronic coronary syndromes.
        Eur Heart J. 2019; (2019 Aug 31)https://doi.org/10.1093/eurheartj/ehz425
        • Angiolillo D.J.
        • Goodman S.G.
        • Bhatt D.L.
        • et al.
        Antithrombotic therapy in patients with atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary intervention.
        Circulation. 2018; 138: 527-536
        • Lopes R.D.
        • Heizer G.
        • Aronson R.
        • et al.
        AUGUSTUS investigators. antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation.
        N Engl J Med. 2019; (Mar 17)https://doi.org/10.1056/NEJMoa1817083
        • Vranckx P.
        • Valgimigli M.
        • Eckardt L.
        • Tijssen J.
        • Lewalter T.
        • Gargiulo G.
        • Batushkin V.
        • Campo G.
        • Lysak Z.
        • Vakaliuk I.
        • Milewski K.
        • Laeis P.
        • Reimitz P.E.
        • Smolnik R.
        • Zierhut W.
        • Goette A
        Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial.
        Lancet. 2019; https://doi.org/10.1016/S0140-6736(19)31872-0
        • Fiedler K.A.
        • Maeng M.
        • Mehilli J.
        • et al.
        Duration of triple therapy in patients requiring oral anticoagulation after drug-eluting stent implantation: the ISAR-TRIPLE trial.
        J Am Coll Cardiol. 2015; 65: 1619-1629
        • DerSimonian R.
        • Laird N
        Meta-analysis in clinical trials.
        Control Clin Trials. 1986; 7: 177-188
        • Higgins J.P.T.
        • Thompson S.G.
        • Deeks J.J.
        • Altman D.G
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Begg C.B.
        • Mazumdar M
        Operating characteristics of a rank correlation test for publication bias.
        Biometrics. 1994; 50: 1088-1101
        • Dewilde W.J.M.
        • Oirbans T.
        • Verheugt F.W.A.
        • 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.
        Lancet. 2013; 381: 1107-1115
        • Gibson C.M.
        • Mehran R.
        • Bode C.
        • et al.
        Prevention of bleeding in patients with atrial fibrillation undergoing PCI.
        N Engl J Med. 2016; 375: 2423-2434
        • Cannon C.P.
        • Bhatt D.L.
        • Oldgren J.
        • et al.
        REDUAL PCI steering committee and investigators. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation.
        N Engl J Med. 2017; 377: 1513-1524
        • D'Ascenzo F.
        • Taha S.
        • Moretti C.
        • et al.
        Meta-analysis of randomized controlled trials and adjusted observational results of use of clopidogrel, aspirin, and oral anticoagulants in patients undergoing percutaneous coronary intervention.
        Am J Cardiol. 2015; 115: 1185-1193
        • Lamberts M.
        • Olesen J.B.
        • Ruwald M.H.
        • et al.
        Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study.
        Circulation. 2012; 126: 1185-1193
        • Ndrepepa G.
        • Neumann F.J.
        • Richardt G.
        • et al.
        Prognostic value of access and non-access sites bleeding after percutaneous coronary intervention.
        Circ Cardiovasc Interv. 2013; 6: 354-361
        • Lamberts M.
        • Gislason G.H.
        • Olesen J.B.
        • et al.
        Oral anticoagulation and antiplatelets in atrial fibrillation patients after myocardial infarction and coronary intervention.
        J Am Coll Cardiol. 2013; 62: 981-989
        • Hess C.N.
        • Peterson E.D.
        • Peng S.A.
        • et al.
        Use and outcomes of triple therapy among older patients with acute myocardial infarction and atrial fibrillation.
        J Am Coll Cardiol. 2015; 66: 616-627
        • Rubboli A.
        And now we have the AUGUSTUS … How will it impact on antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention?.
        Eur J Intern Med. 2019; 65: 1-3
        • Harskamp R.E.
        • Alexander J.H.
        • Lopes R.D.
        Navigating the treacherous waters of antithrombotic therapies in patients with atrial fibrillation and coronary artery disease: lessons from AUGUSTUS.
        Eur J Intern Med. 2019; 65: 4-5
        • Cavallari I.
        • Patti G
        Meta-Analysis comparing the safety and efficacy of dual versus triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.
        Am J Cardiol. 2018; 121: 718-724
        • Golwala H.B.
        • Cannon C.P.
        • Steg P.G.
        • et al.
        Safety and efficacy of dual vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials.
        Eur Heart J. 2018; 39: 1726-1735
        • Fortuni F.
        • Ferlini M.
        • Leonardi S.
        • Angelini F.
        • Crimi G.
        • Somaschini A.
        • et al.
        Dual versus triple therapy in patients on oral anticoagulants and undergoing coronary stent implantation: a systematic review and meta-analysis.
        Int J Cardiol. 2018; 273: 80-87
        • Agarwal N.
        • Mahmoud A.N.
        • Mojadidi M.K.
        • Golwala H.
        • Elgendy I.Y
        Dual versus triple antithrombotic therapy in patients undergoing percutaneous coronary intervention-meta-analysis and meta-regression.
        Cardiovasc Revasc Med. 2019; https://doi.org/10.1016/j.carrev.2019.02.022
        • Lopes R.D.
        • Hong H.
        • Harskamp R.E.
        • Bhatt D.L.
        • Mehran R.
        • Cannon C.P.
        • et al.
        Safety and efficacy of antithrombotic strategies in patients with atrial fibrillation undergoing percutaneous coronary intervention: a network meta-analysis of randomized controlled trials.
        JAMA Cardiol. 2019; (Jun 19)https://doi.org/10.1001/jamacardio.2019.1880
        • Potpara T.S.
        • Mujovic N.
        • Proietti M.
        • Dagres N.
        • Hindricks G.
        • Collet J.P.
        • Valgimigli M.
        • Heidbuchel H.
        • Lip G.Y.H
        Revisiting the effects of omitting aspirin in combined antithrombotic therapies for atrial fibrillation and acute coronary syndromes or percutaneous coronary interventions: meta-analysis of pooled data from the PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS trials.
        Europace. 2019 Oct 11; (pii: euz259)https://doi.org/10.1093/europace/euz259
        • Sullivan A.E.
        • Nanna M.G.
        • Rao S.V.
        • Cantrell S.
        • Gibson C.M.
        • Verheugt F.W.A.
        • Peterson E.D.
        • Lopes R.D.
        • Alexander J.H.
        • Granger C.B.
        • Yee M.K.
        • Kong D.F
        A systematic review of randomized trials comparing double versus triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.
        Catheter Cardiovasc Interv. 2019; (Nov 11)https://doi.org/10.1002/ccd.28535
        • Gargiulo G.
        • Goette A.
        • Tijssen J.
        • Eckardt L.
        • Lewalter T.
        • Vranckx P.
        • Valgimigli M
        Safety and efficacy outcomes of double vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of non-vitamin K antagonist oral anticoagulant-based randomized clinical trials.
        Eur Heart J. 2019 Dec 7; 40: 3757-3767https://doi.org/10.1093/eurheartj/ehz732
        • Bavry A.A.
        • Bhatt D.L
        Appropriate use of drug-eluting stents: balancing the reduction in restenosis with the concern of late thrombosis.
        Lancet. 2008; 371: 2134-2143
        • Bhatt D.L.
        • Hirsch A.T.
        • Ringleb P.A.
        • Hacke W.
        • Topol E.J
        Reduction in the need for hospitalization for recurrent ischemic events and bleeding with clopidogrel instead of aspirin.
        CAPRIE investigators. Am Heart J. 2000; 140: 67-73
        • Hurlen M.
        • Abdelnoor M.
        • Smith P.
        • Erikssen J.
        • Arnesen H
        Warfarin, aspirin, or both after myocardial infarction.
        N Engl J Med. 2002; 347: 969-974
        • Es R.F.
        • van Jonker J.J.C.
        • Verheugt F.W.A.
        • Deckers J.W.
        • Grobbee D.E
        Antithrombotics in the secondary prevention of events in coronary thrombosis-2 (ASPECT-2) research group. Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial.
        Lancet. 2002; 360: 109-113