Clinical Research in Cardiology

, Volume 107, Issue 7, pp 533–538 | Cite as

Antithrombotic therapy in patients with non-valvular atrial fibrillation undergoing percutaneous coronary intervention: should we change our practice after the PIONEER AF-PCI and RE-DUAL PCI trials?

  • D. Duerschmied
  • J. Brachmann
  • H. Darius
  • N. Frey
  • H. A. Katus
  • W. Rottbauer
  • A. Schäfer
  • H. Thiele
  • C. Bode
  • Uwe Zeymer
Critical Perspective
  • 587 Downloads

Abstract

The number of patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) is increasing. Since these patients have a CHA2DS2-VASc score of 1 or higher, they should be treated with oral anticoagulation to prevent stroke. However, combination therapy with oral anticoagulation for prevention of embolic stroke and dual platelet inhibition for prevention of coronary thrombosis significantly increases bleeding complications. The optimal combination, intensity and duration of antithrombotic combination therapy is still not known. In the rather small randomized WOEST trial, the combination of a vitamin K antagonist (VKA) and clopidogrel decreased bleeding compared to the conventional triple therapy with VKA, clopidogrel and aspirin. In the PIONEER AF-PCI trial, two rivaroxaban-based treatment regimens significantly reduced bleeding complications compared to conventional triple therapy without increasing embolic or ischemic complications following PCI. Dual therapy with rivaroxaban and clopidogrel appeared to provide an optimal risk–benefit ratio. In the RE-DUAL PCI trial, dual therapy with dabigatran also reduced bleeding complications compared to conventional triple therapy. With respect to the composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization dabigatran-based dual therapy was non-inferior to VKA-based triple therapy. The upcoming trials AUGUSTUS with apixaban and ENTRUST-PCI with edoxaban will further examine the use of NOACs in this setting. While recent guidelines recommend NOAC-based dual therapy in only a subset of patients (those who are at increased risk of bleeding), the available data now suggest that this should be the preferred choice for the majority of patients. Adding aspirin to this primary choice for up to 4 weeks in patients at especially high ischemic risk would likely prevent atherothrombotic events, but this needs further investigation. Taken together, it is time to adjust our practice and move to dual therapy consisting of a NOAC plus clopidogrel in most patients.

Keywords

Oral anticoagulation Percutaneous coronary intervention Atrial fibrillation Bleedings 

Notes

Compliance with ethical standards

Conflict of interest

Duerschmied D: Speaker honoraria from Bayer, Daiichi-Sankyo, Pfizer, Brachmann J: none, Darius H: Speaker’s honoraria and consulting fees from Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, Boehringer Ingelheim, Frey N: none, Katus HA: none, Rottbauer W: none, Schäfer A: Speaker honoraria from Daiichi, Bristol-Myers Squibb/Pfizer; Consulting fees from Bayer, Boehringer Ingelheim, Thiele H: none, Bode C: Research grants from Bayer, GlaxoSmithKline, Merck; Speaker’s honoraria from Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, Boehringer Ingelheim; Consulting fees from Bayer, Zeymer U: Speaker’s honoraria and consulting fees from Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, Boehringer Ingelheim.

References

  1. 1.
    Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, Birmingham M, Ianus J, Burton P, van Eickels M, Korjian S, Daaboul Y, Lip GY, Cohen M, Husted S, Peterson ED, Fox KA (2016) Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med 375(25):2423–2434.  https://doi.org/10.1056/NEJMoa1611594 CrossRefPubMedGoogle Scholar
  2. 2.
    Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, Maeng M, Merkely B, Zeymer U, Gropper S, Nordaby M, Kleine E, Harper R, Manassie J, Januzzi JL, Ten Berg JM, Steg PG, Hohnloser SH, Investigators R-DPSCa (2017) Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med 377(16):1513–1524.  https://doi.org/10.1056/NEJMoa1708454 CrossRefPubMedGoogle Scholar
  3. 3.
    Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K (2016) 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37(38):2893–2962.  https://doi.org/10.1093/eurheartj/ehw210 CrossRefPubMedGoogle Scholar
  4. 4.
    Leon MB, Baim DS, Popma JJ, Gordon PC, Cutlip DE, Ho KK, Giambartolomei A, Diver DJ, Lasorda DM, Williams DO, Pocock SJ, Kuntz RE (1998) A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 339(23):1665–1671.  https://doi.org/10.1056/NEJM199812033392303 CrossRefPubMedGoogle Scholar
  5. 5.
    Authors/Task Force M, Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S (2015) 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J.  https://doi.org/10.1093/eurheartj/ehv320 Google Scholar
  6. 6.
    Authors/Task F, Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A (2014) 2014 ESC/EACTS guidelines on myocardial revascularization: the Task Force on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 35(37):2541–2619.  https://doi.org/10.1093/eurheartj/ehu278 CrossRefGoogle Scholar
  7. 7.
    Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van’t Hof A, Widimsky P, Zahger D (2012) ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 33(20):2569–2619.  https://doi.org/10.1093/eurheartj/ehs215 pii].CrossRefPubMedGoogle Scholar
  8. 8.
    Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, Advisors (2016) Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J.  https://doi.org/10.1093/eurheartj/ehw058 PubMedGoogle Scholar
  9. 9.
    Moser M, Olivier CB, Bode C (2013) Triple antithrombotic therapy in cardiac patients: more questions than answers. Eur Heart J.  https://doi.org/10.1093/eurheartj/eht461 Google Scholar
  10. 10.
    Lamberts M, Olesen JB, Ruwald MH, Hansen CM, Karasoy D, Kristensen SL, Kober L, Torp-Pedersen C, Gislason GH, Hansen ML (2012) 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 126(10):1185–1193.  https://doi.org/10.1161/CIRCULATIONAHA.112.114967 CrossRefPubMedGoogle Scholar
  11. 11.
    Proietti M, Airaksinen KEJ, Rubboli A, Schlitt A, Kiviniemi T, Karjalainen PP, Lip GYH, Group AS (2017) Synergic impact of oral anticoagulation control and renal function in determining major adverse events in atrial fibrillation patients undergoing percutaneous coronary intervention: insights from the AFCAS registry. Clin Res Cardiol 106(6):420–427.  https://doi.org/10.1007/s00392-016-1071-0 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ruile P, Jander N, Blanke P, Schoechlin S, Reinohl J, Gick M, Rothe J, Langer M, Leipsic J, Buettner HJ, Neumann FJ, Pache G (2017) Course of early subclinical leaflet thrombosis after transcatheter aortic valve implantation with or without oral anticoagulation. Clin Res Cardiol 106(2):85–95.  https://doi.org/10.1007/s00392-016-1052-3 CrossRefPubMedGoogle Scholar
  13. 13.
    Proietti M, Nobili A, Raparelli V, Napoleone L, Mannucci PM, Lip GY, investigators R (2016) Adherence to antithrombotic therapy guidelines improves mortality among elderly patients with atrial fibrillation: insights from the REPOSI study. Clin Res Cardiol 105(11):912–920.  https://doi.org/10.1007/s00392-016-0999-4 CrossRefPubMedGoogle Scholar
  14. 14.
    Fauchier L, Clementy N, Bisson A, Stamboul K, Ivanes F, Angoulvant D, Babuty D, Lip GY (2017) Prognosis in patients with atrial fibrillation and a presumed “temporary cause” in a community-based cohort study. Clin Res Cardiol 106(3):202–210.  https://doi.org/10.1007/s00392-016-1040-7 CrossRefPubMedGoogle Scholar
  15. 15.
    Gunawardene M, Willems S, Schaffer B, Moser J, Akbulak RO, Jularic M, Eickholt C, Nuhrich J, Meyer C, Kuklik P, Sehner S, Czerner V, Hoffmann BA (2017) Influence of periprocedural anticoagulation strategies on complication rate and hospital stay in patients undergoing catheter ablation for persistent atrial fibrillation. Clin Res Cardiol 106(1):38–48.  https://doi.org/10.1007/s00392-016-1021-x CrossRefPubMedGoogle Scholar
  16. 16.
    Seeger J, Bothner C, Dahme T, Gonska B, Scharnbeck D, Markovic S, Rottbauer W, Wohrle J (2016) Efficacy and safety of percutaneous left atrial appendage closure to prevent thromboembolic events in atrial fibrillation patients with high stroke and bleeding risk. Clin Res Cardiol 105(3):225–229.  https://doi.org/10.1007/s00392-015-0910-8 CrossRefPubMedGoogle Scholar
  17. 17.
    Stahli BE, Gebhard C, Gick M, Ferenc M, Mashayekhi K, Buettner HJ, Neumann FJ, Toma A (2017) Outcomes after percutaneous coronary intervention for chronic total occlusion according to baseline renal function. Clin Res Cardiol.  https://doi.org/10.1007/s00392-017-1179-x Google Scholar
  18. 18.
    De Caterina R, Lip GYH (2017) The non-vitamin K antagonist oral anticoagulants (NOACs) and extremes of body weight-a systematic literature review. Clin Res Cardiol 106(8):565–572.  https://doi.org/10.1007/s00392-017-1102-5 CrossRefPubMedGoogle Scholar
  19. 19.
    Hohnloser SH, Basic E, Nabauer M (2017) Comparative risk of major bleeding with new oral anticoagulants (NOACs) and phenprocoumon in patients with atrial fibrillation: a post-marketing surveillance study. Clin Res Cardiol 106(8):618–628.  https://doi.org/10.1007/s00392-017-1098-x CrossRefPubMedGoogle Scholar
  20. 20.
    Dewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, Herrman JP, Adriaenssens T, Vrolix M, Heestermans AA, Vis MM, Tijsen JG, van’t Hof AW, ten Berg JM, Investigators Ws (2013) 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 381(9872):1107–1115.  https://doi.org/10.1016/S0140-6736(12)62177-1 CrossRefPubMedGoogle Scholar
  21. 21.
    Fiedler KA, Maeng M, Mehilli J, Schulz-Schupke S, Byrne RA, Sibbing D, Hoppmann P, Schneider S, Fusaro M, Ott I, Kristensen SD, Ibrahim T, Massberg S, Schunkert H, Laugwitz KL, Kastrati A, Sarafoff N (2015) Duration of triple therapy in patients requiring oral anticoagulation after drug-eluting stent implantation: the ISAR-TRIPLE trial. J Am Coll Cardiol 65(16):1619–1629.  https://doi.org/10.1016/j.jacc.2015.02.050 CrossRefPubMedGoogle Scholar
  22. 22.
    Lip GY, Windecker S, Huber K, Kirchhof P, Marin F, Ten Berg JM, Haeusler KG, Boriani G, Capodanno D, Gilard M, Zeymer U, Lane D, Document R, Storey RF, Bueno H, Collet JP, Fauchier L, Halvorsen S, Lettino M, Morais J, Mueller C, Potpara TS, Rasmussen LH, Rubboli A, Tamargo J, Valgimigli M, Zamorano JL (2014) 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). Eur Heart J 35(45):3155–3179.  https://doi.org/10.1093/eurheartj/ehu298 CrossRefPubMedGoogle Scholar
  23. 23.
    Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S, Baumgartner H, Gaemperli O, Achenbach S, Agewall S, Badimon L, Baigent C, Bueno H, Bugiardini R, Carerj S, Casselman F, Cuisset T, Erol C, Fitzsimons D, Halle M, Hamm C, Hildick-Smith D, Huber K, Iliodromitis E, James S, Lewis BS, Lip GY, Piepoli MF, Richter D, Rosemann T, Sechtem U, Steg PG, Vrints C, Luis Zamorano J (2016) 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 37(3):267–315.  https://doi.org/10.1093/eurheartj/ehv320 CrossRefPubMedGoogle Scholar
  24. 24.
    Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Juni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN, Group ESCSD., Guidelines ESCCfP, Societies ESCNC. (2017) 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed 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.  https://doi.org/10.1093/eurheartj/ehx419 PubMedCentralGoogle Scholar
  25. 25.
    Gibson CM, Pinto DS, Chi G, Arbetter D, Yee M, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, Burton P, van Eickels M, Korjian S, Daaboul Y, Jain P, Lip GY, Cohen M, Peterson ED, Fox KA (2017) Recurrent hospitalization among patients with atrial fibrillation undergoing intracoronary stenting treated with 2 treatment strategies of rivaroxaban or a dose-adjusted oral vitamin K antagonist treatment strategy. Circulation 135(4):323–333.  https://doi.org/10.1161/CIRCULATIONAHA.116.025783 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Mega JL, Braunwald E, Wiviott SD, Bassand JP, Bhatt DL, Bode C, Burton P, Cohen M, Cook-Bruns N, Fox KA, Goto S, Murphy SA, Plotnikov AN, Schneider D, Sun X, Verheugt FW, Gibson CM (2012) Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 366(1):9–19.  https://doi.org/10.1056/NEJMoa1112277 CrossRefPubMedGoogle Scholar
  27. 27.
    Schoener L, Jellinghaus S, Richter B, Pfluecke C, Ende G, Christoph M, Quick S, Loehn T, Speiser U, Poitz DM, Mierke J, Strasser RH, Ibrahim K (2017) Reversal of the platelet inhibitory effect of the P2Y12 inhibitors clopidogrel, prasugrel, and ticagrelor in vitro: a new approach to an old issue. Clin Res Cardiol 106(11):868–874.  https://doi.org/10.1007/s00392-017-1128-8 CrossRefPubMedGoogle Scholar
  28. 28.
    Ohman EM, Roe MT, Steg PG, James SK, Povsic TJ, White J, Rockhold F, Plotnikov A, Mundl H, Strony J, Sun X, Husted S, Tendera M, Montalescot G, Bahit MC, Ardissino D, Bueno H, Claeys MJ, Nicolau JC, Cornel JH, Goto S, Kiss RG, Guray U, Park DW, Bode C, Welsh RC, Gibson CM (2017) Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial. Lancet.  https://doi.org/10.1016/S0140-6736(17)30751-1 Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • D. Duerschmied
    • 1
  • J. Brachmann
    • 2
  • H. Darius
    • 3
  • N. Frey
    • 4
  • H. A. Katus
    • 5
  • W. Rottbauer
    • 6
  • A. Schäfer
    • 7
  • H. Thiele
    • 8
  • C. Bode
    • 1
  • Uwe Zeymer
    • 9
  1. 1.Cardiology and Angiology I, Faculty of Medicine, Heart CenterUniversity of FreiburgFreiburgGermany
  2. 2.Department of Cardiology, Angiology, and Pneumology, Second Medical ClinicCoburg HospitalCoburgGermany
  3. 3.Department of Cardiology, Vascular Medicine and Intensive Care MedicineVivantes Neukoelln Medical CentreBerlinGermany
  4. 4.Department of Cardiology and AngiologyUniversity of KielKielGermany
  5. 5.Department of Internal Medicine IIIUniversity of HeidelbergHeidelbergGermany
  6. 6.Department of Internal Medicine II, Cardiology, Angiology, PneumologyUniversity of UlmUlmGermany
  7. 7.Department of Cardiology and AngiologyHannover Medical SchoolHanoverGermany
  8. 8.Department of Internal Medicine/CardiologyHeart Center Leipzig - UniversityHospitalLeipzigGermany
  9. 9.Klinikum Ludwigshafen and Institut für HerzinfarktforschungLudwigshafen/RheinGermany

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