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Cardiovascular Drugs and Therapy

, Volume 32, Issue 2, pp 191–196 | Cite as

Contemporary Antithrombotic Treatment in Patients with Non-valvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: Rationale and Design of the Greek AntiPlatElet Atrial Fibrillation (GRAPE-AF) Registry

  • Ioanna Xanthopoulou
  • Vasiliki-Maria Dragona
  • Periklis Davlouros
  • Costas Tsioufis
  • Efstathios Iliodromitis
  • Dimitrios Alexopoulos
  • for the GRAPE-AF Investigators
ORIGINAL ARTICLE
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Abstract

Background

Approximately 5 to 7% of patients undergoing percutaneous coronary intervention (PCI) for the treatment of coronary artery disease require chronic oral anticoagulation (OAC) on top of aspirin and a P2Y12 receptor antagonist, mainly due to non-valvular atrial fibrillation (AF). The advent of non-vitamin K antagonist oral anticoagulants (NOACs) increased treatment options, while there is cumulative evidence that dual combination of a NOAC and a P2Y12 receptor antagonist attenuates risk of bleeding, compared to traditional triple therapy, consisting of a vitamin K antagonist (VKA), aspirin, and a P2Y12 receptor antagonist, without significantly compromising efficacy.

Study Design

Greek AntiPlatElet Atrial Fibrillation (GRAPE-AF, NCT 03362788) is an observational, nationwide study of non-valvular AF patients undergoing PCI, planning to enroll over 1-year period > 500 participants in 25 tertiary and non-tertiary PCI centers in Greece. Key data to be collected pre-discharge include demographics, detailed past medical history, and antithrombotic and concomitant treatment. Patients will be followed up at 1, 6, and 12 months post hospital discharge. Αt each follow-up visit, data on antithrombotic treatment, ischemic, bleeding, and adverse events will be collected. Study’s primary endpoint is clinically significant bleeding (Bleeding Academic Research Consortium, BARC ≥ 2) at 12 months, between VKAs and NOACs-treated patients, analyzed using Cox proportional hazards models, by an intention-to-treat principle. An independent endpoint committee will adjudicate all clinical events.

Conclusions

This study aims at providing “real-world” information on current antithrombotic treatment patterns and clinical outcome of patients with non-valvular AF undergoing PCI.

Keywords

Antithrombotic treatment Atrial fibrillation Percutaneous coronary intervention 

Notes

Funding Information

This study has been funded by the Hellenic Cardiological Society.

Compliance with Ethical Standards

Conflict of Interest

Dr. Alexopoulos discloses lecturing honoraria from AstraZeneca, Bayer, and Boehringer Ingelheim and Advisory Board fees from AstraZeneca, Bayer, Boehringer Ingelheim, and Medtronic. Dr. Tsioufis has received consultancy fees, Research Grant and, honoraria fees from the following: Servier, Menarini, Medtronic, Bayer, Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer, Chiesi, Recordati, Sanofi, and MSD. The rest of the authors have nothing to disclose.

Ethical Approval

This article does not contain any studies with animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

  1. 1.
    Rossini R, Musumeci G, Lettieri C, Molfese M, Mihalcsik L, Mantovani P, et al. Long-term outcomes in patients undergoing coronary stenting on dual oral antiplatelet treatment requiring oral anticoagulant therapy. Am J Cardiol. 2008;102(12):1618–23.CrossRefPubMedGoogle Scholar
  2. 2.
    Rubboli A, Colletta M, Valencia J, Capecchi A, Franco N, Zanolla L, et al. Periprocedural management and in-hospital outcome of patients with indication for oral anticoagulation undergoing coronary artery stenting. J Interv Cardiol. Google Scholar
  3. 3.
    Choi HI, Ahn JM, Kang SH, Lee PH, Kang SJ, Lee SW, et al. Prevalence, management, and long-term (6-year) outcomes of atrial fibrillation among patients receiving drug-eluting coronary stents. JACC Cardiovasc Interv. Google Scholar
  4. 4.
    Lopes RD, Pieper KS, Horton JR, Al-Khatib SM, Newby LK, Mehta RH, et al. Short- and long-term outcomes following atrial fibrillation in patients with acute coronary syndromes with or without ST-segment elevation. Heart. 2008;94(7):867–73.CrossRefPubMedGoogle Scholar
  5. 5.
    Rene AG, Genereux P, Ezekowitz M, Kirtane AJ, Xu K, Mehran R, et al. Impact of atrial fibrillation in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention (from the HORIZONS-AMI [harmonizing outcomes with revascularization and stents in acute myocardial infarction] trial). Am J Cardiol. 2014;113(2):236–42.CrossRefPubMedGoogle Scholar
  6. 6.
    Alexopoulos D, Vlachakis P, Lekakis J. Triple antithrombotic therapy in atrial fibrillation patients undergoing PCI: a fading role. Cardiovasc Drugs Ther. 2017;31(3):319–24.CrossRefPubMedGoogle Scholar
  7. 7.
    Agarwal N, Jain A, Mahmoud AN, Bishnoi R, Golwala H, Karimi A, et al. Safety and efficacy of dual versus triple antithrombotic therapy in patients undergoing percutaneous coronary intervention. Am J Med. 2017;130(11):1280–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Zhu W, Guo L, Liu F, Wan R, Shen Y, Lip GYH, et al. Efficacy and safety of triple versus dual antithrombotic therapy in atrial fibrillation and ischemic heart disease: a systematic review and meta-analysis. Oncotarget. 2017;8(46):81154–66.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51.CrossRefPubMedGoogle Scholar
  10. 10.
    Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.CrossRefPubMedGoogle Scholar
  11. 11.
    Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.CrossRefPubMedGoogle Scholar
  12. 12.
    Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–104.CrossRefPubMedGoogle Scholar
  13. 13.
    Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375(25):2423–34.CrossRefPubMedGoogle Scholar
  14. 14.
    Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. 2017;377(16):1513–24.CrossRefPubMedGoogle Scholar
  15. 15.
    Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Alfonso F, Macaya C, Bass TA, et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol. 2007;49(14):1505–16.CrossRefPubMedGoogle Scholar
  16. 16.
    Stone GW, Witzenbichler B, Weisz G, Rinaldi MJ, Neumann FJ, Metzger DC, et al. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet. 2013;382(9892):614–23.CrossRefPubMedGoogle Scholar
  17. 17.
    Bhatt DL. O PIONEERs! The beginning of the end of full-dose triple therapy with warfarin? Circulation. 2017;135(4):334–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893–962.CrossRefPubMedGoogle Scholar
  19. 19.
    Macle L, Cairns J, Leblanc K, Tsang T, Skanes A, Cox JL, et al. 2016 Focused update of the canadian cardiovascular society guidelines for the management of atrial fibrillation. Can J Cardiol. 2016;32(10):1170–85.CrossRefPubMedGoogle Scholar
  20. 20.
    Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016;68(10):1082–115.CrossRefPubMedGoogle Scholar
  21. 21.
    Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, et al. 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. 2018;39(3):213–60.CrossRefPubMedGoogle Scholar
  22. 22.
    Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123(23):2736–47.CrossRefPubMedGoogle Scholar
  23. 23.
    Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093–100.CrossRefPubMedGoogle Scholar
  24. 24.
    Fang MC, Go AS, Chang Y, Borowsky LH, Pomernacki NK, Udaltsova N, et al. A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol. 2011;58(4):395–401.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    O’Brien EC, Simon DN, Thomas LE, Hylek EM, Gersh BJ, Ansell JE, et al. The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation. Eur Heart J. 2015;36(46):3258–64.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137(2):263–72.CrossRefPubMedGoogle Scholar
  27. 27.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.CrossRefPubMedGoogle Scholar
  28. 28.
    Alexopoulos D, Stavrou K, Koniari I, Gkizas V, Perperis A, Kontoprias K, et al. Ticagrelor vs prasugrel one-month maintenance therapy: impact on platelet reactivity and bleeding events. Thromb Haemost. 2014;112(3):551–7.PubMedGoogle Scholar
  29. 29.
    Dewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, Herrman JP, et al. 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(9872):1107–15.CrossRefPubMedGoogle Scholar
  30. 30.
    Gao F, Shen H, Wang ZJ, Yang SW, Liu XL, Zhou YJ. Rationale and design of the RT-AF study: combination of rivaroxaban and ticagrelor in patients with atrial fibrillation and coronary artery disease undergoing percutaneous coronary intervention. Contemp Clin Trials. 2015;43:129–32.CrossRefPubMedGoogle Scholar
  31. 31.
    Lu W, Chen L, Wang Y, Yao Y, Fu C, Zuo P, et al. Rationale and design of MANJUSRI trial: a randomized, open-label, active-controlled multicenter study to evaluate the safety of combined therapy with ticagrelor and warfarin in AF subjects after PCI-eS. Contemp Clin Trials. 2015;40:166–71.CrossRefPubMedGoogle Scholar
  32. 32.
    Braun OO, Bico B, Chaudhry U, Wagner H, Koul S, Tyden P, et al. Concomitant use of warfarin and ticagrelor as an alternative to triple antithrombotic therapy after an acute coronary syndrome. Thromb Res. 2015;135(1):26–30.CrossRefPubMedGoogle Scholar
  33. 33.
    Sarafoff N, Martischnig A, Wealer J, Mayer K, Mehilli J, Sibbing D, et al. Triple therapy with aspirin, prasugrel, and vitamin K antagonists in patients with drug-eluting stent implantation and an indication for oral anticoagulation. J Am Coll Cardiol. 2013;61(20):2060–6.CrossRefPubMedGoogle Scholar
  34. 34.
    Jackson LR 2nd, Ju C, Zettler M, Messenger JC, Cohen DJ, Stone GW, et al. Outcomes of patients with acute myocardial infarction undergoing percutaneous coronary intervention receiving an oral anticoagulant and dual antiplatelet therapy: a comparison of clopidogrel versus prasugrel from the TRANSLATE-ACS Study. JACC Cardiovasc Interv. 2015;8(14):1880–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ioanna Xanthopoulou
    • 1
  • Vasiliki-Maria Dragona
    • 2
  • Periklis Davlouros
    • 1
  • Costas Tsioufis
    • 3
  • Efstathios Iliodromitis
    • 4
  • Dimitrios Alexopoulos
    • 4
  • for the GRAPE-AF Investigators
  1. 1.Cardiology DepartmentPatras University HospitalPatrasGreece
  2. 2.3rd Department of Internal MedicineRed Cross HospitalAthensGreece
  3. 3.1st Department of Cardiology, Ippokration HospitalNational and Capodistrian University of Athens Medical SchoolAthensGreece
  4. 4.2nd Department of Cardiology, Attikon University HospitalNational and Capodistrian University of Athens Medical SchoolAthensGreece

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