Download PDF
Hamostaseologie 2022; 42(03): 201-209
DOI: 10.1055/a-1606-7523
Review Article

Non–Vitamin K Antagonist Oral Anticoagulants in Coronary Artery Disease

Samer Al Said
1   Department of Internal Medicine III Cardiology Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany
2   DZHK (German Centre for Cardiovascular Research), University of Heidelberg, Heidelberg/Mannheim, Germany
,
Michael Ellscheid
1   Department of Internal Medicine III Cardiology Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany
,
Eleftherios T. Beltsios
3   Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
,
Norbert Frey
1   Department of Internal Medicine III Cardiology Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany
2   DZHK (German Centre for Cardiovascular Research), University of Heidelberg, Heidelberg/Mannheim, Germany
› Author Affiliations Funding None.
› Further Information
Also available at
   Permissions and Reprints

Abstract

The prevention of atherothrombotic events is the primary goal in the treatment of patients with arteriosclerotic disorders. Despite recent improvements in the management of coronary artery disease (CAD) with revascularization techniques and antiplatelet therapy, some patients remain at risk of recurrent cardiovascular events. This could be related to additional thrombin generation. As a result, there has been interest in developing novel therapies to prevent thromboembolic events, targeting thrombin-mediated pathways. These include non–vitamin K antagonist oral anticoagulants (NOACs). This article aims to summarize the recent clinical studies that investigated the role of NOACs in CAD.

Zusammenfassung

Die Prävention atherothrombotischer Ereignisse ist das primäre Ziel bei der Behandlung von Patienten mit arteriosklerotischen Erkrankungen. Trotz aktueller Fortschritte bei der Behandlung der koronaren Herzkrankheit mit Revaskularisationstechniken und Thrombozytenaggregationshemmung leiden einige Patienten weiterhin unter kardiovaskulären ischämischen Ereignissen. Dies könnte mit einer übermäßigen Thrombinbildung zusammenhängen. Infolgedessen bestand Interesse an der Entwicklung neuer Therapien zur Verhinderung thromboembolischer Ereignisse, die auf Thrombin-vermittelte Signalwege abzielen. Dazu gehören Nicht-Vitamin-K-Antagonist-orale Antikoagulantien (NOAKs). Dieser Artikel soll die aktuellen klinischen Studien zusammenfassen, in denen die Rolle von NOACs bei koronarer Herzerkrankung untersucht wurde.

Keywords

coronary artery disease - non–vitamin K antagonist - oral anticoagulants - direct antithrombin agents - atherosclerosis

Schlüsselwörter

koronare Herzkrankheit - Nicht-Vitamin-K-Antagonist - orale Antikoagulantien (NOAKs) - direkte Antithrombinmittel - Arteriosklerose


Publication History

Received: 10 November 2020

Accepted: 23 August 2021

Article published online:
18 October 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Finegold JA, Asaria P, Francis DP. Mortality from ischaemic heart disease by country, region, and age: statistics from World Health Organisation and United Nations. Int J Cardiol 2013; 168 (02) 934-945
    CrossrefPubMedSearch in Google Scholar
  • 2 Ibanez B, James S, Agewall S. et al; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018; 39 (02) 119-177
    CrossrefPubMedSearch in Google Scholar
  • 3 Knuuti J, Wijns W, Saraste A. et al; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J 2020; 41 (03) 407-477
    CrossrefPubMedSearch in Google Scholar
  • 4 Roffi M, Patrono C, Collet J-P. et al; ESC Scientific Document Group. 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 2016; 37 (03) 267-315
    CrossrefPubMedSearch in Google Scholar
  • 5 Merlini PA, Bauer KA, Oltrona L. et al. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation 1994; 90 (01) 61-68
    CrossrefPubMedSearch in Google Scholar
  • 6 van Es RF, Jonker JJC, Verheugt FWA, Deckers JW, Grobbee DE. 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 (9327): 109-113
    CrossrefPubMedSearch in Google Scholar
  • 7 Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002; 347 (13) 969-974
    CrossrefPubMedSearch in Google Scholar
  • 8 Al Said S, Bode C, Duerschmied D. Anticoagulation in atherosclerotic disease. Hamostaseologie 2018; 38 (04) 240-246
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Mekaj YH, Mekaj AY, Duci SB, Miftari EI. New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events. Ther Clin Risk Manag 2015; 11: 967-977
    CrossrefPubMedSearch in Google Scholar
  • 10 Ruff CT, Giugliano RP, Braunwald E. et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383 (9921): 955-962
    Search in Google Scholar
  • 11 Hindricks G, Potpara T, Dagres N. et al; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42 (05) 373-498 [Erratum in: Eur Heart J. 2021 Feb 1;42(5):507, 546–547, 541–543]
    Search in Google Scholar
  • 12 Sang Y, Roest M, de Laat B, de Groot PG, Huskens D. Interplay between platelets and coagulation. Blood Rev 2021; 46: 100733
    CrossrefPubMedSearch in Google Scholar
  • 13 Brass LF. Thrombin and platelet activation. Chest 2003; 124 (03) , Suppl): 18S-25S
    CrossrefPubMedSearch in Google Scholar
  • 14 Steppich B, Dobler F, Brendel LC. et al. Effect of the FXa inhibitors rivaroxaban and apixaban on platelet activation in patients with atrial fibrillation. J Thromb Thrombolysis 2017; 43 (04) 490-497
    CrossrefPubMedSearch in Google Scholar
  • 15 Sokol J, Nehaj F, Ivankova J. et al. Impact of edoxaban on thrombin-dependent platelet aggregation. Clin Appl Thromb Hemost 2020; 26: 1076029620948585
    CrossrefPubMedSearch in Google Scholar
  • 16 Honda Y, Kamisato C, Morishima Y. Edoxaban, a direct factor Xa inhibitor, suppresses tissue-factor induced human platelet aggregation and clot-bound factor Xa in vitro: comparison with an antithrombin-dependent factor Xa inhibitor, fondaparinux. Thromb Res 2016; 141: 17-21
    CrossrefPubMedSearch in Google Scholar
  • 17 Nehaj F, Sokol J, Ivankova J, Mokan M, Mokan M, Stasko J. Edoxaban affects TRAP-dependent platelet aggregation. J Thromb Thrombolysis 2020; 49 (04) 578-583
    CrossrefPubMedSearch in Google Scholar
  • 18 Sokol J, Nehaj F, Ivankova J, Mokan M, Mokan M, Stasko J. Dabigatran affects thrombin-dependent platelet aggregation after a week-long therapy. Scand Cardiovasc J 2018; 52 (04) 227-231
    CrossrefPubMedSearch in Google Scholar
  • 19 Shimizu M, Natori T, Tsuda K. et al. Thrombin-induced platelet aggregation -effect of dabigatran using automated platelet aggregometry. Platelets 2020; 31 (03) 360-364
    CrossrefPubMedSearch in Google Scholar
  • 20 Vinholt PJ, Nielsen C, Söderström AC, Brandes A, Nybo M. Dabigatran reduces thrombin-induced platelet aggregation and activation in a dose-dependent manner. J Thromb Thrombolysis 2017; 44 (02) 216-222
    CrossrefPubMedSearch in Google Scholar
  • 21 Olivier CB, Weik P, Meyer M. et al. TRAP-induced platelet aggregation is enhanced in cardiovascular patients receiving dabigatran. Thromb Res 2016; 138: 63-68
    CrossrefPubMedSearch in Google Scholar
  • 22 Olivier CB, Weik P, Meyer M. et al. Dabigatran and rivaroxaban do not affect AA- and ADP-induced platelet aggregation in patients receiving concomitant platelet inhibitors. J Thromb Thrombolysis 2016; 42 (02) 161-166
    CrossrefPubMedSearch in Google Scholar
  • 23 Eikelboom JW, Connolly SJ, Bosch J. et al; COMPASS Investigators. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017; 377 (14) 1319-1330
    Search in Google Scholar
  • 24 Bhatt DL, Fox KAA, Hacke W. et al; CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006; 354 (16) 1706-1717
    CrossrefPubMedSearch in Google Scholar
  • 25 Sorbets E, Steg PG. Direct-acting anticoagulants in chronic coronary syndromes. Eur Cardiol 2020; 15: 1-7
    CrossrefPubMedSearch in Google Scholar
  • 26 De Caterina R, Husted S, Wallentin L. et al. Oral anticoagulants in coronary heart disease (Section IV). Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease. Thromb Haemost 2016; 115 (04) 685-711
    Thieme ConnectPubMedSearch in Google Scholar
  • 27 Bosch J, Eikelboom JW, Connolly SJ. et al. Rationale, design and baseline characteristics of participants in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) Trial. Can J Cardiol 2017; 33 (08) 1027-1035
    CrossrefPubMedSearch in Google Scholar
  • 28 Moayyedi P, Eikelboom JW, Bosch J. et al; COMPASS Investigators. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology 2019; 157 (03) 682-691.e2
    CrossrefPubMedSearch in Google Scholar
  • 29 Alsaid S, Bode C, Duerschmied D. Perspektive nach der COMPASS-Studie für KHK- und AVK-Patienten: Die neue Rolle der oralen Antikoagulationstherapie bei atherosklerotischer Erkrankung. Der Klinikarzt 2019; 48 (03) 73-77
    Thieme ConnectPubMedSearch in Google Scholar
  • 30 Steffel J, Eikelboom JW, Anand SS, Shestakovska O, Yusuf S, Fox KAA. The COMPASS trial: net clinical benefit of low-dose rivaroxaban plus aspirin as compared with aspirin in patients with chronic vascular disease. Circulation 2020; 142 (01) 40-48 [Erratum in: Circulation. 2020 Jul 7;142(1):e23. PMID: 32436455]
    CrossrefPubMedSearch in Google Scholar
  • 31 Oldgren J, Budaj A, Granger CB. et al; RE-DEEM Investigators. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J 2011; 32 (22) 2781-2789
    CrossrefPubMedSearch in Google Scholar
  • 32 Alexander JH, Lopes RD, James S. et al; APPRAISE-2 Investigators. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011; 365 (08) 699-708
    CrossrefPubMedSearch in Google Scholar
  • 33 Gibson CM, Mega JL, Burton P. et al. Rationale and design of the anti-Xa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome-thrombolysis in myocardial infarction 51 (ATLAS-ACS 2 TIMI 51) trial: a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of rivaroxaban in subjects with acute coronary syndrome. Am Heart J 2011; 161 (05) 815-821.e6
    CrossrefPubMedSearch in Google Scholar
  • 34 Mega JL, Braunwald E, Wiviott SD. et al; ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012; 366 (01) 9-19
    CrossrefPubMedSearch in Google Scholar
  • 35 Mega JL, Braunwald E, Wiviott SD. et al. Comparison of the efficacy and safety of two rivaroxaban doses in acute coronary syndrome (from ATLAS ACS 2-TIMI 51). Am J Cardiol 2013; 112 (04) 472-478
    CrossrefPubMedSearch in Google Scholar
  • 36 Khera S, Kolte D, Bhatt DL. Percutaneous Coronary Intervention [Internet]. Translational Research in Coronary Artery Disease; 2016: 179-194
    CrossrefSearch in Google Scholar
  • 37 Al Said S, Katus HA, Alabed S. Cochrane corner: NOACs in atrial fibrillation patients post-percutaneous coronary intervention. Heart 2020; 106 (17) 1293-1295
    CrossrefPubMedSearch in Google Scholar
  • 38 Valgimigli M, Bueno H, Byrne RA. et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. [in Polish]. Kardiol Pol 2017; 75 (12) 1217-1299
    CrossrefPubMedSearch in Google Scholar
  • 39 Dewilde WJM, Oirbans T, Verheugt FWA. 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 (9872): 1107-1115
    CrossrefPubMedSearch in Google Scholar
  • 40 Fiedler KA, 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 (16) 1619-1629
    CrossrefPubMedSearch in Google Scholar
  • 41 Gibson CM, Mehran R, Bode C. et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med 2016; 375 (25) 2423-2434
    CrossrefPubMedSearch in Google Scholar
  • 42 Cannon CP, Bhatt DL, Oldgren J. et al; RE-DUAL PCI Steering Committee and Investigators. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med 2017; 377 (16) 1513-1524
    CrossrefPubMedSearch in Google Scholar
  • 43 Lopes RD, Heizer G, Aronson R. et al; AUGUSTUS Investigators. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med 2019; 380 (16) 1509-1524
    CrossrefPubMedSearch in Google Scholar
  • 44 Vranckx P, Valgimigli M, Eckardt L. et al. 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; 394 (10206): 1335-1343
    CrossrefPubMedSearch in Google Scholar
  • 45 Lopes RD, Hong H, Harskamp RE. et al. Optimal antithrombotic regimens for patients with atrial fibrillation undergoing percutaneous coronary intervention: an updated network meta-analysis. JAMA Cardiol 2020; 5 (05) 582-589
    CrossrefPubMedSearch in Google Scholar
  • 46 Al Said S, Alabed S, Kaier K. et al. Non-vitamin K antagonist oral anticoagulants (NOACs) post-percutaneous coronary intervention: a network meta-analysis. Cochrane Database Syst Rev 2019; 12: CD013252
    PubMedSearch in Google Scholar
  • 47 Gargiulo G, Goette A, Tijssen J. et al. 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; 40 (46) 3757-3767
    CrossrefPubMedSearch in Google Scholar
  • 48 Galli M, Andreotti F, Porto I, Crea F. Intracranial haemorrhages vs. stent thromboses with direct oral anticoagulant plus single antiplatelet agent or triple antithrombotic therapy: a meta-analysis of randomized trials in atrial fibrillation and percutaneous coronary intervention/acute coronary syndrome patients. Europace 2020; 22 (04) 538-546
    CrossrefPubMedSearch in Google Scholar
  • 49 Sullivan AE, Nanna MG, Rao SV. et al. A systematic review of randomized trials comparing double versus triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv 2020; 96 (02) E102-E109
    CrossrefPubMedSearch in Google Scholar
  • 50 Moon JY, Franchi F, Rollini F, Angiolillo DJ. Evolution of coronary stent technology and implications for duration of dual antiplatelet therapy. Prog Cardiovasc Dis 2018; 60 (4-5): 478-490
    CrossrefPubMedSearch in Google Scholar
  • 51 Lopes RD, Leonardi S, Wojdyla DM. et al. Stent thrombosis in patients with atrial fibrillation undergoing coronary stenting in the AUGUSTUS trial. Circulation 2020; 141 (09) 781-783
    CrossrefPubMedSearch in Google Scholar
  • 52 Casula M, Fortuni F, Ferlini M, Fabris F, Oltrona Visconti L, Leonardi S. Meta-analysis comparing potent oral P2Y12 inhibitors versus clopidogrel in patients with atrial fibrillation undergoing percutaneous coronary intervention. Am J Cardiovasc Drugs 2021; 21 (02) 231-240
    CrossrefPubMedSearch in Google Scholar
  • 53 Angiolillo DJ, Bhatt DL, Cannon CP. et al. Antithrombotic therapy in patients with atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary intervention: a North American perspective: 2021 update. Circulation 2021; 143 (06) 583-596
    CrossrefPubMedSearch in Google Scholar
  • 54 Lip GYH, Collet JP, Haude M. et al; ESC Scientific Document Group. 2018 Joint European consensus document on the management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous cardiovascular interventions: a joint consensus document of the European Heart Rhythm Association (EHRA), European Society of Cardiology Working Group on Thrombosis, European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA). Europace 2019; 21 (02) 192-193
    CrossrefPubMedSearch in Google Scholar
  • 55 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: 129-132
    CrossrefPubMedSearch in Google Scholar
  • 56 U.S. National Library of Medicine. Apixaban vs. phenprocoumon in patients with ACS and AF: APPROACH-ACS-AF (approach). , 2016. Available at: https://clinicaltrials.gov/ct2/show/NCT02789917. [Last update posted: August 14, 2020]
    PubMed
  • 57 Dabigatran versus warfarin with NVAF who undergo PCI. 2018 . Available: clinicaltrials.gov/ct2/show/ NCT03536611 [Last update posted: January 4, 2019]
    PubMedSearch in Google Scholar