open access

Ahead of print
Experts' viewpoint
Published online: 2020-10-14
Get Citation

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines

Jacek Kubica, Piotr Adamski, Piotr Niezgoda, Dimitrios Alexopoulos, Jolita Badarienė, Andrzej Budaj, Katarzyna Buszko, Dariusz Dudek, Tomasz Fabiszak, Mariusz Gąsior, Robert Gil, Diana A. Gorog, Stefan Grajek, Paul A. Gurbel, Marcin Gruchała, Miłosz J. Jaguszewski, Stefan James, Young-Hoon Jeong, Bernd Jilma, Jarosław D. Kasprzak, Andrzej Kleinrok, Aldona Kubica, Wiktor Kuliczkowski, Jacek Legutko, Maciej Lesiak, Jolanta M. Siller-Matula, Klaudiusz Nadolny, Krzysztof Pstrągowski, Salvatore Di Somma, Giuseppe Specchia, Janina Stępińska, Udaya Tantry, Agnieszka Tycińska, Monica Verdoia, Wojciech Wojakowski, Eliano P. Navarese
DOI: 10.5603/CJ.a2020.0132
·
Pubmed: 33073857

open access

Ahead of print
Experts' viewpoint
Published online: 2020-10-14

Abstract

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the dual antiplatelet therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor.

The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group.

Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic treatment (DATT) appear after a longer time from ACS (more than two years) and/or from cessation of DAPT (more than one year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials.

Abstract

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the dual antiplatelet therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor.

The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group.

Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic treatment (DATT) appear after a longer time from ACS (more than two years) and/or from cessation of DAPT (more than one year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials.

Get Citation

Keywords

prolonged antithrombotic therapy, chronic coronary syndrome, acute coronary syndrome, rivaroxaban, ticagrelor, clopidogrel, prasugrel

About this article
Title

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines

Journal

Cardiology Journal

Issue

Ahead of print

Published online

2020-10-14

DOI

10.5603/CJ.a2020.0132

Pubmed

33073857

Keywords

prolonged antithrombotic therapy
chronic coronary syndrome
acute coronary syndrome
rivaroxaban
ticagrelor
clopidogrel
prasugrel

Authors

Jacek Kubica
Piotr Adamski
Piotr Niezgoda
Dimitrios Alexopoulos
Jolita Badarienė
Andrzej Budaj
Katarzyna Buszko
Dariusz Dudek
Tomasz Fabiszak
Mariusz Gąsior
Robert Gil
Diana A. Gorog
Stefan Grajek
Paul A. Gurbel
Marcin Gruchała
Miłosz J. Jaguszewski
Stefan James
Young-Hoon Jeong
Bernd Jilma
Jarosław D. Kasprzak
Andrzej Kleinrok
Aldona Kubica
Wiktor Kuliczkowski
Jacek Legutko
Maciej Lesiak
Jolanta M. Siller-Matula
Klaudiusz Nadolny
Krzysztof Pstrągowski
Salvatore Di Somma
Giuseppe Specchia
Janina Stępińska
Udaya Tantry
Agnieszka Tycińska
Monica Verdoia
Wojciech Wojakowski
Eliano P. Navarese

References (55)
  1. Neumann FJ, Sousa-Uva M, Ahlsson A, et al. ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019; 40(2): 87–165.
  2. Myat A, Tantry US, Kubica J, et al. Current controversies in the use of aspirin and ticagrelor for the treatment of thrombotic events. Expert Rev Cardiovasc Ther. 2016; 14(12): 1361–1370.
  3. Navarese EP, Khan SU, Kołodziejczak M, et al. Comparative Efficacy and Safety of Oral P2Y Inhibitors in Acute Coronary Syndrome: Network Meta-Analysis of 52 816 Patients From 12 Randomized Trials. Circulation. 2020; 142(2): 150–160.
  4. Kubica J, Adamski P, Paciorek P, et al. Treatment of patients with acute coronary syndrome: Recommendations for medical emergency teams: Focus on antiplatelet therapies. Updated experts' standpoint. Cardiol J. 2018; 25(3): 291–300.
  5. Kubica J, Jaguszewski M. ISAR-REACT 5 - What have we learned? Cardiol J. 2019; 26(5): 427–428.
  6. Ostrowska M, Kubica J, Adamski P, et al. Stratified Approaches to Antiplatelet Therapies Based on Platelet Reactivity Testing. Front Cardiovasc Med. 2019; 6: 176.
  7. Fox KAA, Carruthers KF, Dunbar DR, et al. Underestimated and under-recognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian Study). Eur Heart J. 2010; 31(22): 2755–2764.
  8. Jernberg T, Hasvold P, Henriksson M, et al. Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J. 2015; 36(19): 1163–1170.
  9. Rapsomaniki E, Thuresson M, Yang E, et al. Using big data from health records from four countries to evaluate chronic disease outcomes: a study in 114 364 survivors of myocardial infarction. Eur Heart J Qual Care Clin Outcomes. 2016; 2(3): 172–183.
  10. 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(3): 407–477.
  11. Collet JP, Thiele H, Barbato E, et al. ESC Scientific Document Group . 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2020 [Epub ahead of print].
  12. Kubica J, Adamski P, Buszko K, et al. Platelet inhibition with standard vs. lower maintenance dose of ticagrelor early after myocardial infarction (ELECTRA): a randomized, open-label, active-controlled pharmacodynamic and pharmacokinetic study. Eur Heart J Cardiovasc Pharmacother. 2019; 5(3): 139–148.
  13. Kubica J, Adamski P, Buszko K, et al. Rationale and Design of the Effectiveness of LowEr maintenanCe dose of TicagRelor early After myocardial infarction (ELECTRA) pilot study. Eur Heart J Cardiovasc Pharmacother. 2018; 4(3): 152–157.
  14. Mauri L, Kereiakes DJ, Yeh RW, et al. DAPT Study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014; 371(23): 2155–2166.
  15. Yeh RW, Kereiakes DJ, Steg PG, et al. DAPT Study Investigators. Benefits and Risks of Extended Duration Dual Antiplatelet Therapy After PCI in Patients With and Without Acute Myocardial Infarction. J Am Coll Cardiol. 2015; 65(20): 2211–2221.
  16. Garratt KN, Weaver WD, Jenkins RG, et al. Prasugrel plus aspirin beyond 12 months is associated with improved outcomes after TAXUS Liberté paclitaxel-eluting coronary stent placement. Circulation. 2015; 131(1): 62–73.
  17. Bonaca MP, Bhatt DL, Cohen M, et al. PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015; 372(19): 1791–1800.
  18. Bhatt DL, Bonaca MP, Bansilal S, et al. Reduction in Ischemic Events With Ticagrelor in Diabetic Patients With Prior Myocardial Infarction in PEGASUS-TIMI 54. J Am Coll Cardiol. 2016; 67(23): 2732–2740.
  19. Bonaca MP, Bhatt DL, Storey RF, et al. Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease. J Am Coll Cardiol. 2016; 67(23): 2719–2728.
  20. Bonaca MP, Bhatt DL, Steg PG, et al. Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54. Eur Heart J. 2016; 37(14): 1133–1142.
  21. Bansilal S, Bonaca MP, Cornel JH, et al. Ticagrelor for Secondary Prevention of Atherothrombotic Events in Patients With Multivessel Coronary Disease. J Am Coll Cardiol. 2018; 71(5): 489–496.
  22. Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017; 377(14): 1319–1330.
  23. Adamski P, Adamska U, Ostrowska M, et al. Evaluating current and emerging antithrombotic therapy currently available for the treatment of acute coronary syndrome in geriatric populations. Expert Opin Pharmacother. 2018; 19(13): 1415–1425.
  24. Boinska J, Koziński M, Kasprzak M, et al. Diurnal variations in tissue factor and tissue factor pathway inhibitor concentrations in relation to on-treatment platelet reactivity: an analysis of patients with acute myocardial infarction. Platelets. 2020; 31(7): 877–883.
  25. Adamski P, Buszko K, Sikora J, et al. Determinants of high platelet reactivity in patients with acute coronary syndromes treated with ticagrelor. Sci Rep. 2019; 9(1): 3924.
  26. Mauri L, Kereiakes DJ, Normand SLT, et al. Rationale and design of the dual antiplatelet therapy study, a prospective, multicenter, randomized, double-blind trial to assess the effectiveness and safety of 12 versus 30 months of dual antiplatelet therapy in subjects undergoing percutaneous coronary intervention with either drug-eluting stent or bare metal stent placement for the treatment of coronary artery lesions. Am Heart J. 2010; 160(6): 1035–41, 1041.e1.
  27. Li P, Liu JP. Long-term risk of late and very late stent thrombosis in patients treated with everolimus against paclitaxel-eluting stents: an updated meta-analysis. Coron Artery Dis. 2014; 25(5): 369–377.
  28. Dangas GD, Serruys PW, Kereiakes DJ, et al. Meta-analysis of everolimus-eluting versus paclitaxel-eluting stents in coronary artery disease: final 3-year results of the SPIRIT clinical trials program (Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions). JACC Cardiovasc Interv. 2013; 6(9): 914–922.
  29. EMA/CHMP/18297/2016. 17 December 2015. http://www.ema.europa.eu/docs/ en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/ 001241/WC500203874.pdf (17 June 2019).
  30. Dellborg M, Bonaca MP, Storey RF, et al. Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54. Eur Heart J Cardiovasc Pharmacother. 2019; 5(4): 200–206.
  31. Verdoia M, Kedhi E, Suryapranata H, et al. Ticagrelor in the prevention of coronary and non-coronary atherothrombotic events: A comprehensive meta-analysis of 10 randomized trials. Atherosclerosis. 2019; 284: 136–147.
  32. Furtado RHM, Nicolau JC, Magnani G, et al. Long-term ticagrelor for secondary prevention in patients with prior myocardial infarction and no history of coronary stenting: insights from PEGASUS-TIMI 54. Eur Heart J. 2020; 41(17): 1625–1632.
  33. Gurbel PA, Fox KAA, Tantry US, et al. Combination antiplatelet and oral anticoagulant therapy in patients with coronary and peripheral artery disease. Circulation. 2019; 139(18): 2170–2185.
  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(1): 9–19.
  35. Connolly S, Eikelboom J, Bosch J, et al. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018; 391(10117): 205–218.
  36. Bhatt DL, Eikelboom JW, Connolly SJ, et al. COMPASS Steering Committee and Investigators. Role of Combination Antiplatelet and Anticoagulation Therapy in Diabetes Mellitus and Cardiovascular Disease: Insights From the COMPASS Trial. Circulation. 2020; 141(23): 1841–1854.
  37. Steffel J, Eikelboom JW, Anand SS, et al. 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(1): 40–48.
  38. Sharma M, Hart RG, Connolly SJ, et al. Stroke Outcomes in the COMPASS Trial. Circulation. 2019; 139(9): 1134–1145.
  39. Bainey KR, Welsh RC, Connolly SJ, et al. COMPASS Investigators. Rivaroxaban plus aspirin versus aspirin alone in patients with prior percutaneous coronary intervention (COMPASS-PCI). Circulation. 2020; 141(14): 1141–1151.
  40. Kozinski M, Bielis L, Wisniewska-Szmyt J, et al. Diurnal variation in platelet inhibition by clopidogrel. Platelets. 2011; 22(8): 579–587.
  41. Kubica A, Kozinski M, Grzesk G, et al. Genetic determinants of platelet response to clopidogrel. J Thromb Thrombolysis. 2011; 32(4): 459–466.
  42. Kubica A, Kasprzak M, Siller-Matula J, et al. Time-related changes in determinants of antiplatelet effect of clopidogrel in patients after myocardial infarction. Eur J Pharmacol. 2014; 742: 47–54.
  43. Gurbel PA, Tantry US. Do platelet function testing and genotyping improve outcome in patients treated with antithrombotic agents?: platelet function testing and genotyping improve outcome in patients treated with antithrombotic agents. Circulation. 2012; 125(10): 1276–1287; discussion 1287.
  44. Brunetti ND, De Gennaro L, Di Biase M, et al. Prolonged double antiplatelet therapy vs association of antiplatelet and low dose of anticoagulant therapy: PEGASUS or COMPASS? Int J Cardiol Heart Vasc. 2019; 24: 100401.
  45. Capodanno D, Bhatt DL, Eikelboom JW, et al. Dual-pathway inhibition for secondary and tertiary antithrombotic prevention in cardiovascular disease. Nat Rev Cardiol. 2020; 17(4): 242–257.
  46. Ramacciotti E, Weitz JI. Rivaroxaban plus aspirin for cardiovascular protection: Rationale for the vascular dose and dual pathway inhibition. Thromb Res. 2019; 184: 44–49.
  47. González-Juanatey JR, Almendro-Delia M, Cosín-Sales J, et al. Residual risk reduction opportunities in patients with chronic coronary syndrome. Role of dual pathway inhibition. Expert Rev Clin Pharmacol. 2020; 13(7): 695–706.
  48. Kalbacher D, Waldeyer C, Blankenberg S, et al. Beyond conventional secondary prevention in coronary artery disease-what to choose in the era of CANTOS, COMPASS, FOURIER, ODYSSEY and PEGASUS-TIMI 54? A review on contemporary literature. Ann Transl Med. 2018; 6(16): 323.
  49. Kubica A, Kasprzak M, Obońska K, et al. Discrepancies in assessment of adherence to antiplatelet treatment after myocardial infarction. Pharmacology. 2015; 95(1-2): 50–58.
  50. Kubica A, Obońska K, Kasprzak M, et al. Prediction of high risk of non-adherence to antiplatelet treatment. Kardiol Pol. 2016; 74(1): 61–67.
  51. Kubica A, Obońska K, Fabiszak T, et al. Adherence to antiplatelet treatment with P2Y12 receptor inhibitors. Is there anything we can do to improve it? A systematic review of randomized trials. Curr Med Res Opin. 2016; 32(8): 1441–1451.
  52. Kosobucka A, Michalski P, Pietrzykowski Ł, et al. The impact of readiness to discharge from hospital on adherence to treatment in patients after myocardial infarction. Cardiol J. 2020 [Epub ahead of print].
  53. Pietrzykowski Ł, Michalski P, Kosobucka A, et al. Medication adherence and its determinants in patients after myocardial infarction. Sci Rep. 2020; 10(1): 12028.
  54. Kubica A, Bączkowska A. Uzasadnienie interwencji motywacyjnych jako kluczowego elementu projektu wielopoziomowej edukacji i motywacji u pacjentów z zawałem serca (MEDMOTION). Folia Cardiologica. 2020; 15(1): 6–10.
  55. Gurbel PA, Tantry US. Deciding about prolonged ticagrelor therapy in coronary clot formers: an ongoing dilemma. Eur Heart J. 2016; 37(14): 1143–1144.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl