open access

Ahead of print
Invited Review
Published online: 2021-06-02
Get Citation

A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study

Jacek Kubica, Piotr Adamski, Piotr Niezgoda, Aldona Kubica, Przemysław Podhajski, Malwina Barańska, Julia M. Umińska, Łukasz Pietrzykowski, Małgorzata Ostrowska, Jolanta M. Siller-Matula, Jolita Badarienė, Stanisław Bartuś, Andrzej Budaj, Sławomir Dobrzycki, Łukasz Fidor, Mariusz Gąsior, Jacek Gessek, Marek Gierlotka, Robert Gil, Jarosław Gorący, Paweł Grzelakowski, Tomasz Hajdukiewicz, Miłosz Jaguszewski, Marianna Janion, Jarosław Kasprzak, Adam Kern, Artur Klecha, Andrzej Kleinrok, Wacław Kochman, Bartosz Krakowiak, Jacek Legutko, Maciej Lesiak, Marcin Nosal, Grzegorz Piotrowski, Andrzej Przybylski, Tomasz Roleder, Grzegorz Skonieczny, Grzegorz Sobieszek, Agnieszka Tycińska, Dariusz Wojciechowski, Wojciech Wojakowski, Jarosław Wójcik, Marzenna Zielińska, Aleksander Żurakowski, Giuseppe Specchia, Diana A. Gorog, Eliano P. Navarese
DOI: 10.5603/CJ.a2021.0056
·
Pubmed: 34096012

open access

Ahead of print
Invited Review
Published online: 2021-06-02

Abstract

The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far.
We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome — a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients.
The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up (ClinicalTrials.gov Identifier: NCT04718025; EudraCT number: 2020-005130-15).

Abstract

The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far.
We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome — a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients.
The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up (ClinicalTrials.gov Identifier: NCT04718025; EudraCT number: 2020-005130-15).

Get Citation

Keywords

acute coronary syndrome, ticagrelor, antiplatelet therapy, de-escalation, ELECTRA-SIRIO 2

About this article
Title

A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study

Journal

Cardiology Journal

Issue

Ahead of print

Article type

Invited Review

Published online

2021-06-02

DOI

10.5603/CJ.a2021.0056

Pubmed

34096012

Keywords

acute coronary syndrome
ticagrelor
antiplatelet therapy
de-escalation
ELECTRA-SIRIO 2

Authors

Jacek Kubica
Piotr Adamski
Piotr Niezgoda
Aldona Kubica
Przemysław Podhajski
Malwina Barańska
Julia M. Umińska
Łukasz Pietrzykowski
Małgorzata Ostrowska
Jolanta M. Siller-Matula
Jolita Badarienė
Stanisław Bartuś
Andrzej Budaj
Sławomir Dobrzycki
Łukasz Fidor
Mariusz Gąsior
Jacek Gessek
Marek Gierlotka
Robert Gil
Jarosław Gorący
Paweł Grzelakowski
Tomasz Hajdukiewicz
Miłosz Jaguszewski
Marianna Janion
Jarosław Kasprzak
Adam Kern
Artur Klecha
Andrzej Kleinrok
Wacław Kochman
Bartosz Krakowiak
Jacek Legutko
Maciej Lesiak
Marcin Nosal
Grzegorz Piotrowski
Andrzej Przybylski
Tomasz Roleder
Grzegorz Skonieczny
Grzegorz Sobieszek
Agnieszka Tycińska
Dariusz Wojciechowski
Wojciech Wojakowski
Jarosław Wójcik
Marzenna Zielińska
Aleksander Żurakowski
Giuseppe Specchia
Diana A. Gorog
Eliano P. Navarese

References (48)
  1. Valgimigli M, Bueno H, Byrne RA, et al. ESC Scientific Document Group, ESC Committee for Practice Guidelines (CPG), ESC National Cardiac Societies. 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): 213–260.
  2. 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.
  3. Adamski P, Adamska U, Ostrowska M, et al. New directions for pharmacotherapy in the treatment of acute coronary syndrome. Expert Opin Pharmacother. 2016; 17(17): 2291–2306.
  4. 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. 2021; 42(14): 1289–1367.
  5. Kubica J, Adamski P, Niezgoda P, et al. Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines. Cardiol J. 2020; 27(6): 661–676.
  6. 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.
  7. Claassens DMf, Sibbing D. De-Escalation of antiplatelet treatment in patients with myocardial infarction who underwent percutaneous coronary intervention: a review of the current literature. J Clin Med. 2020; 9(9).
  8. 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.
  9. Cuisset T, Deharo P, Quilici J, et al. Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study. Eur Heart J. 2017; 38(41): 3070–3078.
  10. De Luca L, D'Ascenzo F, Musumeci G, et al. Incidence and outcome of switching of oral platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: the SCOPE registry. EuroIntervention. 2017; 13(4): 459–466.
  11. Sibbing D, Aradi D, Jacobshagen C, et al. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 2017; 390(10104): 1747–1757.
  12. 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.
  13. Kheiri B, Osman M, Abdalla A, et al. De-Escalation of antiplatelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis of randomized clinical trials. J Cardiovasc Pharmacol Ther. 2019; 24(2): 153–159.
  14. Kubica J, Adamski P, Ostrowska M, et al. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J. 2016; 37(3): 245–252.
  15. Hobl EL, Reiter B, Schoergenhofer C, et al. Morphine decreases ticagrelor concentrations but not its antiplatelet effects: a randomized trial in healthy volunteers. Eur J Clin Invest. 2016; 46(1): 7–14.
  16. Kubica J, Kubica A, Jilma B, et al. Impact of morphine on antiplatelet effects of oral P2Y12 receptor inhibitors. Int J Cardiol. 2016; 215: 201–208.
  17. Adamski P, Ostrowska M, Navarese EP, et al. Pharmacodynamic and clinical efficacy of reduced ticagrelor maintenance doses in patients with coronary artery disease. Curr Med Res Opin. 2021; 37(2): 195–206.
  18. 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.
  19. Ostrowska M, Kubica J, Adamski P, et al. Stratified approaches to antiplatelet therapies based on platelet reactivity testing. Front Cardiovasc Med. 2019; 6: 176.
  20. Adamski P, Sikora J, Laskowska E, et al. Comparison of bioavailability and antiplatelet action of ticagrelor in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction: A prospective, observational, single-centre study. PLoS One. 2017; 12(10): e0186013.
  21. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 361(11): 1045–1057.
  22. Wiviott S, Braunwald E, McCabe C, et al. TRITON-TIMI 38 Investigators. Prasugrel versus copidogrel in patients with acute coronary syndromes. N Engl J Med. 2007; 357(20): 2001–2015.
  23. 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.
  24. Storey RF, Angiolillo DJ, Bonaca MP, et al. Platelet inhibition with ticagrelor 60 mg versus 90 mg twice daily in the PEGASUS-TIMI 54 trial. J Am Coll Cardiol. 2016; 67(10): 1145–1154.
  25. Bonaca MP, Bhatt DL, Oude Ophuis T, et al. Long-term tolerability of ticagrelor for the secondary prevention of major adverse cardiovascular events: a secondary analysis of the PEGASUS-TIMI 54 trial. JAMA Cardiol. 2016; 1(4): 425–432.
  26. 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.
  27. 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.
  28. Mehran R, Baber U, Sharma S, et al. Ticagrelor with or without Aspirin in High-Risk Patients after PCI. N Engl J Med. 2019; 381(21): 2032–2042.
  29. Dangas G, Baber U, Sharma S, et al. Ticagrelor with or without aspirin after complex PCI: the TWILIGHT-COMPLEX analysis. J Am Coll Cardiol. 2020; 75(19): 2414–2424.
  30. Gelbenegger G, Schoergenhofer C, Jilma B, et al. Efficacy and safety of ticagrelor monotherapy in patients undergoing percutaneous coronary intervention: a meta-analysis. Clin Pharmacol Ther. 2021 [Epub ahead of print].
  31. Khan SU, Khan MZ, Khan MS, et al. De-escalation of antiplatelets after percutaneous coronary intervention: a bayesian network meta-analysis of various de-escalation strategies. Eur Heart J Cardiovasc Pharmacother. 2020 [Epub ahead of print].
  32. Pietrzykowski Ł, Kasprzak M, Michalski P, et al. Therapy discontinuation after myocardial infarction. J Clin Med. 2020; 9(12): 4109.
  33. Kołodziejczak M, Navarese E, Kubica J. Rationale and design of PREvalence of DyspneA in patients treated with TicagrelOR (PREDATOR) program. Med Res J. 2018.
  34. 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.
  35. 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.
  36. Kubica A. Self-reported questionnaires for a comprehensive assessment of patients after acute coronary syndrome. Med Res J. 2019; 4(2): 106–109.
  37. 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].
  38. Kubica A, Kosobucka A, Fabiszak T, et al. Assessment of adherence to medication in patients after myocardial infarction treated with percutaneous coronary intervention. Is there a place for newself-reported questionnaires? Curr Med Res Opin. 2019; 35(2): 341–349.
  39. Kosobucka A, Michalski P, Pietrzykowski Ł, et al. Adherence to treatment assessed with the Adherence in Chronic Diseases Scale in patients after myocardial infarction. Patient Prefer Adherence. 2018; 12: 333–340.
  40. Pietrzykowski Ł, Michalski P, Kosobucka A, et al. Medication adherence and its determinants in patients after myocardial infarction. Sci Rep. 2020; 10(1): 12028.
  41. Kosobucka A, Pietrzykowski Ł, Michalski P, et al. Impact of readiness for discharge from the hospital on the implementation of the therapeutic plan. Med Res J. 2020; 5(4): 256–264.
  42. Michalski P, Kasprzak M, Siedlaczek M, et al. The impact of knowledge and effectiveness of educational intervention on readiness for hospital discharge and adherence to therapeutic recommendations in patients with acute coronary syndrome. Med Res J. 2020.
  43. Kubica A, Kosobucka A, Michalski P, et al. Self-reported questionnaires for assessment adherence to treatment in patients with cardiovascular diseases. Med Res J. 2018; 2(4): 115–122.
  44. Kubica A, Gruchała M, Jaguszewski M, et al. Adherence to treatment — a pivotal issue in long-term treatment of patients with cardiovascular diseases. An expert standpoint. Med Res J. 2018; 2(4): 123–127.
  45. Buszko K, Pietrzykowski Ł, Michalski P, et al. Validation of the Functioning in Chronic Illness Scale (FCIS). Med Res J. 2018; 3(2): 63–69.
  46. Pietrzykowski Ł, Michalski P, Kosobucka A, et al. Knowledge about health and disease in obese patients after myocardial infarction. An observational study. Med Res J. 2018; 2(4): 135–140.
  47. Buszko K, Kosobucka A, Michalski P, et al. The readiness for hospital discharge of patients after acute myocardial infarction: a new self-reported questionnaire. Med Res J. 2017; 2(1): 20–28.
  48. Kubica A, Adamski P, Bączkowska A, et al. The rationale for Multilevel Educational and Motivational Intervention in Patients after Myocardial Infarction (MEDMOTION) project is to support multicentre randomized clinical trial Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome (ELECTRA-SIRIO 2). Med Res J. 2020; 5(4): 244–249.

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