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

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).

Keywords: ELECTRA-SIRIO 2; acute coronary syndrome; antiplatelet therapy; de-escalation; ticagrelor.

Conflict of interest statement

Conflict of interest: Jacek Kubica — received lecture honoraria from AstraZeneca; Piotr Adamski — none; Piotr Niezgoda — none; Aldona Kubica — received lecture honoraria from AstraZeneca; Przemysław Podhajski — none; Malwina Barańska — none; Julia M. Umińska — none; Łukasz Pietrzykowski — none; Małgorzata Ostrowska — none; Jolanta M. Siller-Matula — received personal fees from Bayer, BMS, Chiesi, and Daiichi, not related to this publication; Jolita Badarienė — received an investigator’s fee and lecture honoraria from AstraZeneca, investigator’s fee from Amgen, and lecture honoraria from Bayer; Stanisław Bartuś — none; Andrzej Budaj — received investigator’s fee, advisory board and lecture honoraria from AstraZeneca, Bayer, Bristol Myers Squibb, Glaxo-SmithKline, Sanofi Aventis, investigator’s fee and lecture honoraria from Novartis, and investigator’s fee from Eisai and Amgen; Sławomir Dobrzycki — none; Łukasz Fidor — none; Mariusz Gąsior — none; Jacek Gessek — none; Marek Gierlotka — none; Robert Gil — none; Jarosław Gorący — none; Paweł Grzelakowski — none; Tomasz Hajdukiewicz — none; Miłosz Jaguszewski — received lecture honoraria from AstraZeneca; Marianna Janion — none; Jarosław Kasprzak — received lecture honoraria from AstraZeneca and Bayer; Adam Kern — none; Artur Klecha — none; Andrzej Kleinrok — none; Wacław Kochman — none; Bartosz Krakowiak — none; Jacek Legutko — received advisory board and lecture honoraria from AstraZeneca and Gedeon Richter; Maciej Lesiak — received speaker and consultancy honoraria from AstraZeneca and Bayer; Marcin Nosal — none; Grzegorz Piotrowski — none; Andrzej Przybylski — none; Tomasz Roleder — none; Grzegorz Skonieczny — none; Grzegorz Sobieszek — none; Agnieszka Tycińska — none; Dariusz Wojciechowski — none; Wojciech Wojakowski — received lecture honoraria from AstraZeneca; Jarosław Wójcik — none; Marzenna Zielińska — none; Aleksander Żurakowski — none; Giuseppe Specchia — none; Diana A. Gorog — received lecture honoraria from AstraZeneca and Boehringer Ingelheim, and a grant from Bayer; Eliano P. Navarese — received grants from Abbott, Amgen, and lecture honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron