Ticagrelor or prasugrel in patients with acute coronary syndrome with off-hour versus on-hour presentation: a subgroup analysis of the ISAR-REACT 5 trial

Michael Behnes, Shqipdona Lahu, Gjin Ndrepepa, Maurizio Menichelli, Katharina Mayer, Jochen Wöhrle, Isabell Bernlochner, Senta Gewalt, Bernhard Witzenbichler, Willibald Hochholzer, Dirk Sibbing, Salvatore Cassese, Dominick J Angiolillo, Rayyan Hemetsberger, Christian Valina, Arne Müller, Sebastian Kufner, Christian W Hamm, Erion Xhepa, Alexander Hapfelmeier, Hendrik B Sager, Michael Joner, Massimiliano Fusaro, Gert Richardt, Karl-Ludwig Laugwitz, Franz-Josef Neumann, Heribert Schunkert, Stefanie Schüpke, Adnan Kastrati, Ibrahim Akin, Michael Behnes, Shqipdona Lahu, Gjin Ndrepepa, Maurizio Menichelli, Katharina Mayer, Jochen Wöhrle, Isabell Bernlochner, Senta Gewalt, Bernhard Witzenbichler, Willibald Hochholzer, Dirk Sibbing, Salvatore Cassese, Dominick J Angiolillo, Rayyan Hemetsberger, Christian Valina, Arne Müller, Sebastian Kufner, Christian W Hamm, Erion Xhepa, Alexander Hapfelmeier, Hendrik B Sager, Michael Joner, Massimiliano Fusaro, Gert Richardt, Karl-Ludwig Laugwitz, Franz-Josef Neumann, Heribert Schunkert, Stefanie Schüpke, Adnan Kastrati, Ibrahim Akin

Abstract

Objectives: To assess the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome (ACS) presenting during off- and on-hours.

Background: The efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to time of hospital presentation remain unknown.

Methods: This post hoc analysis of the ISAR-REACT 5 trial included 1565 patients with ACS presenting off-hours and 2453 patients presenting on-hours, randomized to ticagrelor or prasugrel. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium (BARC) type 3-5 bleeding, both at 12 months.

Results: The primary endpoint occurred in 80 patients (10.4%) in the ticagrelor group and 57 patients (7.3%) in the prasugrel group in patients presenting off-hours (hazard ratio [HR] = 1.45; 95% confidence interval [CI] 1.03-2.03; P = 0.033), and 104 patients (8.5%) in the ticagrelor group and 80 patients (6.7%) in the prasugrel group in patients presenting on-hours (HR = 1.29 [0.97-1.73]; P = 0.085), without significant treatment arm-by-presentation time interaction (Pint = 0.62). BARC type 3 to 5 bleeding occurred in 35 patients (5.1%) in the ticagrelor group and 37 patients (5.3%) in the prasugrel group (P = 0.84) in patients presenting off-hours, and 60 patients (5.9%) in the ticagrelor group and 43 patients (4.6%) in the prasugrel group in patients presenting on-hours (P = 0.17).

Conclusions: In patients with ACS planned to undergo an invasive treatment strategy, time of presentation (off-hours vs. on-hours) does not interact significantly with the relative efficacy and safety of ticagrelor vs. prasugrel.

Clinical trial registration: NCT01944800.

Keywords: Acute coronary syndromes; Off-hour presentation; Percutaneous coronary intervention; Prasugrel; Ticagrelor.

Conflict of interest statement

The authors report the following conflicts of interest: Dr. Bernlochner has received lecture fees from Sysmex Europe GmbH; Dr. Hochholzer reports personal fees from Bayer Vital, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Novartis, AstraZeneca, The Medicines Company; Dr. Sibbing has received personal fees from Daichi Sankyo, Sanofi and Astra Zeneca, Bayer, Pfizer and Servier; Dr. Angiolillo reports grants and personal fees from Amgen, Aralez, Astra Zeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Janssen, Merc, Sanofi, CeloNova, personal fees from Haemonetics, PhaseBio, PLx Pharma, Pfizer, The Medicines company, St Jude Medical, grants from CSL Behring, Eisai, Gilead, Idorsia Pharmaceuticals Ltd, Matsutani Chemical Industry Co., Novartis, Osprey Medical, Renal Guard Solutions, Scott R. MacKenzie Foundation; Dr. Hemetsberger received speaker’s honoraria from Boston Scientific; Dr. Kufner reports personal fees from Bristol Myers Squibb, Astra-Zeneca, and Translumina; Dr. Sager reports grants from European Research Council, Else-Kröner-Fresenius-Stiftung, Deutsche Herzstiftung, Deutsche Forschungsgemeinschaft; Dr. Neumann has received personal fees from Amgen, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, and Ferrer; has received grants and personal fees from Pfizer, Biotronik, Edwards Lifesciences, Bayer Healthcare, and Boston Scientific; and has received grants from Medtronic and GlaxoSmithKline outside the submitted work; Dr. Schunkert has received personal fees from Merck Sharp & Dohme, Amgen, Bayer Vital GmbH, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Servier, Brahms, Bristol Myers Squibb, Medtronic, Sanofi, Synlab; and has received grants and personal fees from AstraZeneca; Dr. Schüpke has received the Else Kröner-Memorial grant from the Else Kröner-Fresenius-Stiftung, financial support from the German Center for Cardiovascular Research (DZHK) and consulting fees from Bayer Vital GmbH and lecture fees from Daiichi Sankyo and Biopas Laboratories; Dr. Akin has received lecture fees from Boston Scientific, Boehringer, Daiichi Sankyo, Gore. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
One-year cumulative incidence of the primary endpoint (death, myocardial infarction, or stroke). Left panel: the incidence of the primary endpoint in patients presenting during off-hours. Right panel: the incidence of the primary endpoint in patients presenting during on-hours. Primary endpoint was evaluated in the intention-to-treat population CI confidence interval, HR  hazard ratio
Fig. 2
Fig. 2
Cumulative incidence of the secondary safety endpoint (1-year incidence of Bleeding Academic Research Consortium type 3–5 bleeding). BARC type 3–5 bleeding was evaluated in the modified intention-to-treat population after accounting for the competing risk of death. Results are presented for patients presenting during off-hours (left panel) and on-hours (right panel). BARC Bleeding Academic Research Consortium, CI confidence interval, HR hazard ratio

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