Clopidogrel versus ticagrelor in high-bleeding risk patients presenting with acute coronary syndromes: insights from the multicenter START-ANTIPLATELET registry

Abstract

Optimal dual antiplatelet therapy (DAPT) strategy in high-bleeding risk (HBR) patients presenting with acute coronary syndrome remains debated. We sought to investigate the use of clopidogrel versus ticagrelor in HBR patients with acute coronary syndrome and their impact on ischemic and bleeding events at 1 year. In the START-ANTIPLATELET registry (NCT02219984), consecutive patients with ≥ 1 HBR criteria were stratified by DAPT type in clopidogrel versus ticagrelor groups. The primary endpoint was net adverse clinical endpoints (NACE), defined as a composite of all-cause death, myocardial infarction, stroke, and major bleeding. Of 1209 patients with 1-year follow-up, 553 were defined at HBR, of whom 383 were considered eligible for the study as on DAPT with clopidogrel (174 or 45.4%) or ticagrelor (209 or 54.6%). Clopidogrel was more often administered in patients at increased ischemic and bleeding risk, while ticagrelor in those undergoing percutaneous coronary intervention. Mean DAPT duration was longer in the ticagrelor group. At 1 year, after multivariate adjustment, no difference in NACEs was observed between patients on clopidogrel versus ticagrelor (19% vs. 11%, adjusted hazard ratio 1.27 [95% CI 0.71–2.27], p = 0.429). Age, number of HBR criteria, and mean DAPT duration were independent predictors of NACEs. In a real-world registry of patients with acute coronary syndrome, 45% were at HBR and frequently treated with clopidogrel. After adjustment for potential confounders, the duration of DAPT, but not DAPT type (stratified by clopidogrel vs. ticagrelor), was associated with the risk of ischemic and bleeding events at 1 year.

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Acknowledgements

The START-ANTIPLATELET Collaborators: Fabio Fimiani, Raffaella Antonia Vitale, Alessandra Schiavo, Marzia Conte, Dario Di Maio: Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy; Daniele Pastori, Danilo Menichelli: I Clinica Medica, Atherothrombosis Centre, Department of Clinical Internal, Anesthesiologic, and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy; Guido Grossi, Luigi Di Serafino: Department of Experimental and Clinical Medicine, Center for Atherothrombotic diseases, University of Florence, Florence, Italy; Vittorio Taglialatela: Department of Advanced Biomedical Sciences, School of Medicine, “Federico II” University, Naples, Italy; Raffaele Galiero, Carlo Acierno: University of Campania “Luigi Vanvitelli” Department of Advanced Medical and Surgical Sciences; Maurizio del Pinto, Giuseppe Gugliemini: Department of Medicine, Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy.

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FG and PC designed the work. FG and EM drafted the manuscript. FG, EM, PC, and PCP worked to the acquisition, analysis, and interpretation of data. All authors revised data critically for important intellectual content, approved the final version, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Paolo Calabrò.

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FG: Research grant from the European Society of Cardiology (ESC). GP: speaker/consultant/advisory board for Amgen, Sanofi, Bayer, Boehringer-Ingelheim, BMS-Pfizer, Daiichi Sankyo, Astra Zeneca, Sigma-Tau, Malesci, PIAM and MSD. IC: speaker for BMS-Pfizer, AstraZeneca, and Boeringher-Ingelheim. Other Authors have no conflicts of interest to disclose.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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The study protocol was approved by the local ethics committees and was conducted in accordance with the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study.

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The list of the START-ANTIPLATELET Collaborators are given in Acknowledgements.

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Gragnano, F., Moscarella, E., Calabrò, P. et al. Clopidogrel versus ticagrelor in high-bleeding risk patients presenting with acute coronary syndromes: insights from the multicenter START-ANTIPLATELET registry. Intern Emerg Med (2020). https://doi.org/10.1007/s11739-020-02404-1

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Keywords

  • Bleeding
  • Dual antiplatelet therapy
  • Clopidogrel
  • Ticagrelor
  • Percutaneous coronary intervention