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Long-term pharmacodynamic effects of Ticagrelor versus Clopidogrel in fibrinolytic-treated STEMI patients undergoing early PCI

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Abstract

The long-term pharmacodynamic effects of Ticagrelor versus Clopidogrel in patients undergoing early percutaneous coronary intervention (PCI) after fibrinolytic therapy is unknown. From May 2014 to August 2016, 212 patients undergoing PCI within 24 h of Tenecteplase (TNK), Aspirin, and Clopidogrel for ST-elevated myocardial infarction (STEMI) were randomized at four Canadian sites to receive additional Clopidogrel or Ticagrelor initiated prior to PCI. The platelet reactivity units (PRU) were measured with the VerifyNow Assay before study drug administration (baseline), at 4 and 24 h post PCI, and follow-up appointment. A mixed-model analysis with time as the repeated measure and drug as the between-subjects factor was calculated using 2 separate 1 × 4 ANOVAs, with students t-tests used to compare drugs within each time point. Complete clinical follow-up data (median 115.0 days; IQR 80.3–168.8) was available in 50 patients (23.6%) randomized to either Clopidogrel (n = 23) or Ticagrelor (n = 27). Analyses revealed significant decreases in PRU from baseline to 4 h (261.4 vs. 71.7; Mdiff = − 189.7; p < 0.001) to 24 h (71.7 vs. 27.7; Mdiff = − 44.0; p < 0.001) to end of follow-up (27.7 vs.17.9; Mdiff = − 9.9. p = 0.016) for those randomized to Ticagrelor and significant decreases in PRU only from baseline to 4 h (271.3 vs. 200.8; Mdiff = − 70.5, p = < 0.001) in patients receiving Clopidogrel, and a significantly greater proportion of patients with adequate platelet inhibition (PRU < 208) on long-term follow-up (Clopidogrel, 82.6% vs. Ticagrelor, 100.0%; p = 0.038). Our results demonstrate that in patients undergoing PCI within 24 h of fibrinolysis for STEMI, Ticagrelor provides prolonged platelet inhibition compared with Clopidogrel.

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Funding

This study was made possible by funding provided by AstraZeneca.

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Authors and Affiliations

  1. Prairie Vascular Research Network and Regina Qu’Appelle Health Region, University of Saskatchewan, Regina General Hospital Unit 3A (CCU), Interventional Cardiology Research Office 1440-14th Ave., Regina, SK, Canada

    Andrew Yang, Quin Pon, Andrea Lavoie, Jennifer J. Crawford, Sebastian Harenberg, Rodney H. Zimmermann, Jeff Booker, Sheila Kelly & Payam Dehghani

  2. London Health Sciences, University of London, London, ON, Canada

    Shahar Lavi

  3. Southlake Regional Health Centre, University of Toronto, Newmarket, ON, Canada

    Warren J. Cantor

  4. Hamilton Health Sciences, McMaster University, Hamilton, ON, Canada

    Shamir R. Mehta

  5. Terrence Donnelly Heart Centre, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada

    Akshay Bagai, Shaun G. Goodman & Asim N. Cheema

Authors
  1. Andrew Yang
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  2. Quin Pon
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  3. Andrea Lavoie
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  4. Jennifer J. Crawford
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  5. Sebastian Harenberg
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  6. Rodney H. Zimmermann
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  7. Jeff Booker
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  8. Sheila Kelly
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  9. Shahar Lavi
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  10. Warren J. Cantor
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  11. Shamir R. Mehta
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  14. Asim N. Cheema
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  15. Payam Dehghani
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Corresponding author

Correspondence to Payam Dehghani.

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Conflict of interest

Andrew Yang, Quin Pon, Jennifer Crawford, Sebastian Harenberg, Sheila Kelly, and Shamir R. Mehta have no conflicts of interest. Payam Dehghani has received significant research grant, and modest speaking honoraria from Astra Zeneca. Andrea Lavoie has received modest speaking honoraria from Astra Zeneca. Rodney Zimmermann has has received modest speaking honoraria from Astra Zeneca. Jeff Booker has received modest speaking honoraria from Astra Zeneca. Shahar Lavi has received significant research grant from Astra Zeneca. Warren J Cantor has participated in advisory boards and has received modest speaking honoraria. Akshay Bagai has received modest honoraria for speaking/consulting from Astra Zeneca. Shaun Goodman reports significant research grant support and modest speaker/consulting honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb/Sanofi, Daiichi-Sankyo, and Lilly. Asim Cheema has received significant research grant from Astra Zeneca.

Ethical approval

The study complied with the Declaration of Helsinki and with International Conference on Harmonization/Good Clinical Practice guidelines, and was approved by local ethics board of all the participating institutions.

Informed consent

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

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Yang, A., Pon, Q., Lavoie, A. et al. Long-term pharmacodynamic effects of Ticagrelor versus Clopidogrel in fibrinolytic-treated STEMI patients undergoing early PCI. J Thromb Thrombolysis 45, 225–233 (2018). https://doi.org/10.1007/s11239-017-1581-2

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  • DOI: https://doi.org/10.1007/s11239-017-1581-2

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