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Platelet Inhibition with Ticagrelor 60 mg Versus 90 mg Twice Daily in Elderly Patients with Acute Coronary Syndrome: Rationale and Design of the PLINY THE ELDER Trial

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Abstract

Background

Elderly status is steadily increasing among patients with acute coronary syndrome (ACS). Dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 receptor inhibitor is the cornerstone of treatment to prevent recurrent thrombotic complications in patients with ACS. However, DAPT in older patients is challenged by a concurrent heightened risk of ischemia and bleeding. The aim of this study is to evaluate the pharmacodynamic and pharmacokinetic profile of a lower dose of ticagrelor (60 mg twice daily) among elderly patients during the early phase of ACS.

Study Design

PLINY THE ELDER (PLatelet INhibition with two different doses of potent P2y12 inhibitors in THE ELDERly population) (NCT04739384) is a prospective, randomized, open-label, crossover trial to evaluate the non-inferiority of a lower dose of ticagrelor (60 mg twice daily) compared with a standard dose (90 mg twice daily) among elderly patients with ACS undergoing percutaneous coronary intervention (PCI). A total of 50 patients, aged 75 years or more, with indication to potent P2Y12 receptor inhibitors will be randomized within 3 days from PCI for the index ACS. Patients with indication to oral anticoagulant therapy, treatment with glycoprotein IIb/IIIa inhibitors, or active bleeding will be excluded. The primary endpoint is platelet reactivity determined by P2Y12 reaction units (PRU) (VerifyNow, Accumetrics, San Diego, CA, USA) after treatment with ticagrelor 60 or 90 mg twice daily for 14 days. Secondary endpoints will include other pharmacodynamic tests of ADP-induced aggregation (light transmittance aggregometry and multiple electrode aggregometry) and determination of pharmacokinetic profile (plasma levels of ticagrelor and its metabolite AR-C124910XX) by high performance liquid chromatography-tandem mass spectrometry.

Conclusions

The PLINY THE ELDER trial will determine whether a lower dose of ticagrelor confers non-inferior platelet inhibition compared with the standard dose in the early phase of ACS among elderly patients undergoing PCI, informing future clinical investigation.

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Data Availability

The Electronic data capture was designed by the investigators and Web-implemented in REDCap.

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Acknowledgements

Roberta Paolillo and Attilio Leone are supported by a research grant provided by the Cardiopath PhD program.

Funding

The University of Naples Federico II is the sponsor of the trial and there is no external funding for this trial.

Author information

Authors and Affiliations

  1. Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples Federico II, Naples, Italy

    Raffaele Piccolo, Marisa Avvedimento, Mario Enrico Canonico, Paola Gargiulo, Roberta Paolillo, Carmine Morisco, Fiorenzo Simonetti, Attilio Leone, Alessandra Marenna, Giuseppe Gargiulo, Eugenio Stabile, Luigi Di Serafino, Anna Franzone, Plinio Cirillo & Giovanni Esposito

  2. Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana”, University of Salerno, Baronissi, SA, Italy

    Valeria Conti, Fabrizio Dal Piaz & Amelia Filippelli

  3. Department of Clinical Pharmacology and Pharmacogenetics Unit, University Hospital “San Giovanni Di Dio E Ruggi d’Aragona”, Salerno, Italy

    Valeria Conti, Fabrizio Dal Piaz & Amelia Filippelli

  4. Department of Public Health, University of Naples Federico II, Naples, Italy

    Dario Bruzzese

  5. UNESCO Chair On Health Education and Sustainable Development, University of Naples Federico II, Naples, Italy

    Giovanni Esposito

Authors
  1. Raffaele Piccolo
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  2. Marisa Avvedimento
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  3. Mario Enrico Canonico
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  4. Paola Gargiulo
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  5. Roberta Paolillo
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  6. Valeria Conti
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  7. Fabrizio Dal Piaz
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  8. Amelia Filippelli
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  9. Carmine Morisco
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  10. Fiorenzo Simonetti
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  11. Attilio Leone
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  12. Alessandra Marenna
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  13. Dario Bruzzese
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  14. Giuseppe Gargiulo
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  15. Eugenio Stabile
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  16. Luigi Di Serafino
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  17. Anna Franzone
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  18. Plinio Cirillo
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  19. Giovanni Esposito
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Contributions

Study design (RaPi, GE); study conduction and patients recruitment (RaPi, MA, MEC, RP, FS, PG, CM, AL, AM), methodology and sample size calculation (DB); writing (original draft preparation) (RaPi, MA); writing (review and editing) (RaPi, PG, VC, FDP, AF, CM); funding (GE; PI); supervision (RaPi, GG, ES, LDS, AF, PC). All authors read and approved this manuscript.

Corresponding author

Correspondence to Raffaele Piccolo.

Ethics declarations

Ethics Approval

The final study protocol and informed consent have been reviewed and approved by the institutional ethics committee and by the Italian Medicines Agency (EudraCT 2019–002391-13). This study is conducted according to the principles of the Declaration of Helsinki.

Informed Consent

Informed consent will be obtained from all individual participants included in the study. The final study protocol and informed consent have been reviewed and approved by the institutional ethics committee and by the Italian Medicines Agency (EudraCT 2019–002391-13).

Consent for Publication

Not applicable.

Conflict of Interest

Dr. Piccolo reports personal fees from Abbott Vascular, Biotronik, and Daiichi-Sankyo, outside the submitted work. Dr. Gargiulo G reports personal fees from Daiichi-Sankyo, outside the submitted work. Dr. Di Serafino reports personal fees from Abbott Vascular and Hexacath, outside the submitted work. Dr. Esposito reports personal fees from Abbott Vascular, Amgen, Edwards Lifesciences, and Sanofi, outside the submitted work and research grants to the institution from Alvimedica, Boston Scientific, and Medtronic. The other authors have no conflicts of interest to declare.

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Clinical Trial Registration: EudraCT 2019–002,391-13. Clinicaltrials.gov NCT04739384

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Piccolo, R., Avvedimento, M., Canonico, M.E. et al. Platelet Inhibition with Ticagrelor 60 mg Versus 90 mg Twice Daily in Elderly Patients with Acute Coronary Syndrome: Rationale and Design of the PLINY THE ELDER Trial. Cardiovasc Drugs Ther 37, 1031–1038 (2023). https://doi.org/10.1007/s10557-021-07302-y

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  • DOI: https://doi.org/10.1007/s10557-021-07302-y

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