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Facilitation Through Aggrastat or Cangrelor Bolus and Infusion Over PrasugreL: a MUlticenter Randomized Open-label Trial in PatientS with ST-elevation Myocardial InFarction Referred for PrimAry PercutaneouS InTERvention (FABOLUS FASTER) Trial: Design and Rationale

The FABOLUS FASTER Trial

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Abstract

Antithrombotic therapy is a critical component of the management of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Rapid and profound inhibition of platelet reactivity has been shown to mitigate the ischemic risks and improve myocardial salvage. High residual platelet reactivity (HRPR) has been reported up to 4 or 6 h after loading dose of prasugrel or ticagrelor; therefore, multiple alternative strategies, including crushed or chewed oral tables or intravenous agents, have been investigated to provide a more rapid and sustained inhibition of platelet function and bridge the initial treatment gap. The FABOLUS FASTER is the first investigator-initiated, multicentre, open-label, prospective, randomized study to directly compare the pharmacodynamics effects of cangrelor, tirofiban, chewed or integer prasugrel. This study will add new insights in the management of antiplatelet therapy in patients with STEMI undergoing primary PCI and might be hypothesis-generating for future clinical trials in this field. The trial is registered on clinicaltrials.gov NCT02978040, and EudraCT 2017-001065-24.

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Abbreviations

AAR:

Area at risk

AUC:

Area under the curve

ACS:

Acute coronary syndrome

ACT:

Activated clotting time

ADP:

Adenosine diphosphate

ATP:

Adenosine triphosphate

cMRI:

Magnetic resonance imaging

ECG:

Electrocardiogram

HPRP:

High residual platelet reactivity

IPA:

Inhibition of platelet activity

LTA:

Light transmittance aggregometry

MS:

Myocardial salvage

MSI:

Myocardial salvage index

MVO:

Microvascular obstruction

PAM:

Prasugrel active metabolite

PCI:

Percutaneous coronary intervention

PD:

Pharmacodynamic

PK:

Pharmacokinetic

STEMI:

ST-elevation myocardial infarction

UFH:

Unfractionated heparin

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Funding

This study is an Investigator-Initiated Trial supported by a grant to the institution (Inselspital, University of Bern) from Medicure Inc., 2-1250 Waverley Street, Winnipeg, Manitoba, CANADA R3T 6C6.

Author information

Authors and Affiliations

  1. Department of Cardiology, Bern University Hospital, CH-3010, Bern, Switzerland

    Giuseppe Gargiulo, Felice Gragnano, Negar Manavifar, Andreas Wahl, Lukas Hunziker, Michael Billinger, Stephan Windecker & Marco Valgimigli

  2. Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy

    Giuseppe Gargiulo, Giovanni Esposito, Plinio Cirillo, Raffaele Piccolo & Marisa Avvedimento

  3. University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Michael Nagler

  4. Department of Medicine, Unit of General Medicine for the Study and Treatment of Hypertensive Disease, University of Verona, Policlinico GB Rossi, Verona, Italy

    Pietro Minuz

  5. Cardiology Unit, Azienda Ospedaliera Universitaria di Ferrara, Cona, FE, Italy

    Gianluca Campo & Matteo Tebaldi

  6. Maria Cecilia Hospital, GVM Care & Research, Cotignola, RA, Italy

    Gianluca Campo

  7. Clinical Trials Unit (CTU) Bern, University of Bern, Bern, Switzerland

    Dik Heg

Authors
  1. Giuseppe Gargiulo
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  2. Giovanni Esposito
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Corresponding author

Correspondence to Marco Valgimigli.

Ethics declarations

Ethics Approval

The study was approved by the local Ethics Committees (“Kantonale Ethikkommission Bern (KEK)” for Bern, Switzerland; “Comitato Etico Università Federico II” for Naples and “Comitato Etico Area Vasta Emilia Centro - AVEC” for Ferrara, Italy) and the Italian Agency of the Drug (AIFA).

Human Subjects/Informed Consent Statement

All procedures followed are in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent is obtained from all patients previous to being included in the study.

Conflict of Interest

FG reports research grant support from the European Society of Cardiology (ESC Research grant).

SW reports research and educational grants from Abbott, Amgen, Bayer, BMS, Boston Scientific, Biotronik, CSL Behring, Edwards Lifesciences, Medtronic, Polares and Sinomed, outside the submitted work.

MV reports grants and personal fees from Abbott, Alvimedica, Amgen, Bayer, Bristol-Myers Squibb SA, Coreflow, Daiichi Sankyo, Vifor, Idorsia, Terumo, iVascular and AstraZeneca, outside the submitted work.

Other authors have nothing to disclose.

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Associate Editor Emanuele Barbato oversaw the review of this article

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Gargiulo, G., Esposito, G., Cirillo, P. et al. Facilitation Through Aggrastat or Cangrelor Bolus and Infusion Over PrasugreL: a MUlticenter Randomized Open-label Trial in PatientS with ST-elevation Myocardial InFarction Referred for PrimAry PercutaneouS InTERvention (FABOLUS FASTER) Trial: Design and Rationale. J. of Cardiovasc. Trans. Res. 14, 110–119 (2021). https://doi.org/10.1007/s12265-020-09969-4

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