Key result
Cangrelor bolus achieves sufficient platelet inhibition in ~90% of healthy volunteers, maintained by continuous infusion.
Why the study?
High on-treatment platelet reactivity remains a major problem in acute STEMI management, prompting investigation of a novel prehospital cangrelor treatment strategy tested in healthy volunteers.
Does cangrelor administered via bolus and continuous infusion using an IV flow regulator provide sufficient platelet inhibition in healthy volunteers?
Does cangrelor administered via bolus and continuous infusion using an IV flow regulator provide sufficient platelet inhibition in healthy volunteers?
Weight-adapted bolus followed by continuous infusion of cangrelor via an IV flow regulator provides immediate and sustained platelet inhibition, suggesting a feasible prehospital strategy for acute STEMI management.
Supports prehospital cangrelor strategies in STEMI; extends RCT evidence on platelet inhibition to simplified field administration but requires patient confirmation.
BACKGROUND: High on-treatment platelet reactivity (HTPR) remains a major problem in the acute management of ST-elevation myocardial infarction (STEMI), leading to higher rates of stent thrombosis and mortality. We aimed to investigate a novel, prehospital treatment strategy using cangrelor and tested its pharmacodynamic effects in a model using healthy volunteers. METHODS: We conducted a dose-finding, open-label, pilot trial including 12 healthy volunteers and tested three ascending bolus infusions of cangrelor (5 mg, 10 mg and 20 mg) and a bolus infusion followed by a continuous infusion via an intravenous (IV) flow regulator. Platelet function was assessed using multiple electrode aggregometry (MEA), vasodilator-stimulated phosphoprotein phosphorylation assay (VASP-P) and the platelet function analyzer. In an ex vivo experiment, epinephrine was used to counteract the antiplatelet effect of cangrelor. RESULTS: All cangrelor bolus infusions resulted in immediate and pronounced platelet inhibition. Bolus infusions of cangrelor 20 mg resulted in sufficient platelet inhibition assessed by MEA for 20 min in 90% of subjects. Infusion of cangrelor via the IV flow regulator resulted in sufficient platelet inhibition throughout the course of administration. Ex vivo epinephrine, in concentrations of 200 and 500 ng/mL was able to partially reverse the antiplatelet effect of cangrelor in a dose-dependent manner. CONCLUSIONS: Weight-adapted bolus infusions followed by a continuous infusion of cangrelor via IV flow regulator result in immediate and pronounced platelet inhibition in healthy subjects. Cangrelor given as weight-adapted bolus infusion followed by a continuous infusion using an IV flow regulator may be a viable treatment approach for effective and well controllable prehospital platelet inhibition. TRIAL REGISTRATION: EC (Medical University of Vienna) 1835/2019 and EudraCT 2019-002792-34 .
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Gelbenegger et al. (2022) studied Healthy volunteers (n=12). Cangrelor was evaluated on Platelet inhibition assessed by multiple electrode aggregometry. Bolus infusions of cangrelor 20 mg resulted in sufficient platelet inhibition for 20 min in 90% of healthy volunteers, and continuous infusion maintained this effect.
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