Response to prasugrel and levels of circulating reticulated platelets in patients with ST-segment elevation myocardial infarction.

Abstract

OBJECTIVES:

The aim of this study was to determine whether response to prasugrel is associated with the proportion of circulating reticulated platelets (RPs) in patients with ST-segment elevation myocardial infarction (STEMI).

BACKGROUND:

Despite better pharmacodynamic properties and clinical efficacy of prasugrel compared with clopidogrel, antiplatelet responses to prasugrel are not uniform. The mechanism of this variability in response is not clear. RPs, young hyperactive forms, are increased during situations of enhanced platelet turnover.

METHODS:

Patients with STEMI treated with primary percutaneous intervention (PCI) and prasugrel were tested for platelet reactivity using purinergic receptor P₂Y, G-protein coupled, 12 (P₂Y₁₂) assay and multiple electrode aggregometry (MEA). RP levels were determined using flow cytometry with thiazole orange staining. Tests were performed at 2 to 4 days and 30 days post-PCI. Platelet function was compared by varying levels of RPs, analyzed as continuous (regression analysis) and categorical (tertiles) variables.

RESULTS:

Sixty-two patients were included (mean age: 57.5 ± 8 years; 21.2% women; 27.7% diabetes). At the early time point, RP levels were strongly correlated with platelet reactivity when evaluated by the P₂Y₁₂ assay (Spearman's correlation coefficient: 0.55 for P₂Y₁₂ reaction units, -0.49 for percent inhibition) and MEA (Spearman's: 0.50). The upper tertile of RPs displayed higher platelet reactivity compared with the middle and lower tertiles, according to P₂Y₁₂ assay and MEA. Similar results with strong correlations between RP and platelet reactivity were noted at 30 days post-PCI.

CONCLUSIONS:

The proportion of circulating RPs strongly correlates with response to prasugrel in patients with STEMI treated with PCI. High levels of RPs are associated with increased platelet reactivity despite prasugrel treatment.

• Authors: Leor Perl, Hila Lerman-Shivek, Eldad Rechavia, Muthiah Vaduganathan, Dorit Leshem-Lev, Noa Zemer-Wassercug, Oshrat Dadush, Pablo Codner, Tamir Bental, Alexander Battler, Ran Kornowski, Eli I Lev
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 63 Issue 6 Pg. 513-7 (Feb 18 2014) ISSN: 1558-3597 [Electronic] United States
• PMID: 24148715 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Piperazines
• Purinergic P2Y Receptor Antagonists
• Thiophenes
• Prasugrel Hydrochloride

Topics

• Aged
• Blood Platelets (drug effects)
• Female
• Humans
• Male
• Middle Aged
• Myocardial Infarction (blood, drug therapy, surgery)
• Percutaneous Coronary Intervention
• Piperazines (pharmacology, therapeutic use)
• Prasugrel Hydrochloride
• Purinergic P2Y Receptor Antagonists (pharmacology, therapeutic use)
• Thiophenes (pharmacology, therapeutic use)