Impact of immature platelets on platelet response to ticagrelor and prasugrel in patients with acute coronary syndrome

Eur Heart J. 2015 Dec 1;36(45):3202-10. doi: 10.1093/eurheartj/ehv326. Epub 2015 Jul 27.

Abstract

Aims: The influence of reticulated platelets (RPs) on platelet inhibition by ticagrelor when compared with prasugrel is unknown. We aimed to determine the influence of RPs on adenosine diphosphate- (ADP-) induced platelet aggregation in patients with acute coronary syndrome who were randomly assigned to receive either ticagrelor or prasugrel for P2Y12 receptor inhibition.

Methods and results: One hundred and twenty-four patients were prospectively enrolled. The immature platelet fraction (IPF) was measured by an automated haematoanalyzer and platelet aggregation was assessed by multiple electrode aggregometry. In a subgroup of patients (n = 28) ADP-induced P-selectin expression was measured in dependence of the time point of study drug intake in RPs that were discriminated from mature platelets by thiazole-orange (TO) staining. The primary endpoint was the correlation of platelet aggregation and IPF in ticagrelor- vs. prasugrel-treated patients. Platelet aggregation significantly correlated with IPF in patients who received prasugrel (r = 0.41, P < 0.001). In contrast, no correlation between IPF and platelet aggregation was observed in ticagrelor-treated patients (r = 0.08, P = 0.51, P for difference of correlation coefficients P = 0.05). Within the TO-positive RP fraction, P-selectin expression was significantly higher in prasugrel when compared with ticagrelor-treated individuals (prasugrel 18.6 ± 16.0% vs. ticagrelor 11.5 ± 6.0%, P = 0.047). A time-dependent P-selectin expression was observed in prasugrel but not in ticagrelor-treated patients (prasugrel early 11.9 ± 9.4% vs. late 26.3 ± 19.0%, P = 0.031, ticagrelor early 9.6 ± 4.9% vs. late 13.5 ± 6.6%, P = 0.127).

Conclusion: Reticulated platelets show a greater impact on platelet reactivity in response to prasugrel when compared with ticagrelor.

Keywords: Acute coronary syndrome; Platelet aggregation; Prasugrel; Reticulated platelets; Ticagrelor.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / drug therapy*
  • Adenosine / analogs & derivatives*
  • Adenosine / therapeutic use
  • Aged
  • Blood Platelets / drug effects*
  • Female
  • Hospitalization
  • Humans
  • Male
  • P-Selectin / metabolism
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prasugrel Hydrochloride / therapeutic use*
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Ticagrelor
  • Treatment Outcome

Substances

  • P-Selectin
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Prasugrel Hydrochloride
  • Ticagrelor
  • Adenosine