Immature Platelet Fraction Predicts Adverse Events in Patients With Acute Coronary Syndrome: the ISAR-REACT 5 Reticulated Platelet Substudy

Arterioscler Thromb Vasc Biol. 2023 Feb;43(2):e83-e93. doi: 10.1161/ATVBAHA.122.318614. Epub 2022 Dec 22.

Abstract

Background: Immature or reticulated platelets are associated with impaired efficacy of antiplatelet drugs and adverse events in cardiovascular patients. Their role as a predictive biomarker in patients with acute coronary syndrome treated with potent P2Y12 receptor inhibitors is not fully understood. We aimed to prospectively evaluate reticulated platelets as a predictor of the primary end point of the ISAR-REACT 5 trial consisting of death, myocardial infarction, or stroke at 1 year in patients with acute coronary syndrome randomized to prasugrel or ticagrelor.

Methods: Immature platelet fraction (IPF) was assessed within 48 hours after randomization. Patients were divided based on the IPF median values: the IPFhigh group included patients with IPF>median and the IPFlow group included patients with IPF≤median. Platelet aggregation was assessed using the Multiplate Analyzer and was correlated to IPF.

Results: Five hundred seventy-seven patients were included in the study. IPF values in % (median [interquartile range]) within the first 48 hours did not differ between the two study groups: 3.6 (2.5-5.2)% in the prasugrel group and 3.6 (2.5-5.4)% in the ticagrelor group (P=0.882). The incidence of the primary end point was significantly higher in the IPFhigh (IPF>3.6%) group compared with the IPFlow (IPF≤3.6%) group: 13.0% versus 7.2% (HRadj, 1.74 [1.02-3.00]; P=0.044), independently from the assigned drug (Pint=0.159). No significant association between IPF and BARC 3 to 5 bleeding was observed. ADP-induced platelet aggregation correlated significantly with IPF in patients treated with prasugrel (r=0.22; P=0.005) while no correlation was detected in patients treated with ticagrelor (r=0.09; P=0.257).

Conclusions: Independently from drug treatment, IPF was associated with the primary end point and therefore is a promising biomarker for the prediction of adverse cardiovascular events in patients with acute coronary syndrome treated with prasugrel or ticagrelor.

Registration: https://www.

Clinicaltrials: gov; Unique identifier: NCT01944800.

Keywords: acute coronary syndrome; biomarker; cardiovascular events; drug; immature platelets; reticulated platelets.

Publication types

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

MeSH terms

  • Acute Coronary Syndrome* / diagnosis
  • Acute Coronary Syndrome* / drug therapy
  • Blood Platelets
  • Humans
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation Inhibitors / adverse effects
  • Prasugrel Hydrochloride / adverse effects
  • Ticagrelor / adverse effects
  • Treatment Outcome

Substances

  • Ticagrelor
  • Prasugrel Hydrochloride
  • Platelet Aggregation Inhibitors

Associated data

  • ClinicalTrials.gov/NCT01944800