Immature Platelet Fraction Predicts Adverse Events in Patients With Acute Coronary Syndrome: the ISAR-REACT 5 Reticulated Platelet Substudy
Dario Bongiovanni, Nina Schreiner, Rosanna Gosetti, Katharina Mayer, Dominick J. Angiolillo, Dirk Sibbing, Stefan Holdenrieder, Aida Anetsberger, Moritz von Scheidt, Heribert Schunkert, Karl‐Ludwig Laugwitz, Stefanie Schüpke, Adnan Kastrati, Isabel Fegers‐Wustrow, Isabell Bernlochner
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 P2Y 12 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 IPF high group included patients with IPF>median and the IPF low 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 IPF high (IPF>3.6%) group compared with the IPF low (IPF ≤ 3.6%) group: 13.0% versus 7.2% (HR adj , 1.74 [1.02–3.00]; P =0.044), independently from the assigned drug ( P int =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.