Immature platelet fraction is a strong predictor of adverse cardiovascular events in patients with acute coronary syndrome. Results of the ISAR-REACT 5 reticulated platelet substudy

Abstract Introduction Reticulated or immature Platelets are pro-thrombotic RNA-rich young platelets, which have been reported to correlate with adverse events in several pathological settings including coronary artery disease. However, the predictive value of this subgroup of platelets in patients with acute coronary syndrome treated with the potent novel P2Y12 inhibitors prasugrel or ticagrelor has not been investigated yet. Moreover, their role as predictors of major bleeding is unclear. Purpose The primary aim of this prespecified reticulated platelet ISAR-REACT-5 substudy was to evaluate the immature platelet fraction (IPF%) in peripheral blood as a predictor of the composite primary endpoint consisting of death, myocardial infarction, or stroke at one year after randomization in patients with acute coronary syndrome. Methods IPF was assessed in the first 24h after randomization using a fully automated system and correlated to the incidence of the primary endpoint. All patients with available IPF values were included. The Sysmex system uses two fluorescent dyes to stain platelet RNA and a computer algorithm (Sysmex IPF Master) discriminates immature from mature platelets by the intensity of forward scattered light and fluorescence. The immature platelet fraction is displayed as percentage of the total optical platelet count (IPF%). Results IPF values within the first 24h after randomization were available in a total of 506 randomized patients. Baseline characteristics and IPF (median [IQR]) values did not differ between the 2 study groups (IPF: prasugrel 3.9% [2.7–5.8] ticagrelor 3.4% [2.5–5.6] p=0.56). Significantly higher IPF values were observed in patients reaching the primary endpoint (n=55 of 506) independent from the study group (p for interaction= 0.28). ROC-curve analysis revealed a cut-of value of IPF 3.6% for the prediction of death, myocardial infarction or stroke with a Hazard ratio (HR) according to cox-regression analysis of 1.98 (95% CI, 1.15–3.44), P=0.01 (Figure 1A). Interestingly, we also detected a trend for higher major bleedings (BARC 3–5) in patients with elevated IPF values above IPF>4.8% according to ROC-curve analysis (Figure 1B). Conclusion IPF was significantly associated with the primary endpoint in the ISAR-REACT 5 substudy independent from the treatment group and therefore is a promising novel biomarker for the prediction of adverse cardiovascular events in patients with acute coronary syndrome. Figure 1 Funding Acknowled