5915Diurnal variability of on-treatment platelet reactivity in clopidogrel vs. prasugrel treated acute coronary syndrome patients: a pre-specified TROPICAL-ACS sub-study

Abstract

Background: Long‐term evidence supports a clustering of cardiovascular events in the early morning hours and smaller mechanistic studies in aspirin‐treated patients have shown increased platelet reactivity at the end of the dosing interval. Comparative pharmacodynamic analyses for different adenosine‐diphosphate (ADP) receptor inhibitors in percutaneous coronary intervention (PCI)‐treated acute coronary syndrome (ACS) patients are lacking and this pre‐specified analysis of the randomized TROPICAL‐ACS trial aimed at investigating diurnal variability of on‐treatment platelet reactivity in clopidogrel vs. prasugrel treated patients. Material and methods: The investigator‐initiated TROPICAL‐ACS trial randomized 2610 biomarker‐positive ACS patients 1:1 to either standard treatment with prasugrel (10 or 5 mg/d, control group) or to a platelet function testing guided deescalation of antiplatelet treatment with a switch to clopidogrel (75 mg/d, guided de‐escalation group). This study design enabled a diurnal comparison of onprasugrel vs. on‐clopidogrel treatment platelet reactivity under steady‐state conditions. For 2526 ACS patients (97%), both the exact time of blood sampling and the ADP‐induced platelet aggregation value (assessed in units on the Multiplate analyzer) were available. These patients constitute the study cohort for this prespecified analysis. Results: The mean age of patients was 58.6 (±10.1) years and 535 (21.2%) were female. Platelet function in patients on clopidogrel (n=1265) was subject to significant diurnal variability (p=0.019) with a peaking of platelet reactivity in the early morning hours (5‐10 am). In prasugrel treated patients (n=1261) there was no sign for diurnal variability (p=0.174) (see Figure). Conclusions: The potent ADP receptor inhibitor prasugrel is not subject to diurnal variability while we observed a significant diurnal variability of on‐clopidogrel platelet reactivity in ACS patients. The clinical impact of this observation may differ for patients with and without an adequate response to clopidogrel treatment and the issue of diurnal variability of platelet reactivity in ACS patients undergoing PCI warrants further investigation. (Figure Presented) .