High On-Treatment Platelet Reactivity in Danish Hyper-Acute Ischaemic Stroke Patients

For you to figure out applicability to your next stroke. Hope you are conscious in the emergency room. 

High On-Treatment Platelet Reactivity in Danish Hyper-Acute Ischaemic Stroke Patients

Charlotte L. Rath^1*, Niklas Rye Jørgensen^2,3 and Troels Wienecke^1,4

• ¹Department of Neurology, Neurovascular Centre, Zealand University Hospital, Roskilde, Denmark
• ²Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
• ³OPEN, Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
• ⁴Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

Objective: Early anti-platelet therapy is a cornerstone in the prevention of recurrent ischaemic stroke (IS) and transient ischaemic attacks (TIAs), although the responsiveness to anti-platelet medications varies among patients. Several studies have reported that patients with ischaemic stroke who exhibit high on-treatment platelet reactivity (HTPR) 5–10 days after antiplatelet medication onset, have an increased risk of vascular events. In this study we aim to determine the prevalence of HTPR in the hyper-acute stroke phase less than 48 h from symptom onset, after the administration of a 300 mg bolus of oral clopidogrel in a real-world setting in Danish IS and TIA patients.

Material and Methods: In total, 219 Danish patients with acute IS or TIA received 300 mg of oral clopidogrel on admission. Blood samples from all patients were analyzed using the VerifyNow P2Y12 system at 8–24 h after clopidogrel intake. Concomitant therapy and the intervals between ictus and blood collection, clopidogrel intake and blood collection, and blood sampling and analysis were recorded for all patients.

Results: HTPR in the hyper-acute stroke phase was observed in 28.8% (63/219) samples. After adjustment for age, sex, co-morbidities, and co-medications, none of the tested variables exhibited an association with HTPR or the platelet reaction unit value measured using the VerifyNow P2Y12 system.

Conclusions: The recognition of HTPR to specific anti-platelet agents in the hyper-acute phase after stroke may be the first step toward interventions that may further minimize the early recurrent stroke risk. Further large randomized trials including clinical outcome assessments are necessary.

Introduction

Anti-platelet therapy is a cornerstone in the prevention of secondary ischaemic stroke (IS), and clopidogrel has been reported to lower the long-term risk of recurrent stroke with the same efficiency as acetylsalicylic acid combined with dipyridamole (1). Patients with a transient ischaemic attack (TIA) exhibit an increased stroke risk in the acute phase (2) although this risk is lowered after treatment with anti-platelet agents (3). The importance of very early treatment in both acute IS and TIA has been further established in a recent time-course analysis of existing randomized trials (4). However, the platelet function was not explored in these studies. Although the prevalence of patients with IS who exhibit high on treatment platelet reactivity (HTPR), also known as non-responders, has been evaluated in several other studies, the results have been highly variable (8–61%) (5).

Clopidogrel is an anti-platelet aggregation drug that inhibits adenosine 5-diphosphate from binding to its P2Y12 receptor on the surface of the platelet, resulting in the inhibition of platelet reactivity. This pro-drug requires biotransformation (two-step oxidation) that is catalyzed by several cytochrome P450 (CYP) enzymes. A previous study recommended that platelet reactivity should be tested at 8 h after the administration of a loading dose of 300 mg (6).

In a recent meta-analysis, it was found that the recurrent stroke or TIA risk was significantly higher in patients with HTPR (RR = 1.81), and that the HTPR prevalence after clopidogrel administration was 27% (7). However, the studies included in this meta-analysis differed with regard to the ethnicity of patients, treatment regimen, HTPR assessment technique, and treatment period at the time of HTPR testing. And importantly, the studies evaluated HTPR >3 days after treatment start.

The aim of the present study was to establish the prevalence of HTPR at 8–24 h after the intake of clopidogrel 300 mg in the acute phase (lt;48 h after symptom onset) after IS or TIA in a real-world setting.