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  • Clinical Manifestations of Clopidogrel Hyper-response in Dual Antiplatelet Therapy Following Intracranial Aneurysm Stenting

    Final Number:

    Rajeev D. Sen MD; Christopher Cheng Young MD, MBChB, MSc, PhD; Cory Kelly BS; Isaac Josh Abecassis; Louis J. Kim MD; Michael Robert Levitt MD

    Study Design:

    Subject Category:
    Aneurysm/Subarachnoid Hemorrhage

    Meeting: AANS/CNS Cerebrovascular Section 2018 Annual Meeting

    Introduction: Endovascular stenting of intracranial aneurysms can be complicated by stent thrombosis, To mitigate this risk, patients are prescribed dual anti-platelet therapy (DAPT), typically aspirin and clopidogrel. Clopidogrel prevents thrombosis by inhibiting the P2Y12 adenosine diphosphate (ADP) receptor on the platelet cell membrane. Platelet response to P2Y12 inhibitors has been shown to vary by patient and is determined using the VerifyNow assay. Results are reported in P2Y12 reaction units (PRU), a lower score representing a greater response to the drug. Few studies have examined the clinical effects and management after intracranial aneurysm stenting in patients with a hyper-response to clopidogrel.

    Methods: We performed a single institution, 5-year retrospective review of all patients who underwent endovascular aneurysm treatment that included stenting (stent-assisted coiling and flow-diverting stent placement) and received clopidogrel as part of DAPT (clopidogrel 75mg and aspirin 325mg daily).

    Results: 255 patients underwent endovascular stent procedures and required treatment with DAPT. VerifyNow P2Y12 reaction assay was obtained following preoperative DAPT treatment. VerifyNow PRU <15, indicating a hyper-response, was found in 45 patients. Of these 45 hyper-responders, 7 patients (16%) experienced significant fatigue that resolved by either dose reduction, completion of treatment, or spontaneous improvement over several months. Clopidogrel hyper-response was not associated with aspirin hyper-response or bleeding complications.

    Conclusions: Hyper-response to clopidogrel after intracranial aneurysm stenting may result in symptoms such as fatigue, and dose adjustment may mitigate symptoms and improve patient compliance and satisfaction.

    Patient Care: Our goal is to bring to attention a subpopulation of patients who are hyper-responsive to clopidogrel and subsequently may have some adverse reactions to dual anti-platelet therapy after undergoing endovascular stenting of intracranial aneurysms. We hope that awareness of this phenomenon will lead to an increase in adherence to these important medications as well as in patient satisfaction.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Understand the mechanism of action of anti-platelet agents and their respective activity assays, 2) Identify rates of hyper-response and 3) Identify clinical manifestations of clopidogrel hyper-response.


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