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  • P2Y12 Precision in Therapeutic Monitoring of Dual Anti-Platelet Therapy for Flow Diversion of Cerebral Aneurysms

    Final Number:

    David A. Zarrin BS; Jessica K. Campos MD; Matthew T Bender MD; Bowen Jiang MD; Chau D. Vo BA; Arun Chandra BS; Justin M. Caplan MD; Judy Huang MD; Rafael Jesus Tamargo MD; Li-Mei Lin BA; Geoffrey P. Colby MD, PhD; Alexander L. Coon MD

    Study Design:

    Subject Category:
    Basic Science

    Meeting: AANS/CNS Cerebrovascular Section 2018 Annual Meeting

    Introduction: Dual antiplatelet therapy (DAT), most commonly consisting of aspirin and clopidogrel, is the standard of care for intracranial stenting procedures, including flow diversion. Clopidogrel response varies by individual. We sought to investigate the real-world precision of P2Y12 assessment of clopidogrel response.

    Methods: A prospectively-collected, IRB-approved cerebral aneurysm database was reviewed to identify 588 patients who were treated with the Pipeline Embolization Device (PED) from 2011-2017. Patients with multiple P2Y12 assays drawn within a 24-hour window were identified. A single patient could contribute multiple, independent 24-hour sets. Levels drawn before a 5-day course of DAT were excluded. Patients who received alternative antiplatelet agents, including abciximab and prasugrel, were excluded. Therapeutic range was defined as P2Y12 from 60-200.

    Results: A total of 1460 P2Y12 measurements were recorded across all patients; 261 (44%) patients had more than one assay drawn. A total of 121 (21%) patients had multiple P2Y12 measurements (range 2-3) within 24 hours. These 121 patients accounted for 206 independent 24-hour sets of P2Y12 measurements. The average P2Y12 fluctuation across all sets was 36 points. The 24-hour set P2Y12 fluctuation of the 25th , 50th , and 75th-percentiles were 11 points, 28 points, and 48 points respectively. Of the 206, 24-hour sets, P2Y12 assays, 75% remained within their original therapeutic category: 88 (43%) all therapeutic, 49 (24%) all hypo-responsive, and 18 (9%) all hyper-responsive. Twenty-five percent of patients fluctuated between therapeutic categories when multiple P2Y12 assessments were drawn within a 24-hour period: 23 (11%) between hypo-response and therapeutic, 25 (12%) between hyper-response and therapeutic, and 3 (1%) between hypo-response and hyper-response.

    Conclusions: There is controversy about the utility of P2Y12 assessment of therapeutic response to clopidogrel. Our experience suggests P2Y12 is an often-imprecise measure, and this should be considered when utilizing P2Y12 levels for clinical decisions.

    Patient Care: P2Y12 inhibition assessment assays are formative in directing anti-platelet (clopidogrel) regimens following endovascular procedures. This study addresses the imprecision of the P2Y12 inhibition assay in determining therapeutic response, to both (1) improve the understanding of the assay's utility in clinical decisions and (2) address the clinical ramifications of titrating post-procedural clopidogrel regimens in a patient population of varied clopidogrel hypo- and hyper-responders.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the indications for obtaining P2Y12 inhibition assays and its role in titrating post-endovascular procedure anti-platelet medication regimens; 2) Discuss, in small groups, the controversies of utilizing P2Y12 reactivity units (PRU) to titrate clopidogrel dosing regimens; 3) Describe the intra-individual PRU variance seen in patients within this study; and 4) Describe the clinical ramifications of titrating clopidogrel dosing-regimens to PRU levels.

    References: 1. Bender MT, Lin LM, Colby GP, Lubelski D, Huang J, Tamargo RJ, Coon AL. P2Y12 hyporesponse (PRU>200) is not associated with increased thromboembolic complications in anterior circulation Pipeline. J Neurointerv Surg. 2017 Oct;9(10):978-981. doi: 10.1136/neurintsurg-2016-012618. Epub 2016 Sep 6.

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