Clopidogrel hyper-response increases peripheral hemorrhagic complications without increasing intracranial complications in endovascular aneurysm treatments requiring dual antiplatelet therapy

Christopher C Young; David I Bass; Michael J Cruz; Kate Carroll; Kevin N Vanent; Chungeun Lee; Rajeev D Sen; Abdullah H Feroze; John R Williams; Samuel Levy; Denzel McCray; Cory M Kelly; Jason Barber; Louis J Kim; Michael R Levitt

doi:10.1016/j.jocn.2022.09.005

Clopidogrel hyper-response increases peripheral hemorrhagic complications without increasing intracranial complications in endovascular aneurysm treatments requiring dual antiplatelet therapy

J Clin Neurosci. 2022 Nov:105:66-72. doi: 10.1016/j.jocn.2022.09.005. Epub 2022 Sep 13.

Authors

Affiliations

¹ Department of Neurological Surgery, University of Washington, Seattle, WA 98104, USA.
² School of Medicine, University of Washington, Seattle, WA 98104, USA.
³ School of Medicine, Washington State University, Spokane, WA 99202, USA.
⁴ Department of Neurological Surgery, University of Washington, Seattle, WA 98104, USA; Stroke & Applied Neurosciences Center, University of Washington, Seattle, WA 98104, USA.
⁵ Stroke & Applied Neurosciences Center, University of Washington, Seattle, WA 98104, USA.
⁶ Department of Neurological Surgery, University of Washington, Seattle, WA 98104, USA; Stroke & Applied Neurosciences Center, University of Washington, Seattle, WA 98104, USA; Department of Radiology, University of Washington, Seattle, WA 98104, USA.
⁷ Department of Neurological Surgery, University of Washington, Seattle, WA 98104, USA; Stroke & Applied Neurosciences Center, University of Washington, Seattle, WA 98104, USA; Department of Radiology, University of Washington, Seattle, WA 98104, USA; Department of Mechanical Engineering, University of Washington, Seattle, WA 98104, USA. Electronic address: mlevitt@uw.edu.

PMID: 36113244
DOI: 10.1016/j.jocn.2022.09.005

Abstract

Clinical significance of increased clopidogrel response measured by VerifyNow P2Y12 assay is unclear; management guidelines are lacking in the context of neuroendovascular intervention. Our objective was to assess whether increased clopidogrel response predicts complications from endovascular aneurysm treatment requiring dual antiplatelet therapy. A single-institution, 9-year retrospective study of patients undergoing endovascular treatments for ruptured and unruptured aneurysms requiring aspirin and clopidogrel was conducted. Patients were grouped according to preoperative platelet inhibition in response to clopidogrel measured by the VerifyNow P2Y12 assay (VNP; P2Y12 reactivity units, PRU). Demographic and clinical features were compared across groups. Hemorrhagic complication rates (intracranial, major extracranial, minor extracranial) and thromboembolic complications (in-stent stenosis, stroke/transient ischemic attack) were compared, controlling for potential confounders and multiple comparisons. Data were collected from 284 patients across 317 procedures. Pre-operative VNP assays identified 9 % Extreme Responders (PRU ≤ 15), 13 % Hyper-Responders (PRU 16-60), 62 % Therapeutic Responders (PRU 61-214), 16 % Hypo-Responders (PRU ≥ 215). Increased response to clopidogrel was associated with increased risk of any hemorrhagic complication (≤60 PRU vs > 60 PRU; 39 % vs 24 %, P = 0.050); all intracranial hemorrhages occurred in patients with PRU > 60. Thromboembolic complications were similar between therapeutic and subtherapeutic patients (<215 PRU vs ≥ 215 PRU; 15 % vs 16 %, P = 0.835). Increased preoperative clopidogrel response is associated with increased rate of extracranial hemorrhagic complications in endovascular aneurysm treatments. Hyper-responders (16-60 PRU) and Extreme Responders (≤15 PRU) were not associated with intracranial hemorrhagic or thrombotic complications. Hypo-responders who underwent adjustment of antiplatelet therapy and neurointerventions did not experience higher rates of complications.

Keywords: Clopidogrel; Intracranial aneurysm; Stent; VerifyNow.

MeSH terms

Aortic Aneurysm, Abdominal* / complications
Aortic Aneurysm, Abdominal* / surgery
Aspirin / adverse effects
Blood Vessel Prosthesis Implantation*
Clopidogrel / therapeutic use
Endovascular Procedures* / adverse effects
Humans
Intracranial Aneurysm* / complications
Intracranial Aneurysm* / drug therapy
Intracranial Aneurysm* / surgery
Platelet Aggregation Inhibitors / adverse effects
Retrospective Studies
Thromboembolism* / drug therapy
Thromboembolism* / etiology
Treatment Outcome

Substances

Platelet Aggregation Inhibitors
Clopidogrel
Aspirin