Scientific Poster Session I - Original Research

Original Research
  Saturday, November 11, 2023
  11:30 AM–01:00 PM

Abstract

Introduction: Clopidogrel, a prodrug metabolized by CYP2C19, is standard of care to prevent thromboembolic complications after intracranial aneurysm repair with flow diversion stenting (FDS). While clinical implementation of CYP2C19 genotype-guided antiplatelet therapy selection is feasible and improves clinical outcomes in patients undergoing percutaneous coronary intervention, the feasibility and utility of this precision medicine strategy in neuro-interventional procedures remains unclear.

Research Question or Hypothesis: Is use of CYP2C19 genotype to guide antiplatelet therapy selection feasible and associated with improved outcomes in patients undergoing intracranial aneurysm repair?

Study Design: Single-center observational cohort study

Methods: Patients undergoing intracranial aneurysm repair with FDS from 2014-2021 were included (n=112). Demographics, clinical characteristics, CYP2C19 metabolizer phenotype, medications, and outcomes were abstracted from health records. The frequency of clopidogrel or alternative therapy (ticagrelor, prasugrel) use was compared across CYP2C19 status (intermediate or poor metabolizer [IM/PM] vs. normal, rapid, or ultrarapid metabolizer [NM/RM/UM]) using a ?² test or Fisher’s exact test. The frequency of thromboembolic (ischemic stroke or transient ischemic attack) and major bleeding outcomes over 12 months was compared across CYP2C19-antiplatelet therapy groups.

Results: The population included 25.0% Black and 81.0% female patients; 7.1% presented with acute subarachnoid hemorrhage. CYP2C19 genotype testing was performed on 110 (98.2%) patients; of these, 106 (97.2%) had results available prior to FDS and 28 (25.5%) were IM/PMs. Alternative therapy was used more frequently in IM/PMs compared to NM/RM/UMs (57.1% vs. 8.5%, respectively, p<0.0001). Though statistically non-significant (p=0.352), thromboembolic events occurred more frequently in clopidogrel-treated IM/PMs (3 events, 25.0%) compared to clopidogrel-treated NM/RM/UMs (7, 9.3%) and patients on alternative therapy (3, 13.0%). Major bleeding did not differ across groups (p=0.942).

Conclusion: A preemptive CYP2C19 genotyping strategy to guide antiplatelet therapy selection in intracranial aneurysm repair patients is feasible in a real-world clinical setting. Larger studies are needed to assess the impact on clinical outcomes.

Presenting Author

Layna Fox PharmD Candidate
UNC Eshelman School of Pharmacy

Authors

Craig Lee PharmD, PhD, FCCP
UNC Eshelman School of Pharmacy

Anh Nguyen PharmD
UNC Eshelman School of Pharmacy

Nathan Quig MD
Department of Neurosurgery

Kayla Tunehag MSPH, PharmD
UNC Eshelman School of Pharmacy

Samuel Reed MD
Department of Neurosurgery

Darshan Shastri MD
Department of Neurosurgery

Sten Solander MD
George A. Stouffer MD
UNC School of Medicine