Real-world evaluation of CYP2C19 guided antiplatelet therapy in patients undergoing intracranial aneurysm repair

Pharmacogenomics. 2024;25(12-13):503-513. doi: 10.1080/14622416.2024.2406213. Epub 2024 Oct 3.

Abstract

Aim: To evaluate the feasibility and impact of using CYP2C19 genotype to guide selection of antiplatelet therapy in patients undergoing intracranial aneurysm treatment with a flow diversion stent in a real-world clinical setting.Patients & methods: A single-center, retrospective, observational cohort study was conducted in 112 patients undergoing intracranial aneurysm repair with flow-diversion stenting from 2014 to 2021. Data were abstracted from health records. The frequency of clopidogrel or alternative therapy (ticagrelor or prasugrel) use was compared across CYP2C19 status (intermediate or poor metabolizer [IM/PM] vs. normal, rapid, or ultrarapid metabolizer [NM/RM/UM]).Results: In the study population, CYP2C19 genotype testing was performed on 110 (98.2%) patients; of these, 106 (97.2%) had results available prior to the stent procedure and 28 (25.5%) were IM/PMs. Alternative therapy was used more frequently in IM/PMs compared with NM/RM/UMs (57.1 vs. 8.5%, respectively, p < 0.0001). The frequency of thromboembolic events over 12 months did not significantly differ across clopidogrel-treated IM/PMs, clopidogrel-treated NM/RM/UMs and patients on alternative therapy (p = 0.352); although, event numbers were low.Conclusion: A pre-emptive 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.

Keywords: CYP2C19; antiplatelet therapy; clopidogrel; flow-diversion stenting; intracranial aneurysm; neurointerventional procedures; pharmacogenomics; stenting.

Plain language summary

This study offers new insight into how CYP2C19 genotyping can be used to more precisely select antiplatelet therapy in neurovascular disease patients undergoing intracranial aneurysm repair with flow diversion stenting.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Clopidogrel* / therapeutic use
  • Cytochrome P-450 CYP2C19* / genetics
  • Female
  • Genotype*
  • Humans
  • Intracranial Aneurysm* / drug therapy
  • Intracranial Aneurysm* / genetics
  • Intracranial Aneurysm* / surgery
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors* / administration & dosage
  • Platelet Aggregation Inhibitors* / therapeutic use
  • Prasugrel Hydrochloride / therapeutic use
  • Retrospective Studies
  • Stents*
  • Ticagrelor / therapeutic use

Substances

  • Cytochrome P-450 CYP2C19
  • Platelet Aggregation Inhibitors
  • CYP2C19 protein, human
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticagrelor