Real-world evaluation of <i>CYP2C19</i> guided antiplatelet therapy in patients undergoing intracranial aneurysm repair
Creators: name: Fox, Layna P
name: Tunehag, Kayla R
name: Nguyen, Anh
name: Reed, Samuel
name: Shastri, Darshan
name: Quig, Nathan
name: Stouffer, George A
name: Solander, Sten
name: Lee, Craig R
Publisher: name: Taylor & Francis
Year: 2024
Subjects: Space Science
Medicine
Cancer
Hematology

description: <b>Aim:</b> To evaluate the feasibility and impact of using <i>CYP2C19</i> genotype to guide selection of antiplatelet therapy in patients undergoing intracranial aneurysm treatment with a flow diversion stent in a real-world clinical setting. <b>Patients &amp; methods:</b> 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]). <b>Results:</b> In the study population, <i>CYP2C19</i> 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, <i>p</i> &lt; 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 (<i>p</i> = 0.352); although, event numbers were low. <b>Conclusion:</b> A pre-emptive <i>CYP2C19</i> 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. This study offers new insight into how <i>CYP2C19</i> genotyping can be used to more precisely select antiplatelet therapy in neurovascular disease patients undergoing intracranial aneurysm repair with flow diversion stenting. Clopidogrel, a prodrug metabolized by CYP2C19, is indicated to prevent thromboembolic complications after neurointerventional procedures. While clinical implementation of <i>CYP2C19</i> genotype-guided antiplatelet therapy selection improves clinical outcomes in patients undergoing percutaneous coronary intervention, the feasibility and utility of this precision medicine strategy in patients undergoing neurointerventional procedures such as intracranial aneurysm repair remains unclear. This single-center retrospective study evaluated the feasibility of using <i>CYP2C19</i> genotype to guide selection of antiplatelet therapy in 112 patients undergoing intracranial aneurysm treatment with a flow diversion stent in a real-world clinical setting. At our institution, a high rate of pre-emptive <i>CYP2C19</i> testing prior to flow diversion stenting was observed. In accordance with Clinical Pharmacogenetics Implementation Consortium guideline recommendations, prescribers were significantly more likely to select alternative therapy (such as ticagrelor) compared with standard therapy (clopidogrel) in patients with a <i>CYP2C19</i> no function allele. The number of thromboembolic and clinically significant bleeding events over 12 months were low and did not significantly differ across CYP2C19-antiplatelet therapy groups. Collectively, these results demonstrate the feasibility of using genotype results to guide antiplatelet therapy selection in patients undergoing intracranial aneurysm repair at an institution that previously implemented <i>CYP2C19</i> testing in patients undergoing a percutaneous coronary intervention procedure. These results can inform future multicenter investigations evaluating the effectiveness and safety of <i>CYP2C19</i> genotype guided antiplatelet selection to prevent thromboembolic complications in the setting of neurointerventional procedures.