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Published on: March 15, 2022
CYP2C19 Genotype-Guided Antiplatelet Therapy and Clinical Outcomes in Patients Undergoing a Neurointerventional
Kayla R Tunehag1, Ashton F Pearce1, Layna P Fox1
1Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Insights
CYP2C19 genotype testing can guide antiplatelet therapy selection for stroke prevention. Patients with specific CYP2C19 gene variants may have worse outcomes with clopidogrel, suggesting a need for genotype-guided treatment strategies.
Area of Science:
- Neuroscience
- Pharmacogenomics
- Cardiovascular Medicine
Background:
- Dual antiplatelet therapy (P2Y12 inhibitor and aspirin) is standard for neurovascular conditions.
- Clopidogrel is a common P2Y12 inhibitor, but its efficacy is reduced in individuals with CYP2C19 no-function alleles.
- CYP2C19 genotype affects clopidogrel's active metabolite formation, impacting platelet inhibition.
Purpose of the Study:
- To review evidence and guidelines for CYP2C19 genotype-guided antiplatelet therapy in neurovascular disease.
- To evaluate clinical outcomes related to CYP2C19 genotype and clopidogrel in neurointerventional procedures.
- To identify knowledge gaps and future research directions in this field.
Main Methods:
- Literature review and synthesis of existing evidence.
- Analysis of guideline recommendations for CYP2C19 genotype-guided therapy.
- Evaluation of clinical outcomes data from neurointerventional procedures.
Main Results:
- CYP2C19 no-function alleles are linked to poorer outcomes in clopidogrel-treated neurovascular patients.
- Genotype-guided therapy has shown improved outcomes in cardiovascular percutaneous coronary intervention.
- Evidence for genotype-guided therapy in neurointerventional procedures is still developing.
Conclusions:
- CYP2C19 genotype significantly influences clopidogrel response in neurovascular patients.
- Implementing genotype-guided antiplatelet therapy may optimize treatment and reduce adverse events.
- Further research is needed to clarify the utility and impact of genotype-guided strategies in neurointerventional settings.
Abstract:
In neurovascular settings, including treatment and prevention of ischemic stroke and prevention of thromboembolic complications after percutaneous neurointerventional procedures, dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is the standard of care. Clopidogrel remains the most commonly prescribed P2Y12 inhibitor for neurovascular indications. However, patients carrying CYP2C19 no-function alleles have diminished capacity for inhibition of platelet reactivity due to reduced formation of clopidogrel's active metabolite. In patients with cardiovascular disease undergoing a percutaneous coronary intervention, CYP2C19 no-function allele carriers treated with clopidogrel experience a higher risk of major adverse cardiovascular outcomes, and multiple large prospective outcomes studies have shown an improvement in clinical outcomes when antiplatelet therapy selection was guided by CYP2C19 genotype. Similarly, accumulating evidence has associated CYP2C19 no-function alleles with poor clinical outcomes in clopidogrel-treated patients in neurovascular settings. However, the utility of implementing a genotype-guided antiplatelet therapy selection strategy in the setting of neurovascular disease and the clinical outcomes evidence in neurointerventional procedures remains unclear. In this review, we will (1) summarize existing evidence and guideline recommendations related to CYP2C19 genotype-guided antiplatelet therapy in the setting of neurovascular disease, (2) evaluate and synthesize the existing evidence on the relationship of clinical outcomes to CYP2C19 genotype and clopidogrel treatment in patients undergoing a percutaneous neurointerventional procedure, and (3) identify knowledge gaps and discuss future research directions.
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