Key result
CYP2C19 genetic-guided P2Y12 inhibitor selection allows tailored escalation or de-escalation after PCI to balance ischemic protection and bleeding risk.
Why the study?
Clopidogrel has broad interindividual response variability linked to CYP2C19 genetic variations, while potent alternatives increase bleeding risk, prompting the need to appraise genetic testing to guide P2Y12 inhibitor selection.
Does CYP2C19 genetic-guided selection of oral P2Y12 inhibitors improve the balance of ischemic and bleeding outcomes compared to conventional unguided therapy in patients undergoing percutaneous coronary intervention?
Does CYP2C19 genetic-guided selection of oral P2Y12 inhibitors improve the balance of ischemic and bleeding outcomes compared to conventional unguided therapy in patients undergoing percutaneous coronary intervention?
Answers are grounded in this paper and cite their sources.
Integrating rapid CYP2C19 genetic testing with clinical and procedural variables enables personalized P2Y12 inhibitor escalation or de-escalation to optimize ischemic protection while minimizing bleeding risk in PCI patients.
Introduction Clopidogrel is the most frequently utilized P2Y12 inhibitor and is characterized by broad interindividual response variability resulting in impaired platelet inhibition and increased risk of thrombotic complications in a considerable number of patients. The potent P2Y12 inhibitors, prasugrel and ticagrelor, can overcome this limitation but at the expense of an increased risk of bleeding. Genetic variations of the cytochrome P450 (CYP) 2 C19 enzyme, a key determinant in clopidogrel metabolism, have been strongly associated with clopidogrel response profiles prompting investigations of genetic-guided selection of antiplatelet therapy.Areas covered The present manuscript focuses on the rationale for the use of genetic testing to guide the selection of platelet P2Y12 inhibitors among patients undergoing percutaneous coronary intervention (PCI). Moreover, a comprehensive appraisal of the available evidence and practical recommendations is provided.Expert Commentary Implementation of genetic testing as a strategy to guide the selection of therapy can result in escalation (i.e. switching to prasugrel or ticagrelor) or de-escalation (i.e. switching to clopidogrel) of P2Y12 inhibiting therapy. Most recent investigations support the clinical benefit of a genetic guided selection of antiplatelet therapy in patients undergo PCI. Integrating the results of genetic testing with clinical and procedural variables represents a promising strategy for a precision medicine approach for the selection of antiplatelet therapy among patients undergoing PCI.
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Galli et al. (2021) conducted a review in Coronary artery disease (acute and chronic coronary syndromes) undergoing percutaneous coronary intervention (PCI). CYP2C19 genetic testing to guide oral P2Y12 inhibitor selection (escalation or de-escalation) vs. Conventional unguided P2Y12 inhibitor selection (clopidogrel, prasugrel, or ticagrelor) was evaluated. CYP2C19 genetic-guided P2Y12 inhibitor selection allows tailored escalation or de-escalation after PCI to balance ischemic protection and bleeding risk.
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