Genotype-Guided Antiplatelet Therapy: JACC Review Topic of the Week (JACC September 2024-2)-Article: Genotype-Guided Antiplatelet Therapy JACC Review Topic of the Week

Article: Genotype-Guided Antiplatelet Therapy JACC Review Topic of the Week

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The article discusses genotype-guided antiplatelet therapy, which personalizes drug treatments based on genetic variations to improve efficacy and safety in patients. Traditional antiplatelet therapies, such as dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors, are not universally effective due to individual genetic differences. These differences, particularly in the CYP2C19 gene, affect drug metabolism and can lead to either increased bleeding or insufficient prevention of ischemic events.<br /><br />Genotype-guided strategies can be classified into two main approaches: de-escalation and escalation. In de-escalation, potent inhibitors like ticagrelor or prasugrel are switched to clopidogrel in normal metabolizers to reduce bleeding risk. Conversely, escalation involves switching clopidogrel to more potent inhibitors in patients with reduced metabolic function (poor metabolizers) to decrease the risk of ischemic events.<br /><br />Despite promising results from clinical trials demonstrating the benefits of such tailored therapies, genotype-guided treatment is not widely implemented in clinical settings. Barriers include the lack of routine genetic testing, cost implications, and limited insurance coverage for such genetic tests and newer antiplatelet agents.<br /><br />Clinical guidelines on the use of genotype-guided therapy vary. Some guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group, recommend alternative P2Y12 inhibitors for patients identified as poor or intermediate metabolizers. Other guidelines, like those from the American College of Cardiology/American Heart Association (ACC/AHA), suggest considering genotyping in high-risk patients undergoing PCI but lack strong recommendations.<br /><br />Ongoing research and technological advancements may facilitate broader adoption of genotype-guided antiplatelet therapy. Future studies aim to provide more definitive evidence and explore cost-effective strategies for implementing these personalized treatment approaches, potentially making them part of the standard care for patients undergoing PCI.

Keywords

genotype-guided therapy

antiplatelet treatment

CYP2C19 gene

dual antiplatelet therapy

ticagrelor

prasugrel

clopidogrel

personalized medicine

pharmacogenetics

PCI