Personalized antiplatelet therapy: state of the art

Area of Science:

• Cardiology
• Pharmacogenomics
• Thrombosis Research

Background:

• Platelet activation and aggregation are central to myocardial infarction and stent thrombosis.
• Dual antiplatelet therapy is effective, but clopidogrel response varies, with ~33% of patients showing high on-treatment platelet reactivity (HPR).
• Current practice often employs a non-selective approach to antiplatelet therapy, lacking objective assessment of P2Y12 receptor interaction intensity.

Purpose of the Study:

• To review the evidence linking high on-treatment platelet reactivity (HPR) and CYP2C19 loss-of-function (LoF) carriage to clinical outcomes in high-risk patients.
• To discuss the rationale for personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI).

Main Methods:

• Review of pharmacodynamic studies and clinical outcome data related to clopidogrel therapy.
• Analysis of the association between HPR, CYP2C19 genotype, and patient outcomes post-PCI.
• Evaluation of current clinical guidelines and recommendations regarding antiplatelet therapy assessment.

Main Results:

• High on-treatment platelet reactivity (HPR) and CYP2C19 loss-of-function (LoF) carriage are linked to adverse clinical outcomes in high-risk patients treated with clopidogrel after PCI.
• A class IIb recommendation exists for genotyping or phenotyping in high-risk PCI patients if treatment adjustment is considered.
• While large-scale randomized trials are pending, current evidence suggests potential benefits of personalized antiplatelet strategies.

Conclusions:

• Assessing platelet function and performing genotyping in high-risk clopidogrel-treated patients may be reasonable.
• Selective treatment with more potent P2Y12 receptor antagonists could be considered for patients identified with HPR or specific genetic profiles.
• Personalized antiplatelet therapy holds promise for improving outcomes in high-risk cardiovascular patients.