2024 International Consensus on Platelet Function and Genetic Testing in PCI: Key Highlights

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is vital for preventing thrombotic events after PCI but increases bleeding risk in some patients.

Oral P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) differ in pharmacodynamics, prompting advocacy for platelet function and genetic testing to personalize treatment.

High residual platelet reactivity occurs in up to one-third of clopidogrel users, raising thrombotic risk, while prasugrel and ticagrelor increase bleeding without always reducing ischemic risks.

Clopidogrel metabolism relies on the hepatic CYP2C19 system, where genetic variations affect drug activation; prasugrel and ticagrelor are unaffected by this pathway.

Distinct CYP2C19 metabolizer phenotypes include ultrarapid, rapid, normal, intermediate, and poor metabolizers.

The prevalence of poor metabolizers varies by ancestry: 2-4% in Europeans/Africans and 10-15% in East Asians, who also show the "East Asian paradox" of fewer ischemic events and more bleeding.

Two testing modalities—platelet function testing and genetic testing—aid in guided P2Y12 inhibitor therapy selection.

Point-of-care platelet function testing is convenient but shows variability and timing uncertainties relative to PCI and clopidogrel use.

Testing helps identify patients at high thrombotic risk and guides escalation or de-escalation strategies with ticagrelor/prasugrel or switching to clopidogrel.

Platelet function/genetic testing is discouraged in low-complexity PCI cases due to low ischemic event rates.

Testing may guide escalation to prasugrel/ticagrelor in high-risk chronic coronary syndrome patients with complex procedures or recurrent events.

Testing is recommended in acute coronary syndrome patients at elevated ischemic and bleeding risks for guided de-escalation from prasugrel/ticagrelor to clopidogrel.

Testing is valuable for antiplatelet monotherapy with clopidogrel, especially early post-PCI in high-risk patients or those with recurrent ischemic events.

Key Points:

• DAPT effectiveness and bleeding risks require careful patient selection.
• Testing modalities provide tools for personalized antiplatelet therapy.
• Ethnic variations impact clopidogrel response and event rates.
• Guided strategies optimize outcomes in high-risk and complex cases.