Consensus on Platelet Function and Genetic Testing in PCI: Key Points
The following are key points to remember from a 2024 updated international consensus statement on platelet function and genetic testing in percutaneous coronary intervention (PCI):
- Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is essential for the prevention of thrombotic events after PCI. However, DAPT is associated with increased bleeding, which can outweigh the benefits in select patients.
- Oral P2Y12 inhibitors clopidogrel, prasugrel, and ticagrelor each have different pharmacodynamic profiles that affect their clinical effectiveness and safety. As such, many experts have advocated for platelet function and genetic testing to individualize treatment regimens.
- Up to one-third of patients treated with clopidogrel and a small minority of those treated with prasugrel or ticagrelor demonstrate high residual platelet reactivity that result in an increased thrombotic risk. On the other hand, both prasugrel and ticagrelor are associated with increased bleeding risk and may not reduce ischemic event risk when compared to patients who appropriately respond to clopidogrel.
- Clopidogrel is a prodrug that requires a two-step oxidation process by the hepatic CYP2C19 system to generate an active metabolite. The gene for CYP2C19 can experience either a gain-of-functionor loss-of-function variation that can lead to reduced or increased active drug levels, respectively. This gene is not involved in prasugrel or ticagrelor metabolism.
- The loss- and gain-of function levels lead to five distinct phenotypes: ultrarapid metabolizers, rapid metabolizers, normal metabolizers, intermediate metabolizers, and poor metabolizers.
- The prevalence of poor and intermediate metabolizers are 2-4% and 25-35% among European and African ancestry populations, respectively. The prevalence of poor and intermediate metabolizers are 10-15% and 40-50% among East Asian ancestry populations, respectively. However, East Asian populations have a lower rate of ischemic events and higher rate of bleeding events when treated with clopidogrel, known as the “East Asian paradox.”
- Two modalities are available to enable guided selection of P2Y12 inhibitor therapy: platelet function testing and genetic testing. Platelet function testing directly measures platelet reactivity and response to specific antiplatelet agents. Genetic testing identifies specific CYP2C19 alleles that are associated with clopidogrel response.
- While point-of-care platelet function testing is convenient, there is considerable inter-assay variability, and the results may not be interchangeable. Furthermore, there is uncertainty on the optimal timing of testing related to PCI and the need to already be taking clopidogrel before performing testing.
- Platelet function testing or genetic testing can be used to identify patients at high thrombotic risk, the potential role of utilizing ticagrelor/prasugrel in patients who are poor clopidogrel responders, and the potential implications of changing from ticagrelor/prasugrel to clopidogrel.
- The experts recommend against using platelet function testing or genetic testing in patients undergoing PCI of low complexity given the low rate of ischemic events.
- The experts recommend considering the use of platelet function testing or genetic testing to guide escalation strategies to prasugrel/ticagrelor in patients with chronic coronary syndromes at high thrombotic risk based on procedural complexity and clinical characteristics (e.g., a history of recurrent coronary events).
- The experts recommend considering the use of platelet function testing or genetic testing in patients with acute coronary syndrome at an increased risk of bleeding and ischemic events (but not a prohibitive risk of bleeding) in whom a strategy of guided de-escalation of switching from prasugrel/ticagrelor to clopidogrel is being considered.
- The experts recommend that a prominent role of platelet function testing or genetic testing may be in patients being considered for antiplatelet monotherapy with clopidogrel, especially if early after PCI (e.g., 1-3 months) and in patients at high clinical and/or procedural ischemic risk or with a history of recurrent ischemic events.
