Consensus Statement on Genetic Testing for Guiding Post-PCI Antiplatelet Therapy

An international panel of experts has provided consensus statements on using platelet function/genetic testing for guiding antiplatelet treatment after percutaneous coronary intervention (PCI). The updated recommendations statement wereas published in the JAAC: Cardiovascular Interventions^.1

The availability of different P2Y12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled clinicians to consider individualized treatment regimens. In certain cases, it may be advisable to use platelet function testing (PFT) and genotyping to guide treatment. Further studies on dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor — the standard treatment for patients undergoing PCI — regarding de-escalation and escalation of P2Y12 inhibiting therapy are warranted to refine the existing treatment options.

While routine use of PFT or genetic testing is not recommended in PCI-treated patients, recent data called for a recommendation update that allows for selective PFT use of for DAPT de-escalation. As current guidelines don’t expand on when to consider or implement selective use of such assays in personalized treatment approaches, this international consensus group of experts convened to update 2 prior consensus papers on the topic.

General aspects of platelet function testing & PCI

Available assays for the ex-vivo assessment of on-treatment platelet reactivity to adenosine diphosphate (ADP) can be classified as near-patient-based or point-of-care assays (eg, Multiplate, VerifyNow, or thrombelastography) vs laboratory-based methods (eg vasodilator-stimulated phosphoprotein or light transmission aggregometry).

More studies are needed to define the therapeutic window for these treatments, and more importantly, how adjusting these treatments outside the window could impact bleeding risk and thrombotic complications. Optimal timing of PFT with relationship to PCI remains a topic of debate, and results depend upon a number of variables that change over time. Special considerations may be required for East Asian patients who have a different risk profile for ischemia and bleeding events compared with white patients.

PFT can be used in certain scenarios to test for antiplatelet treatment adherence, although results should be interpreted with caution, such as when high platelet reactivity (HPR) is present in clopidogrel-treated patients. Although the risk of stent thrombosis has significantly declined, it can be life-threatening, and PFT can be useful when seeking causative factors.

PFT for risk prediction and treatment guidance in stable coronary artery disease (CAD)CAD patients

For more than a decade, findings from observational studies have supported P2Y12-directed PFT for cardiovascular risk prediction after elective PCI, and these data have established measurements of PFT as a cardiovascular biomarker in patients with coronary artery disease (CAD).

Escalation strategies

Limited evidence from randomized trials is available supporting using PFT for routine treatment guidance with the goal of escalating P2Y12 inhibitor treatment (ie switching from clopidogrel to prasugrel or ticagrelor) in elective PCI patients exhibiting HPR on clopidogrel, and all major dials with the guided DAPT approach failed to meet primary endpoint tables.

Despite promising data from a few smaller randomized studies and a respective meta-analysis and other non-randomized data on PFT in stable CAD patients, the available evidence is against routine use of PFT for treatment escalation in HPR patients on clopidogrel. Nevertheless, this expert group agrees it is reasonable to consider selective, optional use of PFT to guide P2Y12 escalation in specific scenarios with patients not at excessive risk of bleeding where adequate platelet inhibition is crucial (eg, left main stenting, last patent vessel PCI, complex lesions, 2-stent bifurcation treatment, prior stent thrombosis).

De-escalation strategies

Clinicians may consider stopping one of the antiplatelet drugs (aspirin or clopidogrel) in certain scenarios with patients on DAPT, such as in cases where bleeding is a concern, eg patients who also require treatment with oral anticoagulants. Data on PFT cutoff values in these scenarios is limited, and values that would best determine risk may indeed be different within this cohort.

Data in utilizing PFT for stable patients in such a setting to screen for drug responsiveness when choosing which drug to stop is limited; nevertheless, this expert group agrees it may be reasonable to consider PFT use in specific clinical settings (socio-economic indications, high bleeding risk, bleeding events). For TEG platelet mapping, the cut-off values to determine HPR status is 47 mm. For vasodilator-stimulated phosphoprotein, the cut-off for HPR is 50% PRI. For Mulitiplate Analyzer, HPR cut-off is 46 U. For VerifyNow P2Y12, HPR cut-off is 208 PRU.

PFT for risk prediction and treatment guidance in acute coronary syndrome (ACS) patients

Observational data does lend some support to using P2Y12-directed PFT for cardiovascular risk prediction after ACS-PCI. Current guidelines for these patients strongly recommend the use of prasugrel or ticagrelor over clopidogrel in the absence of contraindications. However, a presumed high risk of bleeding or socio-economic issues may favor clopidogrel use in some cases.