Role of genetic testing in patients undergoing percutaneous coronary intervention

Abstract

Introduction Variability in individual response profiles to antiplatelet therapy, in particular clopidogrel, is a well-established phenomenon. Genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key determinant in clopidogrel metabolism, have been associated with clopidogrel response profiles. Moreover, the presence of a CYP2C19 loss-of-function allele is associated with an increased risk of atherothrombotic events among clopidogrel-treated patients undergoing percutaneous coronary interventions (PCI), prompting studies evaluating the use of genetic tests to identify patients who may be potential candidates for alternative platelet P2Y12 receptor inhibiting therapies (prasugrel or ticagrelor). Areas covered The present manuscript provides an overview of genetic factors associated with response profiles to platelet P2Y12 receptor inhibitors and their clinical implications, as well as the most recent developments and future considerations on the role of genetic testing in patients undergoing PCI. Expert Commentary The availability of more user-friendly genetic tests has contributed towards the development of many ongoing clinical trials and personalized medicine programs for patients undergoing PCI. Results of pilot investigations have shown promising results, which however need to be confirmed in larger-scale studies to support the routine use of genetic testing as a strategy to personalize antiplatelet therapy and improve clinical outcomes.

CYP2C19 pharmacogenetics versus standard of care dosing for selecting antiplatelet therapy in patients with coronary artery disease: A meta‐analysis of randomized clinical trials

“…P2Y 12 receptor inhibitors are an important part of the management of patients undergoing coronary stenting, especially if they have acute coronary syndromes (ACS). Although ticagrelor and prasugrel are superior in preventing ischemic events, clopidogrel is the most utilized P2Y 12 receptor antagonist worldwide.…”

International Expert Consensus on Switching Platelet P2Y 12 Receptor–Inhibiting Therapies

“…53,[75][76][77] There are limited data assessing the clinical impact of escalation and de-escalation of antiplatelet therapy on the basis of the results of genetic testing, which is currently being evaluated in several randomized trials, including the use of rapid genetic testing. 78 Overall, there is a paucity of studies assessing the pharmacodynamic effects associated with de-escalation to clopidogrel therapy that have consistently shown an increase in platelet reactivity and HPR rates, with some reporting lower bleeding events (Table IV in the onlineonly Data Supplement). 19,49,51,52,56,79,80 However, these findings, as well as the absence of increased thrombotic events despite a higher rate of patients developing HPR, should be interpreted with caution because none of these studies were powered for clinical outcomes.…”

Personalized antiplatelet therapy in patients with coronary artery disease undergoing percutaneous coronary intervention: A network meta‐analysis of randomized clinical trials

“…The Food and Drug Administration has issued a warning label because of the variation of clopidogrel responsiveness in patients with loss‐of‐function CYP2C19 alleles . Therefore, the “one size fits all” strategy for clopidogrel usage in PCI‐treated patients with coronary artery disease has shifted to more individualized therapy strategies.…”

“…Current percutaneous coronary intervention (PCI) guidelines recommend the use of potent P2Y 12 receptor inhibitors (ticagrelor or prasugrel) in patients with acute coronary syndrome (ACS) treated with dual antiplatelet therapy after coronary stent implantation (Class IIa) . Although potent P2Y 12 receptor inhibitors are associated with a greater reduction of thrombotic events, the risk of bleeding is higher than with the less potent P2Y 12 antagonist clopidogrel . Nevertheless, clopidogrel, a prodrug needing hepatic metabolism, has shown a broad interindividual response variability which could lead to high on‐treatment platelet reactivity (HTPR) and, thus, inadequate platelet inhibition response and increased risk of ischemic events .…”

“…Although potent P2Y 12 receptor inhibitors are associated with a greater reduction of thrombotic events, the risk of bleeding is higher than with the less potent P2Y 12 antagonist clopidogrel . Nevertheless, clopidogrel, a prodrug needing hepatic metabolism, has shown a broad interindividual response variability which could lead to high on‐treatment platelet reactivity (HTPR) and, thus, inadequate platelet inhibition response and increased risk of ischemic events . Therefore, personalized antiplatelet therapy with particular consideration of clopidogrel pharmacogenetic and pharmacodynamic characteristics has gained much attention.…”