Genetic testing in patients undergoing percutaneous coronary intervention: rationale, evidence and practical recommendations

ABSTRACT

Introduction

Clopidogrel is the most frequently utilized P2Y₁₂ inhibitor and is characterized by broad interindividual response variability resulting in impaired platelet inhibition and increased risk of thrombotic complications in a considerable number of patients. The potent P2Y₁₂ inhibitors, prasugrel and ticagrelor, can overcome this limitation but at the expense of an increased risk of bleeding. Genetic variations of the cytochrome P450 (CYP) 2 C19 enzyme, a key determinant in clopidogrel metabolism, have been strongly associated with clopidogrel response profiles prompting investigations of genetic-guided selection of antiplatelet therapy.

Areas covered

The present manuscript focuses on the rationale for the use of genetic testing to guide the selection of platelet P2Y₁₂ inhibitors among patients undergoing percutaneous coronary intervention (PCI). Moreover, a comprehensive appraisal of the available evidence and practical recommendations is provided.

Expert Commentary

Implementation of genetic testing as a strategy to guide the selection of therapy can result in escalation (i.e. switching to prasugrel or ticagrelor) or de-escalation (i.e. switching to clopidogrel) of P2Y₁₂ inhibiting therapy. Most recent investigations support the clinical benefit of a genetic guided selection of antiplatelet therapy in patients undergo PCI. Integrating the results of genetic testing with clinical and procedural variables represents a promising strategy for a precision medicine approach for the selection of antiplatelet therapy among patients undergoing PCI.

KEYWORDS:

• Genetics
• antiplatelet therapy
• bleeding
• thrombosis
• percutaneous coronary intervention
• p2y₁₂ inhibitors

Article highlights

• Approximately 30% of patients treated with clopidogrel persist with high platelet reactivity, a marker of thrombotic risk in patients undergoing percutaneous coronary intervention (PCI). Although the use of potent P2Y₁₂ inhibitors (i.e. prasugrel and ticagrelor) can overcome this limitation, this occurs at the expenses of an increased risk of bleeding.

• Genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key determinant in clopidogrel metabolism, have been strongly associated with clopidogrel response profiles prompting investigations of genetic-guided selection of antiplatelet therapy.

• Implementation of genetic testing as a strategy to guide the selection of therapy can result into escalation (i.e. use of prasugrel or ticagrelor) or de-escalation (i.e. use of clopidogrel) of P2Y₁₂ inhibiting therapy with the goal of optimizing safety and efficacy outcomes.

•Integrating the results of genetic testing with clinical and procedural variables represents a promising strategy for a precision medicine approach for the selection of antiplatelet therapy among patients undergoing PCI.

Declaration of interest

F. Franchi declares having received consulting fees or honoraria from AstraZeneca, Bayer and Sanofi. F. Rollini declares having received honoraria from Chiesi. D.Capodanno declares having received consulting and speaker’s fee from Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Menarini outside the present work. F.Crea declares receiving consulting and speaker’s fees from Biotronic, Amgen, Astra Zeneca, Servier, Menarini, BMS, outside the present work. D.J. Angiolillo declares having received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company and has received payments for participation in review activities from CeloNova and St Jude Medical, outside the present work. D.J. Angiolillo also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions and Scott R. MacKenzie Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by NIH/NHLBI R01 HL149752 (LHC, DJA) and NIH/NCATS UL1 TR001427 (LHC). M.Galli is supported by a grant from Fondazione Enrico Ed Enrica Sovena (Rome, Italy).