1155 Pharmacogenomics (2017) 12(18), 1155–1166 ISSN 1462-2416 part of Pharmacogenomics Research Article 10.2217/pgs-2017-0075 © 2017 Future Medicine Ltd Aim: Determine whether using CYP2C19 genotype to optimize antiplatelet therapy selection is cost effective over the initial 30 days and 1-year following percutaneous coronary intervention. Materials & methods: A cost–effectiveness analysis compared 30-day and 1-year outcomes and cost across three treatment strategies (universal clopidogrel, universal prasugrel, genotype-guided) in a hypothetical cohort. Results: Base-case scenario results at 30 days indicated that the incremental cost per major cardiovascular or bleeding event avoided for genotype-guided treatment was US$8525 and US$42,198 compared with universal clopidogrel and prasugrel, respectively. Probabilistic sensitivity analysis demonstrated that genotype-guided treatment was cost effective over 30 days and 1 year in 62 and 70% of simulations, respectively. Conclusion: Implementing a CYP2C19 genotype-guided approach to antiplatelet therapy could have a positive economic impact by preventing readmissions following percutaneous coronary intervention. First draft submitted: 1 May 2017; Accepted for publication: 1 June 2017; Published online: 26 July 2017 Keywords:฀ clopidogrel฀•฀cost–effectiveness฀•฀CYP2C19฀•฀genotype฀•฀pharmacogenomics฀ •฀prasugrel฀•฀readmission Approximately 600,000 percutaneous coro- nary interventions (PCI) with intracoro- nary stent placement are performed annu- ally in the USA in coronary artery disease (CAD) patients [1] . Dual antiplatelet therapy (DAPT) with aspirin and a P2Y 12 inhibitor is indicated following PCI for stable CAD or an acute coronary syndrome (ACS) event [2–4] . Platelet activation and aggregation play a central role in the pathophysiology of CAD, leading to increased risk of major adverse car- diovascular events (MACE) including death, myocardial infarction, ischemic stroke and stent thrombosis (ST). DAPT is indicated to reduce the risk of thrombotic MACE and ST events, but increases the risk for major and minor bleeding events [4] . Selection of the P2Y 12 inhibitor is based on clinical factors, such as indication for PCI and risk factors for bleeding, and economic considerations. In the USA, clopidogrel remains the most commonly prescribed P2Y 12 inhibitor [5,6] . Clopidogrel is a prodrug that requires bio- transformation by cytochrome P450 enzymes, specifically CYP2C19, to generate its active metabolite. Loss-of-function (LOF) polymor- phisms in CYP2C19 are common and confer a reduced capacity for clopidogrel bioactiva- tion and platelet inhibition [7] . Retrospective analyses of data from clinical trials and patient registries have demonstrated a higher risk for MACE and ST in clopidogrel-treated patients with one (intermediate metabolizer) or two (poor metabolizer) CYP2C19 LOF alleles after PCI compared with clopidogrel- treated patients without an LOF allele (nor- mal metabolizer) [8–10] . In contrast, CYP2C19 genotype does not alter the pharmacokinetics, antiplatelet effects or clinical response to pra- sugrel or ticagrelor [10,11] , which have shown CYP2C19 -guided antiplatelet therapy: a cost–effectiveness analysis of 30-day and 1-year outcomes following percutaneous coronary intervention Mrudula S Borse 1 , Olivia M Dong 2,3 , Melissa J Polasek 2 , Joel F Farley 1 , George A Stouffer 4,5 & Craig R Lee* ,2,3,4 1 Division฀of฀Pharmaceutical฀Outcomes฀ &฀Policy,฀UNC฀Eshelman฀School฀of฀ Pharmacy,฀University฀of฀North฀Carolina฀at฀ Chapel฀Hill,฀Chapel฀Hill,฀NC฀27599,฀USA 2 Division฀of฀Pharmacotherapy฀&฀ Experimental฀Therapeutics,฀UNC฀ Eshelman฀School฀of฀Pharmacy,฀University฀ of฀North฀Carolina฀at฀Chapel฀Hill,฀Chapel฀ Hill,฀NC฀27599,฀USA 3 UNC฀Center฀for฀Pharmacogenomics฀ &฀Individualized฀Therapy,฀University฀of฀ North฀Carolina฀at฀Chapel฀Hill,฀Chapel฀Hill,฀ NC฀27599,฀USA 4 UNC฀McAllister฀Heart฀Institute,฀ University฀of฀North฀Carolina฀at฀Chapel฀ Hill,฀Chapel฀Hill,฀NC฀27599,฀USA 5 Division฀of฀Cardiology,฀UNC฀School฀of฀ Medicine,฀University฀of฀North฀Carolina฀at฀ Chapel฀Hill,฀Chapel฀Hill,฀NC฀27599,฀USA *Author฀for฀correspondence:฀ Tel.:฀+1฀919฀843฀7673 Fax:฀+1฀919฀962฀0644 craig_lee@unc.edu For reprint orders, please contact: reprints@futuremedicine.com