title: CYP2C19 LOF and GOF-Guided Antiplatelet Therapy in Patients with Acute Coronary Syndrome: A Cost-Effectiveness Analysis.
abstract: OBJECTIVE
  This study aimed to examine the cost-effectiveness of CYP2C19 loss-of-function and gain-of-function allele guided (LOF/GOF-guided) antiplatelet therapy in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).
  
  
  METHODS
  A life-long decision-analytic model was designed to simulate outcomes of three strategies: universal clopidogrel (75 mg daily), universal alternative P2Y12inhibitor (prasugrel 10 mg daily or ticagrelor 90 mg twice daily), and LOF/GOF-guided therapy (LOF/GOF allele carriers receiving alternative P2Y12inhibitor, wild-type patients receiving clopidogrel). Model outcomes included clinical event rates, quality-adjusted life-years (QALYs) gained and direct medical costs from perspective of US healthcare provider.
  
  
  RESULTS
  Base-case analysis found nonfatal myocardial infarction (5.62%) and stent thrombosis (1.2%) to be the lowest in universal alternative P2Y12inhibitor arm, whereas nonfatal stroke (0.72%), cardiovascular death (2.42%), and major bleeding (2.73%) were lowest in LOF/GOF-guided group. LOF/GOF-guided arm gained the highest QALYs (7.5301 QALYs) at lowest life-long cost (USD 76,450). One-way sensitivity analysis showed base-case results were subject to the hazard ratio of cardiovascular death in carriers versus non-carriers of LOF allele and hazard ratio of cardiovascular death in non-carriers of LOF allele versus general patients. In probabilistic sensitivity analysis of 10,000 Monte Carlo simulations, LOF/GOF-guided therapy, universal alternative P2Y12inhibitor, and universal clopidogrel were the preferred strategy (willingness-to-pay threshold = 50,000 USD/QALY) in 99.07%, 0.04%, and 0.89% of time, respectively.
  
  
  CONCLUSIONS
  Using both CYP2C19 GOF and LOF alleles to select antiplatelet therapy appears to be the preferred antiplatelet strategy over universal clopidogrel and universal alternative P2Y12inhibitor therapy for ACS patients with PCI.
authors.affiliation: School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N. T, Hong Kong, China.
authors.forename: Minghuan
authors.initials: M
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N. T, Hong Kong, China. joyceyou@cuhk.edu.hk.
authors.forename: Joyce H S
authors.initials: JH
authors.lastname: You
mesh_terms: D054058:Acute Coronary Syndrome / Q000191:economics* / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D000241:Adenosine / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D000077144:Clopidogrel; D003198:Computer Simulation; D003328:Coronary Thrombosis / Q000191:economics / Q000209:etiology; D003362:Cost-Benefit Analysis; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism; D003661:Decision Support Techniques; D016527:Drug Costs; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced / Q000191:economics; D006801:Humans; D018803:Models, Economic; D009010:Monte Carlo Method; D009203:Myocardial Infarction / Q000191:economics / Q000209:etiology; D018579:Patient Selection; D062645:Percutaneous Coronary Intervention / Q000191:economics*; D000071185:Pharmacogenomic Testing / Q000191:economics*; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000191:economics* / Q000378:metabolism / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride / Q000191:economics / Q000627:therapeutic use; D011237:Predictive Value of Tests; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000191:economics* / Q000378:metabolism / Q000627:therapeutic use*; D019057:Quality-Adjusted Life Years; D012307:Risk Factors; D020521:Stroke / Q000191:economics / Q000209:etiology; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Acute coronary syndrome; CYP2C19 genotype; Clopidogrel; Cost-effectiveness; Prasugrel; Ticagrelor