CYP2C19 LOF and GOF-Guided Antiplatelet Therapy in Patients with Acute Coronary Syndrome: A Cost-Effectiveness Analysis

Cardiovasc Drugs Ther. 2017 Feb;31(1):39-49. doi: 10.1007/s10557-016-6705-y.

Abstract

Purpose: 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 P2Y12 inhibitor (prasugrel 10 mg daily or ticagrelor 90 mg twice daily), and LOF/GOF-guided therapy (LOF/GOF allele carriers receiving alternative P2Y12 inhibitor, 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 P2Y12 inhibitor 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 P2Y12 inhibitor, 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 P2Y12 inhibitor therapy for ACS patients with PCI.

Keywords: Acute coronary syndrome; CYP2C19 genotype; Clopidogrel; Cost-effectiveness; Prasugrel; Ticagrelor.

MeSH terms

  • Acute Coronary Syndrome / economics*
  • Acute Coronary Syndrome / enzymology
  • Acute Coronary Syndrome / genetics
  • Acute Coronary Syndrome / therapy*
  • Adenosine / analogs & derivatives
  • Adenosine / economics
  • Adenosine / therapeutic use
  • Clopidogrel
  • Computer Simulation
  • Coronary Thrombosis / economics
  • Coronary Thrombosis / etiology
  • Cost-Benefit Analysis
  • Cytochrome P-450 CYP2C19 / genetics*
  • Cytochrome P-450 CYP2C19 / metabolism
  • Decision Support Techniques
  • Drug Costs*
  • Genotype
  • Hemorrhage / chemically induced
  • Hemorrhage / economics
  • Humans
  • Models, Economic
  • Monte Carlo Method
  • Myocardial Infarction / economics
  • Myocardial Infarction / etiology
  • Patient Selection
  • Percutaneous Coronary Intervention / economics*
  • Pharmacogenomic Testing / economics*
  • Pharmacogenomic Variants*
  • Phenotype
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / economics*
  • Platelet Aggregation Inhibitors / metabolism
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prasugrel Hydrochloride / economics
  • Prasugrel Hydrochloride / therapeutic use
  • Predictive Value of Tests
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / economics*
  • Purinergic P2Y Receptor Antagonists / metabolism
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Quality-Adjusted Life Years
  • Risk Factors
  • Stroke / economics
  • Stroke / etiology
  • Ticagrelor
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / economics
  • Ticlopidine / therapeutic use
  • Time Factors
  • Treatment Outcome
  • United States

Substances

  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Prasugrel Hydrochloride
  • Ticagrelor
  • Adenosine
  • Ticlopidine