CYP2C19 LOF and GOF Guided Antiplatelet Therapy in Patients with Acute Coronary Syndrome: A Cost Effectiveness Analysis
PurposeThis 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).MethodsA 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.ResultsBase 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.ConclusionsUsing 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.
Cardiovascular Drugs and Therapy