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

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.

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.

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.