RESUMO
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.
Assuntos
Síndrome Coronariana Aguda/economia , Síndrome Coronariana Aguda/terapia , Citocromo P-450 CYP2C19/genética , Custos de Medicamentos , Intervenção Coronária Percutânea/economia , Testes Farmacogenômicos/economia , Variantes Farmacogenômicos , Inibidores da Agregação Plaquetária/economia , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/economia , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Síndrome Coronariana Aguda/enzimologia , Síndrome Coronariana Aguda/genética , Adenosina/análogos & derivados , Adenosina/economia , Adenosina/uso terapêutico , Clopidogrel , Simulação por Computador , Trombose Coronária/economia , Trombose Coronária/etiologia , Análise Custo-Benefício , Citocromo P-450 CYP2C19/metabolismo , Técnicas de Apoio para a Decisão , Genótipo , Hemorragia/induzido quimicamente , Hemorragia/economia , Humanos , Modelos Econômicos , Método de Monte Carlo , Infarto do Miocárdio/economia , Infarto do Miocárdio/etiologia , Seleção de Pacientes , Fenótipo , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/metabolismo , Cloridrato de Prasugrel/economia , Cloridrato de Prasugrel/uso terapêutico , Valor Preditivo dos Testes , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/metabolismo , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/etiologia , Ticagrelor , Ticlopidina/análogos & derivados , Ticlopidina/economia , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
Prasugrel is a third-generation thienopyridine which selectively inhibits the platelet P2Y(12) receptor more rapidly, more potently, and with less interindividual response variability compared with the second-generation thienopyridine clopidogrel. Large-scale phase III clinical testing showed that in high-to moderate-risk acute coronary syndrome patients undergoing percutaneous coronary intervention, prasugrel translates into a greater reduction in ischemic events, including stent thrombosis, in the short and long term compared to clopidogrel. Prasugrel, however, is associated with an increased risk of major bleeding, which is more pronounced in certain patient subgroups. The ideal patient population for prasugrel use are those patients without prior transient ischemic attack/stroke, <75 years of age and >60 kg in whom the greatest ischemic benefit is achieved without a significant increase in major bleeding risk. Dose modifications in specific populations or at given time-points may represent an avenue to minimize bleeding risk and therefore maximize the clinical benefit of prasugrel. Ongoing clinical studies with prasugrel will better define the safety and efficacy profiles of this agent and potentially set the basis for new indications for use.