Presentation (CTI)

OBJECTIVES: Clopidogrel is a prodrug that requires CYP2C19-mediated bioactivation to exert its antiplatelet effect. Patients carrying CYP2C19 loss-of-function alleles exhibit reduced responsiveness to clopidogrel, resulting in an increased risk of recurrent ischemic events following percutaneous coronary intervention (PCI). Approximately 40-50% of Asian populations harbor CYP2C19 loss-of-function variants, highlighting the clinical relevance of pharmacogenomic-guided therapy. This study evaluated the clinical and economic impact of CYP2C19 genotype-guided antiplatelet therapy compared with conventional clopidogrel-based treatment in patients with ST-elevation myocardial infarction (STEMI) undergoing PCI.
METHODS: A decision-tree model was developed to compare conventional clopidogrel therapy with CYP2C19 genotype-guided antiplatelet therapy. In the genotype-guided strategy, loss-of-function allele carriers received alternative P2Y12 inhibitors, while non-carriers continued clopidogrel therapy. Clinical pathways incorporated major adverse cardiovascular events (MACE) and associated healthcare utilization. Event probabilities were obtained from published pharmacogenomic and cardiovascular outcome studies, while direct medical costs were derived from institutional data. The decision tree was implemented as a patient-level Monte Carlo simulation in Python, evaluating 1,000 virtual STEMI patients over a 1-year time horizon. Costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), and cost per MACE avoided were estimated.
RESULTS: Among 1,000 simulated patients, conventional therapy resulted in 70 MACE compared to 36 MACE with genotype-guided therapy. Genotype-guided therapy reduced MACE by 48.6%. Mean healthcare cost per patient was ₹265,540 for conventional therapy and ₹176,057 for genotype-guided therapy, corresponding to a cost saving of ₹89,483 per patient. Genotype-guided therapy prevented 34 MACE events and generated an additional 3.4 QALYs per 1,000 patients. The cost per MACE avoided was ₹309,324, while the ICER was ₹3.09 million per QALY gained.
CONCLUSIONS: CYP2C19 genotype-guided antiplatelet therapy significantly reduced MACE and overall healthcare costs compared with conventional clopidogrel therapy. These findings support preemptive genotype testing as a precision medicine strategy for optimizing post-PCI management in STEMI patients.