Clinical Outcomes and Sustainability of Using CYP2C19 Genotype–Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

Supplemental Digital Content is available in the text. Background: <italic>CYP2C19</italic> loss-of-function (LOF) alleles impair clopidogrel effectiveness after percutaneous coronary intervention. The feasibility, sustainability, and clinical impact of using <italic>CYP2C19</italic> genotype–guided dual antiplatelet therapy (DAPT) selection in practice remains unclear. Methods: A single-center observational study was conducted in 1193 patients who underwent percutaneous coronary intervention and received DAPT after implementation of an algorithm that recommends <italic>CYP2C19</italic> testing in high-risk patients and alternative DAPT (prasugrel or ticagrelor) in LOF allele carriers. The frequency of genotype testing and alternative DAPT selection were the primary implementation end points. Risk of major adverse cardiovascular or cerebrovascular and clinically significant bleeding events over 12 months were compared across genotype and DAPT groups by proportional hazards regression. Results: <italic>CYP2C19</italic> genotype was obtained in 868 (72.8%) patients. Alternative DAPT was prescribed in 186 (70.7%) LOF allele carriers. <italic>CYP2C19</italic> testing (<italic>P</italic><0.001) and alternative DAPT use in LOF allele carriers (<italic>P</italic>=0.001) varied over time. Risk for major adverse cardiovascular or cerebrovascular was significantly higher in LOF carriers prescribed clopidogrel versus alternative DAPT (adjusted hazard ratio, 4.65; 95% confidence interval, 2.22–10.0; <italic>P</italic><0.001), whereas no significant difference was observed in those without a LOF allele (adjusted hazard ratio, 1.37; 95% confidence interval, 0.72–2.85; <italic>P</italic>=0.347). Bleeding event rates were similar across groups (log-rank <italic>P</italic>=0.816). Conclusions: Implementing <italic>CYP2C19</italic> genotype–guided DAPT is feasible and sustainable in a real-world setting but challenging to maintain at a consistently high level of fidelity. The higher risk of major adverse cardiovascular or cerebrovascular associated with clopidogrel use in <italic>CYP2C19</italic> LOF allele carriers suggests that use of genotype-guided DAPT in practice may improve clinical outcomes. [ABSTRACT FROM AUTHOR]