Frontiers in pharmacology · 2026
Risk factors for Post-PCI cardiovascular events in coronary artery disease patients treated with clopidogrel combined with aspirin.
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Zhou Jun, Wang Qiang-Sheng
Аннотация
BACKGROUND: Cytochrome P450 family two subfamily C member 19 (CYP2C19) loss-of-function (LOF) variants may influence clopidogrel response after percutaneous coronary intervention (PCI), but their prognostic relevance within combined clinical and procedural risk assessment remains incompletely defined. This study aimed to evaluate the association between CYP2C19 functional phenotype and major adverse cardiac and cerebrovascular events (MACCE) in coronary artery disease (CAD) patients receiving clopidogrel-based dual antiplatelet therapy (DAPT) after PCI.
METHOD: This retrospective observational study included 280 consecutive CAD patients who underwent PCI with stent implantation and received aspirin plus clopidogrel. The primary endpoint was time to first MACCE. Multivariable Cox proportional hazards regression was the primary analysis, with logistic regression as a secondary supportive analysis. Kaplan-Meier analysis, subgroup interaction analyses, and sensitivity analyses were performed.
RESULTS: During a median follow-up of 32.0 months, 52 patients experienced MACCE (18.6%). In the primary Cox model, older age, diabetes mellitus, lower estimated glomerular filtration rate, lower left ventricular ejection fraction, greater total stent length, post-procedural Thrombolysis In Myocardial Infarction (MI) flow <3, and CYP2C19 LOF phenotype were associated with time to first MACCE. CYP2C19 LOF remained significant after adjustment (adjusted hazard ratio 1.74, 95% confidence interval 1.10-2.75; P = 0.018). Kaplan-Meier analysis showed lower MACCE-free survival in LOF carriers than in non-LOF patients (log-rank P = 0.007). Interaction analyses suggested stronger LOF-associated risk patterns in acute coronary syndrome and complex PCI subgroups.
CONCLUSION: In clopidogrel-treated CAD patients after PCI, CYP2C19 LOF phenotype was associated with MACCE in a clinical-procedural risk framework. These findings support further prospective validation of integrated genotype-informed post-PCI risk stratification.
METHOD: This retrospective observational study included 280 consecutive CAD patients who underwent PCI with stent implantation and received aspirin plus clopidogrel. The primary endpoint was time to first MACCE. Multivariable Cox proportional hazards regression was the primary analysis, with logistic regression as a secondary supportive analysis. Kaplan-Meier analysis, subgroup interaction analyses, and sensitivity analyses were performed.
RESULTS: During a median follow-up of 32.0 months, 52 patients experienced MACCE (18.6%). In the primary Cox model, older age, diabetes mellitus, lower estimated glomerular filtration rate, lower left ventricular ejection fraction, greater total stent length, post-procedural Thrombolysis In Myocardial Infarction (MI) flow <3, and CYP2C19 LOF phenotype were associated with time to first MACCE. CYP2C19 LOF remained significant after adjustment (adjusted hazard ratio 1.74, 95% confidence interval 1.10-2.75; P = 0.018). Kaplan-Meier analysis showed lower MACCE-free survival in LOF carriers than in non-LOF patients (log-rank P = 0.007). Interaction analyses suggested stronger LOF-associated risk patterns in acute coronary syndrome and complex PCI subgroups.
CONCLUSION: In clopidogrel-treated CAD patients after PCI, CYP2C19 LOF phenotype was associated with MACCE in a clinical-procedural risk framework. These findings support further prospective validation of integrated genotype-informed post-PCI risk stratification.