Key result
CYP2C19 loss-of-function linked to ~74% higher MACCE risk in post-PCI patients on clopidogrel.
Why the study?
Does CYP2C19 loss-of-function phenotype increase the risk of MACCE in CAD patients receiving clopidogrel-based DAPT after PCI?
Observational (n=280)
No
Does CYP2C19 loss-of-function phenotype increase the risk of MACCE in CAD patients receiving clopidogrel-based DAPT after PCI?
In CAD patients treated with clopidogrel and aspirin after PCI, the CYP2C19 loss-of-function phenotype is associated with a significantly increased risk of major adverse cardiac and cerebrovascular events.
May inform MACCE risk stratification in clopidogrel-treated PCI patients; leaves open whether genotyping improves outcomes in RCTs.
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.
No takes yet. Share an insight, caveat, or question.
Zhou et al. (2026) conducted an observational in Coronary artery disease (CAD) post-PCI (n=280). CYP2C19 loss-of-function (LOF) phenotype vs. Non-LOF phenotype was evaluated on Time to first major adverse cardiac and cerebrovascular events (MACCE) (HR 1.74, 95% CI 1.10–2.75, p=0.018). In coronary artery disease patients treated with clopidogrel and aspirin after percutaneous coronary intervention, the CYP2C19 loss-of-function phenotype was associated with a higher risk of major adverse cardiac and cerebrovascular events (adjusted HR 1.74).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: