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CYP2C19-Guided Antiplatelet Therapy After PCI
Quick Takes
- Among East Asians, approximately 60% of patients were intermediate or poor clopidogrel metabolizers based on CYP2C19 genotype testing.
- Intermediate or poor metabolizers (higher platelet reactivity) had a higher risk of cardiac death, MI, and stent thrombosis at 5 years of follow-up compared with those who were rapid or normal metabolizers.
- Prognostic impact of CYP2C19 genotyping was higher among patients with ACS and in the early phase (within 1 year) after DES implantation.
Study Questions:
What are long-term outcomes of patients undergoing clopidogrel-based antiplatelet therapy after drug-eluting stent (DES) implantation according to CYP2C19 genotypes?
Methods:
From the nationwide multicenter PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) consortium, patients who underwent CYP2C19 genotyping were selected and classified according to CYP2C19 loss-of-function allele: rapid metabolizers (RMs) or normal metabolizers (NMs) versus intermediate metabolizers (IMs) or poor metabolizers (PMs). The primary outcome was a composite of cardiac death, myocardial infarction (MI), and stent thrombosis at 5 years after the index procedure.
Results:
Of 8,163 patients with CYP2C19 genotyping, 56.7% presented with acute coronary syndrome (ACS). There were 3,098 (37.9%) in the RM or NM group, 3,906 (47.9%) in the IM group, and 1,159 (14.2%) in the PM group. IMs or PMs were associated with an increased risk of the 5-year primary outcome compared with RMs or NMs (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [CI], 1.01-1.98; p = 0.041), and the effect was more pronounced in the first year (aHR, 1.67; 95% CI, 1.10-2.55; p = 0.016). The prognostic implication of being an IM and PM was significant in ACS patients (aHR, 1.88; 95% CI, 1.20-2.93; p = 0.005) but not in those with stable angina (aHR, 0.92; 95% CI, 0.54-1.55; p = 0.751) (p for interaction = 0.028).
Conclusions:
Among East Asians with clopidogrel-based antiplatelet therapy after DES implantation, CYP2C19 genotyping could stratify patients who were likely to have an increased risk of atherothrombotic events.
Perspective:
The current study investigated the long-term outcomes of clopidogrel-based antiplatelet therapy after DES implantation in East Asians according to CYP2C19 genotypes. Intermediate or poor metabolizers (higher platelet reactivity) had a higher risk of cardiac death, MI, and stent thrombosis at 5 years of follow-up compared to those who were rapid or normal metabolizers. The prognostic impact of CYP2C19 genotyping was more pronounced among patients with ACS compared to stable angina and in the early phase (1 year) post-intervention. Genotype-guided management of antiplatelet therapy may be useful in select patients.
Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Interventions and ACS, Chronic Angina
Keywords: Acute Coronary Syndrome, Angina, Stable, Clopidogrel, Cytochrome P-450 CYP2C19, Drug-Eluting Stents, Genotype, Myocardial Infarction, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Thrombosis
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