Key result
CYP2C19 poor metabolizer genotype is linked to ~96% higher 2-year MACCE risk vs extensive metabolizers.
Why the study?
The prognostic value of the CYP2C19 genotype in post-PCI patients remains controversial.
Does CYP2C19 poor metabolizer genotype predict increased risk of MACCE in post-PCI patients compared to extensive metabolizers?
Cohort (n=756)
Does CYP2C19 poor metabolizer genotype predict increased risk of MACCE in post-PCI patients compared to extensive metabolizers?
Effect estimate: HR 1.960 (95% CI 1.139-3.372)
Absolute Event Rate: 17.4% vs 9.2%
CYP2C19 poor metabolizer genotype is an independent predictor of MACCE at 2 years post-PCI, particularly in specific subgroups such as older males with higher SYNTAX scores.
CYP2C19 poor metabolizer status may flag higher post-PCI MACCE risk; leaves open whether genotyping should guide therapy.
Background: The prognostic value of the CYP2C19 genotype in post-percutaneous coronary intervention (PCI) patients remains controversial. The recently-published, limited-sample PHARMCLO trial indicates a personalized pharmacogenomic approach may reduce adverse events. This study aimed to determine the prognostic value of CYP2C19 genotypes.Methods: The original cohort consisted of 10,724 PCI patients in 2013. 756 patients with genotyped CYP2C19 were included in our analysis. The CYP2C19 genotype prognostic value was tested based on different clinical factors. The primary endpoint was major adverse cardio- and cerebro-vascular event (MACCE).Results: MACCE 2-years post-PCI occurred in 19 patients (17.4%) in poor metabolizers (PM, CYP2C19 *2/*2, *2/*3, *3/*3), 43 patients (12.2%) in intermediate metabolizers (IM, CYP2C19 *1/*2 or *1/*3) and 27 patients (9.2%) in extensive metabolizers (EM, CYP2C19 *1/*1). PM was an independent MACCE predictor compared with EM (HR: 1.960, 95% CI: 1.139–3.372), but the difference between IM and PM was not significant (HR: 1.314, 95% CI: 0.843–2.048). Major bleeding (BARC grade ≥3) was not significantly different between the three groups (2.5% vs. 2.1% vs. 0.8%, P=0.133). Subgroup analysis showed that the CYP2C19 genotype prognostic value was present in the following subgroups: male, age >60 years, body mass index (BMI) >24 kg/m2, SYNTAX score >15, current smokers, and patients without chronic kidney disease.Conclusions: Utilizing CYP2C19 genotype to guide post-PCI antiplatelet therapy might be appropriate in patients with the following characteristics: male, age >60 years, BMI >24 kg/m2, SYNTAX score >15, current smokers, and non-chronic kidney disease (CKD) patients.
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Wang et al. (2021) conducted a cohort in Post-percutaneous coronary intervention (PCI) (n=756). CYP2C19 poor metabolizer (PM) genotype vs. CYP2C19 extensive metabolizer (EM) genotype was evaluated on Major adverse cardio- and cerebro-vascular event (MACCE) (HR 1.960, 95% CI 1.139-3.372). CYP2C19 poor metabolizer genotype was an independent predictor of MACCE at 2 years post-PCI compared with extensive metabolizers (17.4% vs 9.2%; HR 1.960, 95% CI 1.139-3.372).
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