Key result
Twice-daily clopidogrel linked to ~85% less in-stent restenosis vs once-daily in CYP2C19 LOF patients.
Why the study?
The study was conducted to analyze the impacts of CYP2C19 polymorphism and clopidogrel dosing on in-stent restenosis after coronary stenting.
Does an increased dose of clopidogrel (75 mg twice daily) reduce in-stent restenosis in CYP2C19 LOF allele carriers after PCI?
Cohort (n=111)
Does an increased dose of clopidogrel (75 mg twice daily) reduce in-stent restenosis in CYP2C19 LOF allele carriers after PCI?
Absolute Event Rate: 6.1% vs 40.7%
Increasing the clopidogrel dose to 75 mg twice daily in CYP2C19 LOF allele carriers significantly reduces the risk of in-stent restenosis after PCI to levels comparable to non-carriers.
May support doubled clopidogrel dosing in CYP2C19 LOF carriers post-PCI; hypothesis-generating and requires randomized confirmation before practice change.
Objective: This retrospective cohort study is to analyze the impacts of CYP2C19 polymorphism and clopidogrel dosing on in-stent restenosis (ISR) after coronary stenting. Methods: Totally, 111 patients were included, who underwent percutaneous coronary intervention (PCI) with drug-eluting stent. Patients received clopidogrel treatment after the intervention on the background treatment with aspirin, based on the genotypes: 75 mg clopidogrel once each day for subjects without CYP2C19 loss-of-function (LOF) alleles (n=51; EM), 75 mg clopidogrel once each day (n=27; IM75) or twice each day (n=33; IM150) for subjects with one CYP2C19 LOF allele. ISR at 3– 18 months after coronary stenting was assessed. Results: ISR rate was significantly higher in the IM75 group (40.7%) than the EM group (11.8%). ISR rate in the IM150 group was lower than the IM75 group (6.1% vs 40.7%), and comparable to that in the EM group. Multivariate logistic regression showed that both CYP2C19 genotype and clopidogrel dosing were associated with the risk of ISR after adjusting the relevant confounding factors. ISR risk was higher in the IM patients than the EM patients. Patients with clopidogrel dose of 75 mg once each day had significantly higher risk of ISR than those with the dose of 75 mg twice each day. Conclusion: Increased dose of clopidogrel may reduce the risk of ISR after PCI in CYP2C19 LOF allele(s) carriers. The presence of CYP2C19 LOF allele(s) increases the risk of ISR after stenting, which could be counteracted by the increased dose of clopidogrel.
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Zhang et al. (2020) conducted a cohort in in-stent restenosis after coronary stenting (n=111). Clopidogrel vs. Clopidogrel 75 mg once each day was evaluated on in-stent restenosis (ISR). In patients with a CYP2C19 LOF allele, an increased clopidogrel dose of 75 mg twice daily reduced the rate of in-stent restenosis compared to 75 mg once daily (6.1% vs 40.7%).
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