Key result
While overall adverse events did not differ significantly, among patients with a CYP2C19 loss-of-function allele, clopidogrel use was associated with a significantly higher risk of the primary composite outcome compared to prasugrel (adjusted HR 3.19).
Why the study?
The association between CYP2C19 genotypes and adverse events in Japanese patients treated with clopidogrel or prasugrel after PCI was unclear.
Does clopidogrel compared to prasugrel increase adverse events in Japanese patients with CYP2C19 loss-of-function alleles undergoing PCI?
Observational (n=410)
Single-blind
No
Does clopidogrel compared to prasugrel increase adverse events in Japanese patients with CYP2C19 loss-of-function alleles undergoing PCI?
In Japanese patients undergoing PCI, clopidogrel is associated with a higher risk of adverse cardiovascular events compared to prasugrel specifically in those with CYP2C19 loss-of-function alleles.
BACKGROUND: The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear. METHODS AND RESULTS: This study consisted of 1,580 patients whoseCYP2C19genotypes were assessed at Shiga University of Medical Science Hospital, and 193 clopidogrel-treated and 217 prasugrel-treated patients who were followed more than 1 year after receiving PCI were analyzed. Among 1,580 patients, the prevalence of normal, intermediate, and poor metabolizers was 32%, 49%, and 17%, respectively. Overall incidence of the primary outcome, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic stroke, or major bleeding was not significantly different between the clopidogrel and prasugrel groups (adjusted hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.85-4.61, P=0.12). Among patients with theCYP2C19loss-of-function (LOF) allele, however, the incidence of the primary outcome was significantly higher in the clopidogrel group (adjusted HR 3.19, 95% CI 1.10-9.24, P=0.03), whereas no difference was observed among patients without theCYP2C19LOF allele (adjusted HR 0.67, 95% CI 0.14-3.26, P=0.62). CONCLUSIONS: Among patients with theCYP2C19LOF allele, the use of clopidogrel was significantly associated with increased adverse events. Thus, further investigation is needed to establish the practical use ofCYP2C19genotyping.
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Sawayama et al. (2020) conducted an observational in Percutaneous coronary intervention (PCI) (n=410). Clopidogrel vs. Prasugrel (3.75 mg/day) was evaluated on Composite of cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic stroke, or major bleeding (BARC 3 or 5) at 1 year (adjusted HR 1.98, 95% CI 0.85-4.61, p=0.12). While overall adverse events did not differ significantly, among patients with a CYP2C19 loss-of-function allele, clopidogrel use was associated with a significantly higher risk of the primary composite outcome compared to prasugrel (adjusted HR 3.19).
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