Key result
CYP2C19 loss-of-function linked to ~171% higher in-stent restenosis risk with clopidogrel versus wild-type.
Why the study?
The association between CYP2C19 loss of function genes and in-stent restenosis after coronary stenting remains controversial due to previous conflicting studies with small population sizes.
Does the CYP2C19 LOF gene increase the risk of in-stent restenosis in patients treated with clopidogrel after coronary stenting?
Meta-Analysis (n=284)
Does the CYP2C19 LOF gene increase the risk of in-stent restenosis in patients treated with clopidogrel after coronary stenting?
Effect estimate: OR 2.71 (95% CI 1.42-5.16)
Absolute Event Rate: 48.7% vs 33.5%
p-value: p=0.003
Patients with CYP2C19 loss of function alleles treated with clopidogrel have a significantly higher likelihood of developing in-stent restenosis after coronary stenting.
May prompt alternative P2Y12 inhibitors in CYP2C19 LOF carriers post-stenting; leaves open need for prospective outcome trials.
<ns4:p>Background In-stent restenosis (ISR) remains a major drawback in coronary stenting. The association between the CYP2C19 loss of function (LOF) gene and the prevalence of ISR after coronary stenting remains controversial. Previous studies have produced conflicting results and have been limited by their small population sizes. We conducted this systematic review and meta-analysis to determine the association between the presence of the CYP2C19 LOF gene and the prevalence of ISR. Methods A systematic online database search was performed until April 2021. The primary outcome was ISR and assessed using OR with 95% CI. Quality of the study was assessed using the Newcastle Ottawa Scale. <ns4:italic>I<ns4:sup>2</ns4:sup> </ns4:italic> was applied to examine heterogeneities among the studies. Results A total of 284 patients (four non-randomized controlled trial studies) were included in this study. Two hundred and six patients had wild-type genotypes, while 78 patients had the LOF genotype. Among the 78 patients with the LOF gene, 38 patients had an ISR. Meanwhile, of the 206 patients with a wild-type gene, 69 patients had an ISR. LOF gene was associated with a higher risk of ISR (OR 95% CI = 2.71 [1.42–5.16], P = 0.003). However, study-specific variability should be considered when applying these findings clinically. Conclusions Patients with LOF genes, regardless of the allele variation, treated with clopidogrel, had a higher likelihood of ISR after coronary stenting.</ns4:p>
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Pintaningrum et al. (2025) conducted a meta-analysis in Coronary in-stent restenosis (n=284). CYP2C19 loss of function (LOF) gene vs. Wild-type CYP2C19 gene was evaluated on In-stent restenosis (OR 2.71, 95% CI 1.42-5.16, p=0.003). Patients with the CYP2C19 loss of function gene treated with clopidogrel had a significantly higher risk of in-stent restenosis after coronary stenting compared to those with the wild-type gene (OR 2.71).
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