Key result
CYP2C19 loss-of-function gene linked to ~184% higher ISR risk after stenting vs wild-type.
Why the study?
The association between the CYP2C19 loss of function gene and in-stent restenosis after coronary stenting remained controversial due to conflicting results and small population sizes in previous studies.
Does the CYP2C19 loss of function (LOF) gene increase the risk of in-stent restenosis in patients treated with clopidogrel after coronary stenting?
Meta-Analysis (n=284)
Does the CYP2C19 loss of function (LOF) gene increase the risk of in-stent restenosis in patients treated with clopidogrel after coronary stenting?
Effect estimate: OR 2.84 (95% CI 1.54-5.24)
Absolute Event Rate: 51.3% vs 33.5%
p-value: p=0.0008
Patients with CYP2C19 loss of function alleles treated with clopidogrel have a significantly higher risk of developing in-stent restenosis after coronary stenting.
May inform alternative P2Y12 inhibitor selection in CYP2C19 LOF carriers post-stenting; leaves open impact on outcomes in prospective trials.
<ns3:p> <ns3:bold>Background: </ns3:bold> 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. </ns3:p> <ns3:p> <ns3:bold>Methods:</ns3:bold> A systematic online database search was performed until April 2021. The primary outcome was ISR and assessed using OR with 95% CI. Publication bias was assessed using the Newcastle Ottawa Scale. <ns3:italic> I <ns3:sup>2</ns3:sup> </ns3:italic> was applied to examine heterogeneities among the studies. </ns3:p> <ns3:p> <ns3:bold>Results:</ns3:bold> 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, 40 patients had an ISR. Meanwhile, of the 206 patients with a wild-type gene, 69 patients had an ISR. The LOF gene was associated with a higher risk of ISR (OR 95% CI = 2.84 [1.54–5.24], <ns3:italic>p</ns3:italic> = 0.0008). A major limitation in our study was the small number of previous studies and small sample sizes. </ns3:p> <ns3:p> <ns3:bold>Conclusions:</ns3:bold> Patients with LOF genes, regardless of the allele variation, treated with clopidogrel, had a higher risk of developing ISR after coronary stenting. </ns3:p>
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Pintaningrum et al. (2022) conducted a meta-analysis in Coronary in-stent restenosis (n=284). CYP2C19 loss of function (LOF) genotype vs. CYP2C19 wild-type genotype was evaluated on In-stent restenosis (ISR) (OR 2.84, 95% CI 1.54-5.24, p=0.0008). The presence of the CYP2C19 loss of function gene was associated with a significantly higher risk of in-stent restenosis after coronary stenting compared to the wild-type gene (OR 2.84).
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