Association of CYP2C19 Loss-of-Function Alleles with Major Adverse Cardiovascular Events of Clopidogrel in Stable Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention: Meta-analysis

Purpose It was aimed to determine the aggregated risk of MACE (major adverse cardiovascular events) in stable CAD patients carrying CYP2C19 LoF alleles taking clopidogrel. Methods Literature was searched in different databases for relevant studies. Aggregated risk was estimated using a fixed/random effect model where p-value Results In total, 21 studies with 16,194 stable CAD patients were assessed. It was found that patients treated with clopidogrel carrying either one or two CYP2C19 LoF alleles who underwent PCI were associated with significantly increased risk of MACE compared to non-carriers (OR: 1.71, 95% CI: 1.51-1.94, p<0.00001) that was driven from cardiovascular death (OR: 1.43, 95% CI: 1.02-1.99, p=0.04), myocardial infarction (OR: 1.75, 95% CI: 1.42-2.16, p<0.00001), stroke (OR: 2.30, 95% CI: 1.52-3.47, p<0.0001), and stent thrombosis (OR: 4.08, 95% CI: 2.52-6.61, p<0.00001). It was also found that carriers of two CYP2C19 LoF alleles were associated with a significantly marked risk of MACE than non-carriers (OR: 2.22, 95% CI: 1.60-3.09, p<0.00001). Furthermore, the increased risk of MACE remained markedly significant in Asian patients (OR: 2.03, 95% CI: 1.72-2.40, p<0.00001) and was less significant in western patients (OR: 1.35, 95% CI: 1.11-1.63, p=0.002). Bleeding events were not significantly different in carriers of CYP2C19 LoF alleles compared to non-carriers (OR: 1.11, 95% CI: 0.85-1.45, p=0.43). Conclusion Stable CAD patients treated with clopidogrel and carried CYP2C19 LoF alleles undergoing PCI were associated with significantly increased risk of MACE compared to non-carriers, even markedly significant for Asian patients.

Automated summary

The study showed that stable CAD patients treated with clopidogrel and carrying CYP2C19 LoF alleles undergoing PCI had a significantly increased risk of MACE compared to non-carriers, especially for Asian patients.