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
M Biswas, SK Kali.

KEYWORDS
stable CAD; CYP2C19 lost of function; MACE

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<0.05 was considered statistically significant.

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.