Risk of major adverse cardiovascular events in CYP2C19 LoF genotype guided clopidogrel against alternative antiplatelets for CAD patients undergoing PCI: Meta-analysis

Abstract

Selection of rational antagonists of P2Y₁₂ receptor for CAD patients who inherit CYP2C19 LoF alleles remains still conflicting. This study compared the clinical outcomes in CAD patients inheriting CYP2C19 LoF alleles undergoing PCI and treated with clopidogrel against alternative antagonists of P2Y₁₂ receptor. A thorough literature search was performed across multiple scientific databases following the PRISMA guidelines and PICO model. Setting the statistical significance at p < 0.05 and RevMan software was used to calculate the risk ratios (RRs). Estimation of the pooled analysis revealed a significant 62% increased risk of major adverse cardiovascular events (MACE) in CAD patients inheriting CYP2C19 LoF alleles and treated with clopidogrel against those treated with alternative P2Y₁₂ receptor antagonists such as prasugrel or ticagrelor (RR 1.62; 95% CI 1.42–1.86; p < 0.00001). In addition, Asian CAD patients were found at a significantly higher risk of MACE (RR 1.93; 95% CI: 1.49–2.49; p < 0.00001) juxtaposed to CAD patients of other ethnicities (RR 1.51; 95% CI: 1.29–1.78; p < 0.00001). Conversely, between these two treatment groups, taking clopidogrel against prasugrel/ticagrelor, who possess CYP2C19 LoF alleles, no significant differences in bleeding events were observed (RR 0.94; 95% CI 0.79–1.11; p = 0.47). CAD patients undergoing PCI who inherited CYP2C19 LoF alleles and treated with clopidogrel were associated with significantly higher risk of MACE against those treated with alternative antagonists of P2Y₁₂ receptor, that is, prasugrel or ticagrelor.