Introduction: The effects of the ABCB1 C3435T genetic polymorphism on clopidogrel responses are conflicting and inconclusive especially in patients undergoing percutaneous coronary intervention (PCI). This study examined the pooled risk of major adverse cardiovascular events (MACE) and bleeding events associated with the ABCB1 C3435T polymorphism in acute coronary syndrome or coronary artery disease patients undergoing PCI and treated with clopidogrel.
Areas covered: Literature was searched in different resources for eligible studies. The pooled risk ratio was measured using RevMan software, with p<0.05 (two-sided) set as statistically significant.
Expert opinion: The ABCB1 C3435T homozygous mutant (TT) was associated with significantly increased risk of MACE compared to either wild type genotype (CC) or the combination of wild type and heterozygous genotypes (TT vs. CC: RR 1.33; 95% CI 1.06-1.68; p=0.02; TT vs. CC+CT: RR 1.32; 95% CI 1.10-1.60; p=0.004). Safety outcomes, i.e. bleeding events were not significantly different between the genetic models investigated (TT vs. CC: RR 1.93; 95% CI 0.86-4.35; p=0.11; TT vs. CC+CT: RR 1.36; 95% CI 0.89-2.09; p=0.16; CT+TT vs. CC: RR 1.20; 95% CI 0.59-2.44; p=0.61). It is suggested that ABCB1 C3435T genotype should be tested for ACS/CAD patients undergoing PCI to ensure optimum therapy of clopidogrel.
Keywords: ABCB1 genetic polymorphism; P-glycoprotein; clopidogrel; efficacy and safety; precision medicine.