CYP2C19*2/ABCB1-C3435T polymorphism and risk of cardiovascular events in coronary artery disease patients on clopidogrel: Is clinical testing helpful?

Abstract

Background: Studies evaluating CYP2C19*2 and ABCB1-C3435T polymorphisms have shown conflicting results. We performed this meta-analysis to evaluate role of clinical testing for these polymorphisms in CAD patients on clopidogrel. Methods: 19,601 patients from 14 trials were analyzed. The endpoints were major adverse cardiovascular events (MACE), cardiovascular (CV) death, stent thrombosis (ST), myocardial infarction (MI), stroke and major bleeding. Combined relative risks (RR) with 95% confidence intervals (CI) were computed for each outcome by using standard methods of meta-analysis and test parameters were computed. Results: CYP2C19*2 polymorphism was associated with higher risk of MACE [RR: 1.28, CI: 1.06–1.54; p=0.009], CV death [RR: 3.21, CI: 1.65–6.23; p=0.001], MI [RR: 1.36, CI: 1.12–1.65; p=0.002], ST [RR: 2.41, CI: 1.69–3.41; p<0.001]. No difference was seen in major bleeding events [RR: 1.02, CI: 0.86–1.20; p=0.83]. Subgroup analysis showed similar results for elective PCI [RR: 1.34, CI: 1.01–1.76; p=0.03], and PCI with DES [RR: 1.53, CI: 1.029–1.269; p=0.03]. CYP2C19*2 polymorphism has very low sensitivity (28–58%), specificity (71–73%), positive predictive value (3–10%) but good negative predictive value (92–99%). ABCB1-C3435T polymorphism analysis revealed similar MACE [RR: 1.13, CI: 0.99–1.29; p=0.06], ST [RR: 0.88, CI: 0.52–1.47; p=0.63] and major bleeding [RR: 1.04, CI: 0.87–1.25; p=0.62] in both groups. Conclusion: In CAD patients on clopidogrel therapy, CYP2C19*2 polymorphism is associated with significantly increased adverse cardiovascular events. However, due to the low positive predictive value, routine genetic testing cannot be recommended at present.

Keywords

• Genetic testing
• CYP2C19*2 polymorphisms
• ABCB1-C3435T polymorphisms