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

Abstract

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.

Evaluation of the incremental prognostic value of the combination of CYP2C19 poor metabolizer status and ABCB1 3435 TT polymorphism over conventional risk factors for cardiovascular events after drug-eluting stent implantation in East Asians

“…Our findings also supported the current guidelines, which do not recommend routine genetic testing to assess clopidogrel metabolism for patients considering treatment because of the poor sensitivity and low positive predictive value for identifying "high-risk" patients. 15,23 In fact, it is very difficult to perform large randomized studies guided by genetic testing. No data are available regarding randomized trials for genotype-guided antiplatelet therapy.…”

A systematic review and critical assessment of 11 discordant meta-analyses on reduced-function CYP2C19 genotype and risk of adverse clinical outcomes in clopidogrel users

“…5 Higher sample size and poorer quality of the primary studies were associated with lower effect sizes, 7,25 but other studies did not find an impact of study characteristics. 5,6 For ST, four metaanalyses observed moderate heterogeneity, with I 2 ranging from 32 to 44%, 5,6,24,27 but the degree of between-study heterogeneity was not statistically significant in any of the 11 meta-analyses. One meta-analysis discussed that exclusion of studies reduced heterogeneity but did not justify the exclusion on clinical grounds.…”

“…ST was typically defined according to the Academic Research Consortium definitions. 23 Five meta-analyses used a checklist to assess the quality of the primary studies, 5,7,8,24,25 and three meta-analyses used their own approach 6,26,27 or did not check the quality.…”

“…[5][6][7][8][24][25][26][27][28][29][30] Mean effect sizes (fixedeffects models) ranged from 1.77 to 3.82. One meta-analysis concluded that there was a possible association, 6 and one other meta-analysis observed the presence of heterogeneity and publication bias and downgraded the evidence ( Table 2; Supplementary Table S4 and Supplementary Appendix S1 online).…”

“…8,28 Nine meta-analyses used funnel plots to explore publication bias, [5][6][7][24][25][26]29 of which five applied additional analyses such as Harbord-Egger test, stratification analysis, and trim-and-fill analysis. [5][6][7]26,27 Six of the nine meta-analyses that assessed publication bias concluded that there was at least some evidence for bias due to selective missing studies, 5,6,[24][25][26]29 two did not find evidence for bias, 7,27 and in one meta-analysis, the results of the funnel plot were not discussed. 30 For ST, only 3 of the 11 meta-analyses reported the analyses of publication bias and concluded that presence of bias could not be ruled out.…”