Cytochrome P450 2C19*2 polymorphism and cardiovascular recurrences in patients taking clopidogrel: a meta-analysis

Pharmacogenetic testing for CYP2C19 gene polymorphism for optimization of using antiplatelet therapy in patients with ischemic heart disease

“…Згід-но Американської Асоціації Серця / Американської колегії кардіологів, фармакогенетичне тестування необхідне безпосередньо пацієнтам з груп ризику розвитку тромбозу стента [10]. Незважаючи на дове-дену ефективність, існує ряд проблем при застосу-ванні клопідогрелю в рекомендованій дозі: відносно висока частота резистентності до терапії в деяких етнічних групах, клінічно проявляється повторними тромбозами, інфарктами та інсультами, і виникнен-ням побічних ефектів у вигляді кровотеч, при при-значенні в стандартній дозі [11].…”

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

“…The percentage of all studies that were included in the meta-analysis, calculated as the percentage of all available studies at the date of the study selection, ranged from 25 to 90% for the clinical end point and from 9 to 82% for ST (Supplementary Tables S1 and S2; Supplementary Appendix S1 online). Five meta-analyses did not include conference abstracts, 5,25,[28][29][30] and all but one of the metaanalyses left out data from one or more full articles that were included in other meta-analyses (Supplementary Table S1 and Supplementary Appendix S1 online). [34][35][36][37][38][39][40][41] For example, the post hoc genetic analysis of the ACTIVE-A trial was included in only two of the seven meta-analyses that did their literature searches after the publication of the trial, 6,24 and one meta-analysis had limited the inclusion to only primary studies with a follow-up time of 6-12 months.…”

“…[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).…”

“…Six meta-analyses reduced heterogeneity by excluding one or more studies, 5,8,[24][25][26]29 and four of these found that the resulting pooled effect estimate remained unchanged. 5,8,24,26 Five meta-analyses performed stratified meta-analyses by study and population characteristics, 7,8,25,26,29 two performed metaregression, 5,20 and one inspected primary study characteristics. 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.…”

“…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.…”