Meta-Analysis of Cytochrome P450 2C19 Polymorphism and Risk of Adverse Clinical Outcomes Among Coronary Artery Disease Patients of Different Ethnic Groups Treated With Clopidogrel

Jang, Jae‐Sik; Cho, Kyoung-Im; Jin, Han-Young; Seo, Jeong-Sook; Yang, Tae–Hyun; Kim, Dae-Kyeong; Kim, Dong-Soo; Seol, Sang–Hoon; Kim, Doo-Il; Kim, Bo‐Hyun; Park, Yong Hyun; Je, Hyung-Gon; Jeong, Young‐Hoon; Lee, Seung-Whan

doi:10.1016/j.amjcard.2012.04.020

Cited by 94 publications

(77 citation statements)

References 26 publications

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“…The mutual culture "shock" between host and refugee culture and transcultural aspects of public health ( 71 ), and biological aspects such as cytochromes and competition or interaction between traditional and "western" medicines are additional factors ( 72,73 ) as outlined before. Rehabilitation especially in severe PTSD can be a major challenge as (re-)integration might be inhibited ( 74 ( 82 ), again using the Common Elements Treatment Approach (CETA).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Facing Violence – A Global Challenge

Wenzel

Kienzler

Wollmann

2015

Psychiatric Clinics of North America

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Violence has been shown lead to a global challenge leading to long lasting social, medical and mental health sequels. In this article we focus on massive social violence affecting groups such as war and civil war. Models developed in Western Europe and North America for understanding trauma related health problems and developing interventions cannot be sufficient to address this global health challenge. Culture is an important aspect of this challenge. Revisions of the APAs Diagnostical and Statistical Manual in DSM V, the discussion of dimensional approaches, new approaches in public mental and community health and closer interdisciplinary collaboration indicate a paradigm shift that reflects the complexity of issues. In displaced populations, the benefit of flight might be unbalanced by further problems due to forced migration. Social suffering and mental health problems related to violence as a global public health problem can only be tackled with a holistic approach that takes cultural, social, legal and economic determinants into account, and might also need a strong focus on human rights. Research that can give a reliable assessment of complex long term outcomes is still largely missing, and can be seen as a major and complex challenge for future research. Key points:• Sequels to violence can, due to their high prevalence and potentially severe long term impact, be seen globally as the potentially largest mental health challenge.• Displacement can add additional challenges for victims and health care systems.• An interdisciplinary approach integrating medical, and psychological but also legal and sociological aspects is required to address understanding, treating and preventing violence.• A stronger focus on subjective, culture based and dimensional factors, as partly reflected in the new DSM V models, needs to be part of any intervention.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Facing Violence – A Global Challenge

Wenzel

Kienzler

Wollmann

2015

Psychiatric Clinics of North America

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“…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.…”

Section: Heterogeneitymentioning

confidence: 99%

“…[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).…”

Section: Systematic Reviewmentioning

confidence: 99%

“…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.…”

Section: Bias Assessmentmentioning

confidence: 99%

“…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.…”

Section: Meta-analyses Characteristicsmentioning

confidence: 99%

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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

Osnabrugge

Head

Zijlstra

et al. 2015

Genetics in Medicine

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Clopidogrel, in combination with aspirin, is a standard treatment for patients with acute coronary syndrome and is one of the top-selling drugs in the world.1,2 However, there is substantial interindividual variability in response. Polymorphisms of the cytochrome P450 (CYP) gene have been identified as a potential risk factor for nonresponse.3 This gene plays a central role in drug-metabolizing processes in the liver, and clopidogrel makes use of these processes to transform into an active metabolite capable of inhibiting platelet aggregation. Identification of CYP2C19 polymorphisms could lead to personalized treatment based on genotype in patients with acute coronary syndrome, and therefore, the US Food and Drug Administration recommends CYP2C19 genotyping for individualized antiplatelet management. 4 The association between CYP2C19 loss-of-function alleles and clinical efficacy of clopidogrel has been studied extensively, and several meta-analyses have summarized the results of those studies.5-8 Systematic reviews and meta-analyses are often considered the highest level of evidence, 9-11 and their popularity in the cardiovascular field increased almost 13 times as fast as the increase in number of published randomized clinical trials. 12However, the interpretation of meta-analyses is confusing when the conclusions of overlapping meta-analyses are discordant. Some meta-analyses on CYP2C19 loss-of-function and clinical efficacy of clopidogrel conclude that the association is proven, 7,8 whereas others conclude the opposite. 5,6 Our objective was to systematically evaluate the discordant evidence for the association between CYP2C19 loss-offunction alleles and clinical efficacy of clopidogrel through a critical methodological appraisal of published meta-analyses. MATERIALS AND METHODSOur review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, 13 and we consulted the Cochrane Handbook for Systematic Reviews of Interventions for methodological aspects of meta-analyses. We systematically investigated how 11 overlapping meta-analyses on the association between CYP2C19 loss-of-function alleles and clinical efficacy of clopidogrel could yield contradictory outcomes. The results of the meta-analyses differed because more recent metaanalyses included more primary studies and some had not included conference abstracts. Conclusions differed because between-study heterogeneity and publication bias were handled differently across meta-analyses. All meta-analyses on the clinical end point observed significant heterogeneity and several reported evidence for publication bias, but only one out of eight statistically significant meta-analyses concluded that therefore the association was unproven and one other refrained from quantifying a pooled estimate because of heterogeneity. For the end point stent thrombosis, all meta-analyses reported statistically significant associations with CYP2C19 loss-of-function alleles with no statistically significant evidence for heterogeneity, b...

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Modulation of CYP450 Activities in Patients With Type 2 Diabetes

Gravel

Chiasson

Turgeon

et al. 2019

Clin Pharma and Therapeutics

101

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We conducted a comprehensive in vivo study evaluating the influence of type 2 diabetes (T2D) on major cytochrome P450 (CYP450) activities. These activities were assessed in 38 T2D and 35 non-T2D subjects after a single oral administration of a cocktail of probe drugs: 100 mg caffeine (CYP1A2), 100 mg bupropion (CYP2B6), 250 mg tolbutamide (CYP2C9), 20 mg omeprazole (CYP2C19), 30 mg dextromethorphan (CYP2D6), 2 mg midazolam (CYP3As), and 250 mg chlorzoxazone (alone; CYP2E1). Mean metabolic activity for CYP2C19, CYP2B6, and CYP3A was decreased in subjects with T2D by about 46%, 45%, and 38% (P < 0.01), respectively. CYP1A2 and CYP2C9 activities seemed slightly increased in subjects with diabetes, and no difference was observed for CYP2D6 or CYP2E1 activities. Several covariables, such as inflammatory markers (interleukin (IL)-1ß, IL-6, gamma interferon, and tumor necrosis factor alpha), genotypes, and diabetes-related and demographic-related factors were considered in our analyses. Our results indicate that low chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform-specific manner.

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Meta-Analysis of Cytochrome P450 2C19 Polymorphism and Risk of Adverse Clinical Outcomes Among Coronary Artery Disease Patients of Different Ethnic Groups Treated With Clopidogrel

Cited by 94 publications

References 26 publications

Facing Violence – A Global Challenge

Facing Violence – A Global Challenge

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

Modulation of CYP450 Activities in Patients With Type 2 Diabetes

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