Prospective Evaluation of On-Clopidogrel Platelet Reactivity Over Time in Patients Treated With Percutaneous Coronary Intervention

Campo, Gianluca; Parrinello, Giovanni; Ferraresi, Paolo; Lunghi, Barbara; Tebaldi, Matteo; Miccoli, Matteo; Marchesini, Jlenia; Bernardi, Francesco; Ferrari, Roberto; Valgimigli, Marco

doi:10.1016/j.jacc.2010.12.047

Cited by 323 publications

(252 citation statements)

References 19 publications

Supporting

Mentioning

216

Contrasting

Unclassified

Order By: Relevance

“…Subsequently, a series of publications demonstrated an increased risk for hemorrhagic complications for patients who were carriers or homozygous for the ultrarapid metabolizer allele *17. [20][21][22][23][24][25][26] Our data demonstrate that there are no statistically significant differences in the frequency of poor metabolizer alleles among self-described whites, Hispanics, African American and Ashkenazi Jews. However, Hispanics have a statistically significant lower frequency of the *17 allele than either whites or African Americans.…”

Section: Discussionmentioning

confidence: 53%

“…20 Subsequently, several studies including a large meta-analysis have confirmed that the *17 allele is a gain-of-function allele associated with increased activity of clopidogrel and increased risk of hemorrhagic events for patients treated with standard doses of clopidogrel. [21][22][23][24][25][26][27] Estradiol is also metabolized by CYP2C19. In a case-control study of 1,015 patients with breast cancer, women who were taking hormone replacement therapy for more than 10 years and carried a *17 CYP2C19 allele had a decreased risk of breast cancer (odds ratio = 0.57).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory

Strom

Goos

Crossley

et al. 2012

Genetics in Medicine

View full text Add to dashboard Cite

Purpose:We sought to determine the genotype frequencies for cytochrome p450 enzyme 2C19 variant alleles both in the US panethnic population and various US ethnic groups and to establish the frequency of clinically actionable genotypes. methods:Analytical results were obtained from 1,396 consecutive samples submitted for cytochrome p450 enzyme 2C19 genotyping tests and stored in a proprietary database. This database was queried and genotypes and predicted phenotypes established. Anonymized samples were obtained from specimens submitted for cystic fibrosis genotyping that contained ethnicity information. Samples from 357, 149, and 346 individuals self-identified as white, African American, and Hispanic, respectively, were analyzed. In addition, 342 anonymized samples submitted for Ashkenazi Jewish panel testing were analyzed.Results: Significant ethnic differences were observed in the frequencies of the *17 ultrarapid allele among the various groups studied. In the pan-ethnic population, 3.8% of tested patients were classified as ultrarapid metabolizers, 24% as extensive metabolizers heterozygous for a *17 ultrarapid allele, 27% as intermediate metabolizers, and 3.5% as poor metabolizers. Using stringent criteria, 7.3% of individuals would have clinically actionable genotypes. In addition, we detected two individuals with a haplotype of *2/*17 and a single individual with a haplotype of *4/*17 indicating that the *17 hypermetabolic allele can occur on a *1, *2, or *4 background.Genet Med 2012:14(1):95-100

show abstract

Section: Discussionmentioning

confidence: 53%

mentioning

confidence: 99%

Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory

Strom

Goos

Crossley

et al. 2012

Genetics in Medicine

View full text Add to dashboard Cite

show abstract

“…Recently, Campo et al 39) have reported that more bleeding events occurred in patients undergoing dual antiplatelet therapy with aspirin and clopidogrel after PCI with baseline P2Y12 reactivity units (PRU) of ≤ 85 (n = 15, 20% of patients with PRU ≤ 85) evaluated by VerifyNowP2Y12 (Accumetrics Inc., San Diego, CA) than those with PRU ＞85 (n = 4, 1.8% of Japanese patients receiving antithrombotic therapy 20) , the annual incidence of life threatening or major bleeding events using the same definition 21) as in the present study was 1.13% in patients treated with aspirin alone, including 60% who had had a prior ischemic stroke. The Cilostazol Stroke Prevention Study II (CSPSII) 34) , a double-blind randomized prospective study, was conducted to compare the clinical outcomes of Japanese patients with a prior ischemic stroke undergoing antiplatelet therapy with aspirin or cilostazol (a phosphodiesterase 3 inhibitor).…”

Section: Incidence Of Macces In Subgroup Of Patients Aged 70 Years Anmentioning

confidence: 98%

Impact of Platelet Reactivity on Long-term Clinical Outcomes and Bleeding Events in Japanese Patients Receiving Antiplatelet Therapy with Aspirin

Yamane¹,

Ikeda²,

Taniguchi³

et al. 2012

JAT

View full text Add to dashboard Cite

Aim:Aspirin is an antiplatelet drug widely used for the prevention of cardiovascular disease; however, it is known to increase bleeding events. A low response to aspirin was reported to correlate with poor prognosis in patients undergoing antiplatelet therapy with aspirin. The aim of this study was to evaluate the impact of the antiplatelet activity of aspirin on cardiovascular and bleeding events in Japanese patients. Methods: We analyzed the clinical course of 239 Japanese patients undergoing antiplatelet therapy with aspirin for a median of 64 months in this study. Their residual platelet reactivity was examined at enrollment and after 2 years. The co-primary endpoints were the occurrence of major adverse cardiac and cerebrovascular events (MACCEs) and bleeding events. Results: The annual incidence of MACCEs and major bleeding events was 3.7% and 0.48%, respectively. With defined criteria, 67 patients (28%) were classified as low responders based on the platelet aggregability measured at enrollment. Low response to aspirin was not associated with increased MACCEs, while it clearly increased MACCEs in patients less than 70 years old (low responders 36.9% vs. responders 14.8%, log rank p=0.008). Five major types of bleeding occurred in the responders, but not in low responders, although the difference was not statistically significant (p = 0.07). Conclusion: Low response to aspirin was not associated with the increase of long-term MACCEs, while it increased MACCEs in patients less than 70 years old; however, it tended to decrease major bleeding events in Japanese patients.

show abstract

“…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.…”

Section: -30mentioning

confidence: 99%

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

View full text Add to dashboard Cite

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...

show abstract

Prospective Evaluation of On-Clopidogrel Platelet Reactivity Over Time in Patients Treated With Percutaneous Coronary Intervention

Cited by 323 publications

References 19 publications

Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory

Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory

Impact of Platelet Reactivity on Long-term Clinical Outcomes and Bleeding Events in Japanese Patients Receiving Antiplatelet Therapy with Aspirin

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

Contact Info

Product

Resources

About