Evidence map›Paper›PMID 21170047›Full record

ArticleNature medicine2011

Paraoxonase-1 is a major determinant of clopidogrel efficacy.

Heleen J Bouman, Edgar Schömig, Jochem W van Werkum, Janna Velder, Christian M Hackeng, Christoph Hirschhäuser, Christopher Waldmann, Hans-Günther Schmalz, Jurriën M ten Berg, Dirk Taubert

Erratum issued Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02707445 (Prospective Multi-center Registry of Genotyping Related Clopidogrel in Percutaneous Coronary Intervention Patients), which is not on this map. Cited by 168 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed, 13 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02707445 nacompletednot on this map

Prospective Multi-center Registry of Genotyping Related Clopidogrel in Percutaneous Coronary Intervention Patients

TypeinterventionalSponsorKorea University Anam HospitalRan2011 to 2016Enrolled5,000ConditionsMyocardial Ischemia, CLOPIDOGREL, POOR METABOLISM of (Disorder)ArmsClopidogrel
3 · Its place in the literature

Who cites it

168 citing papers in PubMed, 13 syntheses or guidelines pooled it.

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  6. CYP2C19 polymorphism and clinical outcomes among patients of different races treated with clopidogrel: A systematic review and meta-analysis.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2015
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  16. Association of CYP2C19 Polymorphism with Clopidogrel Resistance in Patients with Acute Coronary Syndrome in China.Medical science monitor : international medical journal of experimental and clinical research · 2019
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108 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Heleen J BoumanDepartment of Cardiology, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands.
Edgar Schömig
Jochem W van Werkum
Janna Velder
Christian M Hackeng
Christoph Hirschhäuser
Christopher Waldmann
Hans-Günther Schmalz
Jurriën M ten Berg
Dirk Taubert

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clinical efficacy of the antiplatelet drug clopidogrel is hampered by its variable biotransformation into the active metabolite. The variability in the clinical response to clopidogrel treatment has been attributed to genetic factors, but the specific genes and mechanisms underlying clopidogrel bioactivation remain unclear. Using in vitro metabolomic profiling techniques, we identified paraoxonase-1 (PON1) as the crucial enzyme for clopidogrel bioactivation, with its common Q192R polymorphism determining the rate of active metabolite formation. We tested the clinical relevance of the PON1 Q192R genotype in a population of individuals with coronary artery disease who underwent stent implantation and received clopidogrel therapy. PON1 QQ192 homozygous individuals showed a considerably higher risk than RR192 homozygous individuals of stent thrombosis, lower PON1 plasma activity, lower plasma concentrations of active metabolite and lower platelet inhibition. Thus, we identified PON1 as a key factor for the bioactivation and clinical activity of clopidogrel. These findings have therapeutic implications and may be exploited to prospectively assess the clinical efficacy of clopidogrel.

Indexed as

StentsAmino Acid SubstitutionAryldialkylphosphataseBiotransformationClopidogrelCoronary DiseaseFollow-Up StudiesGenotypeHomozygoteHumansKineticsPlatelet Aggregation InhibitorsPolymorphism, GeneticSubstrate SpecificitySurvival AnalysisTiclopidineAryldialkylphosphataseClopidogrelPlatelet Aggregation InhibitorsPON1 protein, humanTiclopidine

Identifiers

PMID21170047

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.