Evidence map›Paper›PMID 23392654›Full record

Trial reportCirculation. Cardiovascular genetics2013

Genetic variation in PEAR1 is associated with platelet aggregation and cardiovascular outcomes.

Joshua P Lewis, Kathleen Ryan, Jeffrey R O'Connell, Richard B Horenstein, Coleen M Damcott, Quince Gibson, Toni I Pollin, Braxton D Mitchell, Amber L Beitelshees, Ruth Pakzy and 12 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Circulation. Cardiovascular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 62 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 2 pooled it
7.7field-weighted citation impact, top 2% of its field
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.

NCT00370045 phase4unknown statusnot on this map

Peri-Procedural Myocardial Infarction, Platelet Reactivity, Thrombin Generation, and Clot Strength: Differential Effects of Eptifibatide + Bivalirudin Versus Bivalirudin -The CLEAR PLATELETS-2 Study

TypeinterventionalSponsorLifeBridge HealthRan2006Enrolled200ConditionsCoronary Artery DiseaseArmsBivalirudin with and without eptifibatide
NCT00799396 phase4completednot on this map

Pharmacogenomics of Anti-Platelet Interventions (The PAPI Study)

TypeinterventionalSponsorUniversity of Maryland, BaltimoreRan2006 to 2012Enrolled682ConditionsPlatelet Aggregation Inhibitors, Coronary Heart DiseaseArmsClopidogrel, Aspirin
3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. The Impact of Single Nucleotide Polymorphisms and Other Mechanisms on Aspirin Resistance.Cardiovascular & hematological disorders drug targets · 2025
    Review
  12. G protein-coupled receptor kinase 5 regulates thrombin signaling in platelets.Research and practice in thrombosis and haemostasis · 2024
    Article
  13. Article
  14. Article
  15. Effects ofWorld journal of emergency medicine · 2024
    Article
  16. Review
  17. Using theBrain sciences · 2023
    Article
  18. Review
  19. Article
  20. Article

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 6 institutions in 1 country.

Joshua P LewisDivision of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Kathleen Ryan
Jeffrey R O'Connell
Richard B Horenstein
Coleen M Damcott
Quince Gibson
Toni I Pollin
Braxton D Mitchell
Amber L Beitelshees
Ruth Pakzy
Keith Tanner
Afshin Parsa
Udaya S Tantry
Kevin P Bliden
Wendy S Post
Nauder Faraday
William Herzog
Yan Gong
Carl J Pepine
Julie A Johnson
Paul A Gurbel
Alan R Shuldiner
Johns Hopkins University · USFlorida College · USSinai Hospital · USUniversity of Florida · USJohns Hopkins Medicine · USUnited States Department of Veterans Affairs · US

Funding

Pharmacogenomic Evaluation of Antihypertensive ResponsesU01GM074492 · NIGMS · UNIVERSITY OF FLORIDA · PI COOPER-DEHOFF, RHONDA M, JOHNSON, JULIE A. · 2005 to 2014
$20.7M
Zonulin Antibodies in Intestinal Permeabilitiy in IDDMM01RR016500 · NCRR · UNIVERSITY OF MARYLAND BALTIMORE · PI OSWALD, LYNN M · 2002 to 2009
$20.2M
Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3M
Pharmacogenomics of Anti-platlet Intervention-2 (PAPI-2) StudyU01HL105198 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI SHULDINER, ALAN R. · 2010 to 2014
$13.6M
Pharmacogenomics of CVD risk ReductionU01GM074518 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI SHULDINER, ALAN R. · 2005 to 2009
$7.3M
Hypertension PharmacogeneticsR01HL074730 · NHLBI · UNIVERSITY OF FLORIDA · PI JOHNSON, JULIE A. · 2003 to 2006
$3.4M
Genome-wide Association in Families: Data Integrity, Design and Methods IssueU01HL084756 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI O'CONNELL, JEFFREY R · 2006 to 2008
$880k
Aspirin Pharmacogenomics: Role of PEAR1 in Personalized Anti-Platelet TherapyK23GM102678 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI LEWIS, JOSHUA PATRICK · 2012 to 2016
$806k
NCRR NIH HHS M01 RR016500NCRR NIH HHS M01 RR 16500NHLBI NIH HHS R01 HL074730NHLBI NIH HHS U01 HL084756NHLBI NIH HHS U01 HL105198NIDDK NIH HHS P30 DK072488NIGMS NIH HHS K23 GM102678NIGMS NIH HHS U01 GM074492NIGMS NIH HHS U01 GM074518PHS HHS R01074730
6 · The paper itself

Abstract

BACKGROUND- Aspirin or dual antiplatelet therapy with aspirin and clopidogrel is a standard therapy for patients who are at increased risk for cardiovascular events. However, the genetic determinants of variable response to aspirin (alone and in combination with clopidogrel) are not known. METHODS AND RESULTS- We measured ex vivo platelet aggregation before and after dual antiplatelet therapy in individuals (n=565) from the Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study and conducted a genome-wide association study of drug response. Significant findings were extended by examining genotype and cardiovascular outcomes in 2 independent aspirin-treated cohorts: 227 percutaneous coronary intervention patients and 1000 patients of the International Verapamil SR/Trandolapril Study (INVEST) Genetic Substudy (INVEST-GENES). Results from the genome-wide association study revealed a strong association between single-nucleotide polymorphisms on chromosome 1q23 and post-dual antiplatelet therapyplatelet aggregation. Further genotyping revealed rs12041331 in the platelet endothelial aggregation receptor-1 (PEAR1) gene to be most strongly associated with dual antiplatelet therapy response (P=7.66×10(-9)). In white and black patients undergoing percutaneous coronary intervention, A-allele carriers of rs12041331 were more likely to experience a cardiovascular event or death compared with GG homozygotes (hazard ratio, 2.62; 95% confidence interval, 0.96-7.10; P=0.059; and hazard ratio, 3.97; 95% confidence interval, 1.10-14.31; P=0.035, respectively). In aspirin-treated INVEST-GENES patients, rs12041331 A-allele carriers had significantly increased risk of myocardial infarction compared with GG homozygotes (odds ratio, 2.03; 95% confidence interval, 1.01-4.09; P=0.048). CONCLUSION- Common genetic variation in PEAR1 may be a determinant of platelet response and cardiovascular events in patients on aspirin alone or in combination with clopidogrel. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00799396 and NCT00370045.

Indexed as

AdultAgedAllelesChromosomes, Human, Pair 1ClopidogrelCohort StudiesCoronary Artery DiseaseFemaleGenome-Wide Association StudyGenotypeHumansMaleMiddle AgedOdds RatioPlatelet AggregationPlatelet Aggregation InhibitorsClopidogrelPEAR1 protein, humanPlatelet Aggregation InhibitorsReceptors, Cell SurfaceTiclopidine

Identifiers

PMID23392654
PMCPMC3715320
OpenAlexW2169596690

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.