Evidence map›Paper›PMID 29330256›Full record

Trial reportJournal of the American Heart Association2018

Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial.

Thor Ueland, Axel Åkerblom, Tatevik Ghukasyan, Annika E Michelsen, Pål Aukrust, Richard C Becker, Maria Bertilsson, Anders Himmelmann, Stefan K James, Agneta Siegbahn and 4 more

Registry-linked trialOpen access · goldAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of the American Heart Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00391872 (A Randomised, Double-blind, Parallel Group, Phase 3, Efficacy and Safety Study of Ticagrelor Compared With Clopidogrel for Prevention of Vascular Events in Patients With Non-ST or ST Elevation Acute Coronary Syndromes), which is not on this map. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 pooled it
0.4field-weighted citation impact, top 41% 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.

NCT00391872 phase3completednot on this map

A Randomised, Double-blind, Parallel Group, Phase 3, Efficacy and Safety Study of Ticagrelor Compared With Clopidogrel for Prevention of Vascular Events in Patients With Non-ST or ST Elevation Acute Coronary Syndromes (ACS) [PLATO- a Study of PLATelet Inhibition and Patient Outcomes]

TypeinterventionalSponsorAstraZenecaRan2006 to 2009Enrolled18,624ConditionsAcute Coronary SyndromeArmsTicagrelor, Clopidogrel
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 10 citations in OpenAlex.

  1. Antiplatelet agents for chronic kidney disease.The Cochrane database of systematic reviews · 2022
    Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
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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

14 authors at 7 institutions in 6 countries.

Thor UelandResearch Institute of Internal Medicine, The National Hospital, University of Oslo, Norway thor.ueland@medisin.uio.no.
Axel ÅkerblomDepartment of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
Tatevik GhukasyanUppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Annika E MichelsenResearch Institute of Internal Medicine, The National Hospital, University of Oslo, Norway.
Pål AukrustResearch Institute of Internal Medicine, The National Hospital, University of Oslo, Norway.
Richard C BeckerDivision of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, University of Cincinnati College of Medicine, Cincinnati, OH.
Maria BertilssonUppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Anders HimmelmannAstraZeneca Research and Development, Gothenburg, Sweden.
Stefan K JamesDepartment of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
Agneta SiegbahnUppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Robert F StoreyDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, United Kingdom.
Frederic KontnyDepartment of Cardiology, Stavanger University Hospital, Stavanger, Norway.
Lars WallentinDepartment of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
PLATO (Platelet Inhibition and Patient Outcomes) Trial Investigators
Uppsala University · SEUiT The Arctic University of Norway · NOAstraZeneca (Sweden) · SEDrammen Hospital · NOUniversity of Cincinnati Medical Center · USUniversity of Oslo · NOUniversity of Sheffield · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundElevated levels of osteoprotegerin, a secreted tumor necrosis factor-related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6 months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial. METHODS AND

resultsThe associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non-coronary artery bypass grafting major bleeding during 1 year of follow-up were assessed by Cox proportional hazards models. Event rates of the composite end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and 11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI], 1.21-1.42) for the composite end point but was not significant in adjusted analysis (ie, clinical characteristics and levels of C-reactive protein, troponin T, NT-proBNP [N-terminal pro-B-type natriuretic peptide], and growth differentiation factor-15). The corresponding rates of non-coronary artery bypass grafting major bleeding were 2.4%, 2.2%, 3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36-1.69), and a fully adjusted HR of 1.26 (95% CI, 1.09-1.46). The multivariable association between the osteoprotegerin concentrations and the primary end point after 1 month resulted in an HR of 1.09 (95% CI, 0.89-1.33); for major bleeding after 1 month, the HR was 1.33 (95% CI, 0.91-1.96).

conclusionsIn patients with acute coronary syndrome treated with dual antiplatelet therapy, osteoprotegerin was an independent marker of major bleeding but not of ischemic cardiovascular events. Thus, high osteoprotegerin levels may be useful in increasing awareness of increased bleeding risk in patients with acute coronary syndrome receiving antithrombotic therapy. CLINICAL

trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Indexed as

Acute Coronary SyndromeAgedAspirinBiomarkersClopidogrelDrug Therapy, CombinationFemaleHemorrhageHumansMaleMiddle AgedOsteoprotegerinPlatelet Aggregation InhibitorsRisk AssessmentRisk FactorsTicagrelorAspirinBiomarkersClopidogrelOsteoprotegerinPlatelet Aggregation InhibitorsTicagrelorTNFRSF11B protein, humanacute coronary syndromebleedingosteoprotegerinprognosis

Identifiers

PMID29330256
PMCPMC5850148
OpenAlexW2783580323

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

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.