Evidence map›Paper›PMID 24247616›Full record

Trial reportJAMA2014

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial.

Stephen J Nicholls, John J P Kastelein, Gregory G Schwartz, Dianna Bash, Robert S Rosenson, Matthew A Cavender, Danielle M Brennan, Wolfgang Koenig, J Wouter Jukema, Vijay Nambi and 5 more

Registry-linked trialAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in JAMA, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01130246 (VISTA-16 Trial), which is not on this map. Cited by 150 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
150citing papers in PubMed, 7 pooled it
32.8field-weighted citation impact, top 1% 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.

NCT01130246 phase3terminatednot on this map

VISTA-16 Trial: Evaluation of the Safety and Efficacy of Short-Term A-002 Treatment in Subjects With Acute Coronary Syndromes

TypeinterventionalSponsorAnthera PharmaceuticalsRan2010 to 2012Enrolled5,189ConditionsAcute Coronary SyndromeArmsA-002, varespladib methyl, Placebo
3 · Its place in the literature

Who cites it

150 citing papers in PubMed, 7 syntheses or guidelines pooled it, 333 citations in OpenAlex.

  1. Pooled it
  2. Review of OxLDL Driven Inflammatory Cell Activation.Current atherosclerosis reports · 2025
    Pooled it
  3. Pooled it
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  6. Pooled it
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  8. Trial
  9. Group IIA Secretory Phospholipase AArteriosclerosis, thrombosis, and vascular biology · 2019
    Trial
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  12. Inherited human group IVA cytosolic phospholipase A2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015
    Trial
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  14. Review
  15. Review
  16. sPLAScience advances · 2026
    Article
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  18. Article
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 10 institutions in 4 countries.

Stephen J NichollsSouth Australian Health and Medical Research Institute and University of Adelaide, Adelaide, Australia.
John J P KasteleinAcademic Medical Center, Amsterdam, the Netherlands.
Gregory G SchwartzVeterans Affairs Medical Center and University of Colorado, Colorado, Denver.
Dianna BashCleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.
Robert S RosensonIcahn School of Medicine at Mount Sinai, New York, New York.
Matthew A CavenderBrigham and Women's Hospital, Boston, Massachusetts.
Danielle M BrennanCleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.
Wolfgang KoenigUniversity of Ulm Medical Center, Ulm, Germany.
J Wouter JukemaLeiden University Medical Center, Leiden, and Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands.
Vijay NambiMichael E. DeBakey Veterans Affairs Hospital and Baylor College of Medicine, Houston, Texas.
R Scott WrightMayo Clinic, Rochester, Minnesota.
Venu MenonCleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.
A Michael LincoffCleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.
Steven E NissenCleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.
VISTA-16 Investigators
Center for Clinical Research (United States) · USAcademic Medical Center · NLBrigham and Women's Hospital · USCleveland Clinic · USIcahn School of Medicine at Mount Sinai · USLeiden University Medical Center · NLMayo Clinic · USMichael E. DeBakey VA Medical Center · USSouth Australian Health and Medical Research Institute · AUUniversität Ulm · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

importanceSecretory phospholipase A2 (sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown.

objectiveTo determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND

participantsA double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012).

interventionsParticipants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measure was a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated.

resultsAt a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95% CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95% CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS.

trial registrationclinicaltrials.gov Identifier: NCT01130246.

Indexed as

Myocardial InfarctionAcetatesAcute Coronary SyndromeAgedAngina, UnstableAtherosclerosisAtorvastatinDouble-Blind MethodEarly Termination of Clinical TrialsFemaleHeptanoic AcidsHumansIndolesKeto AcidsMaleMiddle AgedAcetatesAtorvastatinHeptanoic AcidsIndolesKeto AcidsPhospholipases APhospholipases A2, SecretoryPyrrolesvarespladib

Identifiers

PMID24247616
OpenAlexW2124964328

What OpenQuestion holds

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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.