Evidence map›Paper›PMID 28656542›Full record

Trial reportCardiovascular drugs and therapy2017

Identifying Subpopulations with Distinct Response to Treatment Using Plasma Biomarkers in Acute Heart Failure: Results from the PROTECT Trial : Differential Response in Acute Heart Failure.

Licette C Y Liu, Mattia A E Valente, Douwe Postmus, Christopher M O'Connor, Marco Metra, Howard C Dittrich, Piotr Ponikowski, John R Teerlink, Gad Cotter, Beth Davison and 7 more

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cardiovascular drugs and therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 18% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. Stratified treatment recommendation or one-size-fits-all? A health economic insight based on graphical exploration.The European journal of health economics : HEPAC : health economics in prevention and care · 2019
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  2. Review
  3. 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

17 authors at 11 institutions in 5 countries.

Licette C Y LiuDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Mattia A E ValenteDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Douwe PostmusDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Christopher M O'ConnorInova Heart and Vascular Institute, Falls Church, VA, USA.
Marco MetraUniversity of Brescia, Brescia, Italy.
Howard C DittrichCardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Piotr PonikowskiMedical University, Clinical Military Hospital, Wroclaw, Poland.
John R TeerlinkUniversity of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
Gad CotterMomentum Research, Durham, NC, USA.
Beth DavisonMomentum Research, Durham, NC, USA.
John G F ClelandImperial College, London, UK.
Michael M GivertzHarvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Daniel M BloomfieldMerck Research Laboratories, Rahway, NJ, USA.
Dirk J van VeldhuisenDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Hans L HillegeDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Peter van der MeerDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Adriaan A VoorsDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. A.A.Voors@umcg.nl.
University of Groningen · NLUniversity Medical Center Groningen · NLMomentum Research · USAlaska Heart and Vascular Institute · USHarvard University · USImperial College London · GBMerck & Co., Inc., Rahway, NJ, USA (United States) · USSan Francisco VA Medical Center · USUniversity of Brescia · ITUniversity of Iowa · USWroclaw Medical University · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOver the last 50 years, clinical trials of novel interventions for acute heart failure (AHF) have, with few exceptions, been neutral or shown harm. We hypothesize that this might be related to a differential response to pharmacological therapy.

methodsWe studied the magnitude of treatment effect of rolofylline across clinical characteristics and plasma biomarkers in 2033 AHF patients and derived a biomarker-based responder sum score model. Treatment response was survival from all-cause mortality through day 180.

resultsIn the overall study population, rolofylline had no effect on mortality (HR 1.03, 95% CI 0.82-1.28, p = 0.808). We found no treatment interaction across clinical characteristics, but we found interactions between several biomarkers and rolofylline. The biomarker-based sum score model included TNF-R1α, ST2, WAP four-disulfide core domain protein HE4 (WAP-4C), and total cholesterol, and the score ranged between 0 and 4. In patients with score 4 (those with increased TNF-R1α, ST2, WAP-4C, and low total cholesterol), treatment with rolofylline was beneficial (HR 0.61, 95% CI 0.40-0.92, p = 0.019). In patients with score 0, treatment with rolofylline was harmful (HR 5.52, 95% CI 1.68-18.13, p = 0.005; treatment by score interaction p < 0.001). Internal validation estimated similar hazard ratio estimates (0 points: HR 5.56, 95% CI 5.27-7-5.87; 1 point: HR 1.31, 95% CI 1.25-1.33; 2 points: HR 0.75, 95% CI 0.74-0.76; 3 points: HR 1.13, 95% CI 1.11-1.15; 4 points, HR 0.61, 95% CI 0.61-0.62) compared to the original data.

conclusionBiomarkers are superior to clinical characteristics to study treatment heterogeneity in acute heart failure.

Indexed as

Acute DiseaseAgedBiomarkersDiureticsFemaleHeart FailureHumansMaleXanthinesBiomarkersDiureticsrolofyllineXanthinesAcute heart failureBiomarkersRolofyllineSubpopulation treatment effect pattern plotTreatment heterogeneity

Identifiers

PMID28656542
PMCPMC5550531
OpenAlexW2727323519

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.