Evidence mapPaperPMID 34854308Full record

Trial reportJournal of the American Heart Association2021

Association Between Circulating GDF-15 and Cardio-Renal Outcomes and Effect of Canagliflozin: Results From the CANVAS Trial.

Taha Sen, Jingwei Li, Brendon L Neuen, Clare Arnott, Bruce Neal, Vlado Perkovic, Kenneth W Mahaffey, Wayne Shaw, William Canovatchel, Michael K Hansen and 1 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal of the American Heart Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 3 pooled it
3.7field-weighted citation impact, top 6% 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

22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 32 citations in OpenAlex.

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  13. Plasma proteomics of acute tubular injury.Nature communications · 2024
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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

11 authors at 4 institutions in 3 countries.

Taha SenDepartment of Clinical Pharmacy and Pharmacology University of Groningen The Netherlands.
Jingwei LiThe George Institute for Global HealthUNSW Sydney Sydney Australia.
Brendon L NeuenThe George Institute for Global HealthUNSW Sydney Sydney Australia.ORCID 0000-0001-9276-8380
Clare ArnottThe George Institute for Global HealthUNSW Sydney Sydney Australia.
Bruce NealThe George Institute for Global HealthUNSW Sydney Sydney Australia.ORCID 0000-0002-0490-7465
Vlado PerkovicThe George Institute for Global HealthUNSW Sydney Sydney Australia.
Kenneth W MahaffeyDepartment of Medicine Stanford Center for Clinical Research Stanford University School of Medicine Stanford CA.
Wayne ShawJanssen Research & Development, LLC Raritan NJ.
William CanovatchelJanssen Global Services, LLC Raritan NJ.
Michael K HansenJanssen Research & Development, LLC Spring House PA.ORCID 0000-0002-0062-0520
Hiddo J L HeerspinkDepartment of Clinical Pharmacy and Pharmacology University of Groningen The Netherlands.ORCID 0000-0002-3126-3730
The George Institute for Global Health · AUJanssen (United States) · USUniversity of Groningen · NLStanford Medicine · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background Studies have suggested that sodium glucose co-transporter 2 inhibitors exert anti-inflammatory effects. We examined the association of baseline growth differentiation factor-15 (GDF-15), a marker of inflammation and cellular injury, with cardiovascular events, hospitalization for heart failure (HF), and kidney outcomes in patients with type 2 diabetes in the CANVAS (Canagliflozin Cardiovascular Assessment Study) and determined the effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on circulating GDF-15. Methods and Results The CANVAS trial randomized 4330 people with type 2 diabetes at high cardiovascular risk to canagliflozin or placebo. The association between baseline GDF-15 and cardiovascular (non-fatal myocardial infarction, non-fatal stroke, cardiovascular death), HF, and kidney (40% estimated glomerular filtration rate decline, end-stage kidney disease, renal death) outcomes was assessed using multivariable adjusted Cox regression models. During median follow-up of 6.1 years (N=3549 participants with available samples), 555 cardiovascular, 129 HF, and 137 kidney outcomes occurred. Each doubling in baseline GDF-15 was significantly associated with a higher risk of cardiovascular (hazard ratio [HR], 1.2; 95% CI, 1.0‒1.3), HF (HR, 1.5; 95% CI, 1.2‒2.0) and kidney (HR, 1.5; 95% CI, 1.2‒2.0) outcomes. Baseline GDF-15 did not modify canagliflozin's effect on cardiovascular, HF, and kidney outcomes. Canaglifozin treatment modestly lowered GDF-15 compared with placebo; however, GDF-15 did not mediate the protective effect of canagliflozin on cardiovascular, HF, or kidney outcomes. Conclusions In patients with type 2 diabetes at high cardiovascular risk, higher GDF-15 levels were associated with a higher risk of cardiovascular, HF, and kidney outcomes. Canagliflozin modestly lowered GDF-15, but GDF-15 reduction did not mediate the protective effect of canagliflozin.

Indexed as

CanagliflozinCardiovascular DiseasesDiabetes Mellitus, Type 2Growth Differentiation Factor 15Kidney DiseasesHeart FailureHospitalizationHumansRisk AssessmentTreatment OutcomeCanagliflozinGrowth Differentiation Factor 15canagliflozinGDF‐15renal and cardiovascular outcomesSGLT2 inhibitor

Identifiers

PMID34854308
PMCPMC9075362
OpenAlexW3216594541

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
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 Socratic graph.