Evidence map›Antihypertensives × cardiovascular events›PMID 39844714›Full record

Trial reportEuropean journal of heart failure2025

Canagliflozin reduces oral loop diuretic intensification in patients with type 2 diabetes: A participant-level pooled analysis of the CANVAS and CREDENCE trials.

Safia Chatur, Muthiah Vaduganathan, Robert A Fletcher, Vlado Perkovic, Hiddo Heerspink, Clare Arnott, Carol Pollock, Kenneth W Mahaffey, Bruce Neal, Meg Jardine and 2 more

2 registry-linked trialsAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European journal of heart failure, 2025. The graph read 1 number from its abstract, feeding 1 cell of the map, but it casts no vote: it is a later paper about NCT01032629, whose primary report (PMID 28605608) speaks for the trial. It reports registered trial NCT01032629. Cited by 2 papers.

1number the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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.

Read, but not usablea number the graph found but could not read as for or against

Cardiovascular eventscomparator not stated · t2d, heart_failurefeeds one cell of the map
HR 0.640.58 to 0.70
Inclusion of oral diuretic intensification in an expanded HF composite outcome inclusive of cardiovascular death and HF hospitalization approximately double the number of events, with similar observed treatment effect (HR 0.64; 95% CI 0.58-0.70).
FeedsAntihypertensives×cardiovascular events

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Antihypertensives×cardiovascular events

No readable resultOpen on the map →What to test next →

1 readable study in this cell: 1 favour the treatment, 0 find no difference, 0 favour the comparator.

Belief with this paper
0.50one trial · 1 family supports, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascu…PMID 27039945 · 12,705 enrolled · 2007
HR 0.710.56 to 0.90

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · 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.

NCT01032629 phase3completed

A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of JNJ-28431754 on Cardiovascular Outcomes in Adult Subjects With Type 2 Diabetes Mellitus

Ran2009Enrolled4,330Registered outcomes13Posted comparisons33ConditionsCardiovascular Diseases, Diabetes Mellitus, Type 2, Risk FactorsArmsCanagliflozin (JNJ-28431754) 100 mg, Canagliflozin (JNJ-28431754) 300 mg, Placebo
Open the trial in the graph
NCT02065791 phase3completed

A Randomized, Double-blind, Event-driven, Placebo-controlled, Multicenter Study of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Subjects With Type 2 Diabetes Mellitus and Diabetic Nephropathy

Ran2014Enrolled4,401Registered outcomes8Posted comparisons8ConditionsDiabetes Mellitus, Type 2, Diabetic NephropathyArmsCanagliflozin, Placebo
Open the trial in the graph
5 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
6 · The record

Corrections and comments

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

7 · Who and what money

Authors and funding

12 authors.

Safia ChaturCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Muthiah VaduganathanCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Robert A FletcherThe George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Vlado PerkovicThe George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Hiddo HeerspinkPharmacy and Pharmacology, University of Groningen, Groningen, The Netherlands.
Clare ArnottThe George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Carol PollockKolling Institute of Medical Research, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
Kenneth W MahaffeyStanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA, USA.
Bruce NealThe George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Meg JardineNHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
Scott D SolomonCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Brendon L NeuenThe George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.

Funding

Janssen Research and DevelopmentMenarini Group
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

aimsThe sodium-glucose cotransporter 2 inhibitor canagliflozin reduces the risk of heart failure (HF) hospitalization or cardiovascular death and chronic kidney disease (CKD) progression among patients with type 2 diabetes at high cardiovascular risk or with CKD. Patients with type 2 diabetes commonly have coexisting HF or CKD that require treatment with loop diuretics; however, the prognostic implications of oral loop diuretic intensification are not well characterized. METHODS AND

resultsIn this participant-level pooled analysis of the CREDENCE and CANVAS trials (not including CANVAS-R), 1454/8731 (16.7%) patients were treated with loop diuretics at baseline. Over a median on-treatment follow-up of 2.2 years, 1264 patients (14.5%) required oral loop diuretic intensification, of whom 981 (77.6%) required initiation of oral loop diuretics and 283 (22.4%) required oral loop diuretic dose increase. Patients requiring oral loop diuretic intensification experienced rates of subsequent HF hospitalization, CKD progression and mortality that were 29.5-, 5.0-, and 3.5-fold higher, respectively, than those not requiring oral loop diuretic intensification. Treatment with canagliflozin reduced the need for oral loop diuretic intensification by 41% (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.53-0.66) including both new diuretic initiation (HR 0.65; 95% CI 0.57-0.74) and diuretic dose increase (HR 0.42; 95% CI 0.33-0.54). Inclusion of oral diuretic intensification in an expanded HF composite outcome inclusive of cardiovascular death and HF hospitalization approximately double the number of events, with similar observed treatment effect (HR 0.64; 95% CI 0.58-0.70).

conclusionAmong high-risk patients with type 2 diabetes, new oral loop diuretic intensification was frequent and portended adverse prognostic significance. Treatment with canagliflozin significantly reduced the need for loop diuretic intensification. CLINICAL

trial registrationCANVAS (Canagliflozin Cardiovascular Assessment Study), ClinicalTrials.gov NCT01032629; CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation), ClinicalTrials.gov NCT02065791.

Indexed as

CanagliflozinDiabetes Mellitus, Type 2Heart FailureRenal Insufficiency, ChronicSodium-Glucose Transporter 2 InhibitorsSodium Potassium Chloride Symporter InhibitorsAdministration, OralAgedDisease ProgressionFemaleFollow-Up StudiesHospitalizationHumansMaleMiddle AgedTreatment OutcomeCanagliflozinSodium-Glucose Transporter 2 InhibitorsSodium Potassium Chloride Symporter InhibitorsChronic kidney diseaseHeart failureLoop diureticType 2 diabetes

Identifiers

PMID39844714
PMCPMC12260334

What OpenQuestion holds

Texttitle and abstract
LicenceCC BY-NC-ND
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.