Evidence map›SGLT2 inhibitors × cardiovascular events›PMID 29526832›Full record

Trial reportCirculation2018

Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program.

Karin Rådholm, Gemma Figtree, Vlado Perkovic, Scott D Solomon, Kenneth W Mahaffey, Dick de Zeeuw, Greg Fulcher, Terrance D Barrett, Wayne Shaw, Mehul Desai and 2 more

4 registry-linked trialsFull text readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation, 2018. The graph read 5 numbers from its abstract, feeding 1 cell of the map: it supports the treatment in 1. It reports registered trial NCT01032629. Cited by 213 papers, 28 of them syntheses that pooled it.

5numbers the graph read from it
1cell of the map it votes in
213citing papers in PubMed, 28 pooled it
–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.

← favours the treatmentfavours the comparator →
0.51 · no effect
Cardiovascular eventsfavours the treatment · against placebo · t2d, heart_failurefeeds one cell of the map
HR 0.670.52 to 0.87
Overall, cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo (16.3 versus 20.8 per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.91), as was fatal or hospitalized HF (HR, 0.70; 95% CI, 0.55-0.89) and hospitalized HF alone (HR, 0.67; 95% CI, 0.52-0.87).
FeedsSGLT2 inhibitors×cardiovascular events
Cardiovascular eventsfavours the treatment · against placebo · t2d, heart_failurefeeds one cell of the map
HR 0.700.55 to 0.89
Overall, cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo (16.3 versus 20.8 per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.91), as was fatal or hospitalized HF (HR, 0.70; 95% CI, 0.55-0.89) and hospitalized HF alone (HR, 0.67; 95% CI, 0.52-0.87).
FeedsSGLT2 inhibitors×cardiovascular events
Cardiovascular eventsfavours the treatment · against placebo · t2d, heart_failurefeeds one cell of the map
HR 0.780.67 to 0.91
Overall, cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo (16.3 versus 20.8 per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.91), as was fatal or hospitalized HF (HR, 0.70; 95% CI, 0.55-0.89) and hospitalized HF alone (HR, 0.67; 95% CI, 0.52-0.87).
FeedsSGLT2 inhibitors×cardiovascular events

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 0.870.72 to 1.06
The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF (HR, 0.61; 95% CI, 0.46-0.80) compared with those without HF at baseline (HR, 0.87; 95% CI, 0.72-1.06; P interaction =0.021).
FeedsSGLT2 inhibitors×cardiovascular events
Cardiovascular eventscomparator not stated · t2d, heart_failurefeeds one cell of the map
HR 0.610.46 to 0.80
The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF (HR, 0.61; 95% CI, 0.46-0.80) compared with those without HF at baseline (HR, 0.87; 95% CI, 0.72-1.06; P interaction =0.021).
FeedsSGLT2 inhibitors×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.

SGLT2 inhibitors×cardiovascular events

SupportsOpen on the map →What to test next →

22 readable studies in this cell: 10 favour the treatment, 10 find no difference, 2 favour the comparator.

Belief with this paper
0.50contested · 9 families support, 6 contradict · against placebo
Without it
0.50This paper does not move the number.
← favours the treatmentfavours the comparator →
1 · no effect
This paper’s trial, registry resultNCT01989754 · 5,813 enrolled · 2014
HR 0.720.55 to 0.94
This paper4,330 enrolled · 2009
HR 0.780.67 to 0.91
NCT0546531762,197 enrolled · 2022
HR 0.750.65 to 0.86
NCT0399313226,774 enrolled · 2018
HR 1.010.91 to 1.11
NCT0173053417,190 enrolled · 2013
HR 0.930.84 to 1.03
NCT0493781616,746 enrolled · 2021
HR 1.000.83 to 1.20
NCT045096746,522 enrolled · 2020
HR 0.900.76 to 1.06
NCT036192136,263 enrolled · 2018
HR 0.820.73 to 0.92
NCT030579515,988 enrolled · 2017
HR 0.790.69 to 0.90
NCT020657914,401 enrolled · 2014
HR 0.700.59 to 0.82
NCT045647424,017 enrolled · 2020
Win Ratio (WR) 1.341.20 to 1.50
NCT030579773,730 enrolled · 2017
HR 0.750.65 to 0.86
NCT043636972,401 enrolled · 2020
HR 0.860.68 to 1.08
NCT04157751530 enrolled · 2020
Stratified Win Ratio 1.361.09 to 1.68
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
NCT01989754 phase4completed

A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects With Type 2 Diabetes Mellitus

Ran2014Enrolled5,813Registered outcomes3Posted comparisons3ConditionsAlbuminuria, Diabetes Mellitus, Type 2ArmsCanagliflozin, 100 mg, Canagliflozin, 300 mg, Placebo
Open the trial in the graph
NCT05719714 phase1 / phase2active not recruitingstarted 2024, after this paper: background citation

Effect of Dapagliflozin on Metabolomics and Cardiac Mechanics in Chronic Kidney Disease

Ran2024Enrolled18Registered outcomes5Posted comparisons0ConditionsChronic Kidney Diseases, Heart Failure, Heart Failure With Preserved Ejection Fraction, Kidney DiseasesArmsDapagliflozin 10 MG [Farxiga]
PMID 29166232PMID 29133604PMID 29762782PMID 10716471PMID 15504931PMID 16461840PMID 18760751PMID 21262990PMID 21817129PMID 24218128PMID 25370599PMID 25533966other papers from this trial
Open the trial in the graph
NCT05741658 phase4completedstarted 2023, after this paper: background citation

An Open-Label, Non-randomized, Multi-center Pilot Study to Evaluate the Safety and Efficacy of 4-week, Daily Oral Use of Dapagliflozin 10mg Tablet in Adults With a Fontan Circulation

Ran2023Enrolled29Registered outcomes8Posted comparisons0ConditionsHeart FailureArmsDapagliflozin 10mg Tab
PMID 28605608PMID 30882240PMID 3529918PMID 33189798PMID 32434052PMID 32419592PMID 32410463PMID 31916329PMID 31535829PMID 31256636PMID 30377261PMID 26378978other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

213 citing papers in PubMed, 28 syntheses or guidelines pooled it.

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

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

12 authors.

Karin RådholmDepartment of Medicine and Health Sciences, Division of Community Medicine, Primary Care, Faculty of Health Sciences, Department of Local Care West, County Council of Ötergötland, Linköping University, Sweden (K.R.).
Gemma Figtree
Vlado PerkovicThe George Institute for Global Health (K.R., V.P., B.N.).
Scott D SolomonUniversity of Sydney, Australia. Harvard Medical School and Brigham and Women's Hospital, Boston, MA (S.D.S.).
Kenneth W MahaffeyDepartment of Medicine, Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.).
Dick de ZeeuwUniversity of Groningen, University Medical Center Groningen, The Netherlands (D.d.Z.).
Greg FulcherUniversity of New South Wales, Sydney, Australia. Royal North Shore Hospital (G.F., V.P., G.F.).
Terrance D BarrettJanssen Research & Development, LLC, Raritan, NJ (T.D.B., W.S., M.D.).
Wayne ShawJanssen Research & Development, LLC, Raritan, NJ (T.D.B., W.S., M.D.).
Mehul DesaiJanssen Research & Development, LLC, Raritan, NJ (T.D.B., W.S., M.D.).
David R MatthewsOxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, United Kingdom (D.R.M).
Bruce NealThe George Institute for Global Health (K.R., V.P., B.N.).

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

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

backgroundCanagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure (HF) and cardiovascular death overall, in those with and without a baseline history of HF, and in other participant subgroups.

methodsThe CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomly assigned to canagliflozin or placebo and followed for a mean of 188 weeks. The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF.

resultsParticipants with a history of HF at baseline (14.4%) were more frequently women, white, and hypertensive and had a history of prior cardiovascular disease (all P<0.001). Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system, diuretics, and β-blockers at baseline (all P<0.001). Overall, cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo (16.3 versus 20.8 per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.91), as was fatal or hospitalized HF (HR, 0.70; 95% CI, 0.55-0.89) and hospitalized HF alone (HR, 0.67; 95% CI, 0.52-0.87). The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF (HR, 0.61; 95% CI, 0.46-0.80) compared with those without HF at baseline (HR, 0.87; 95% CI, 0.72-1.06; P interaction =0.021). The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline (all interaction P values >0.130), except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF ( P=0.03).

conclusionsIn patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease, canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups. Benefits may be greater in those with a history of HF at baseline. CLINICAL

trial registrationURL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629 and NCT01989754.

Indexed as

AgedBiomarkersBlood GlucoseCanagliflozinCause of DeathDiabetes Mellitus, Type 2Disease ProgressionEuropeFemaleHeart FailureHospitalizationHumansMaleMiddle AgedRisk AssessmentRisk FactorsBiomarkersBlood GlucoseCanagliflozinSodium-Glucose Transporter 2 Inhibitorscanagliflozinheart failurerandomized trialSGLT2 inhibitortype 2 diabetes mellitus

Identifiers

PMID29526832
PMCPMC6075881

What Socratic holds

Textfull text, public
LicenceCC BY
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 Socratic graph.