Evidence map›SGLT2 inhibitors × cardiovascular events›PMID 30591006›Full record

Trial reportStroke2019

Canagliflozin and Stroke in Type 2 Diabetes Mellitus.

Zien Zhou, Richard I Lindley, Karin Rådholm, Bronwyn Jenkins, John Watson, Vlado Perkovic, Kenneth W Mahaffey, Dick de Zeeuw, Greg Fulcher, Wayne Shaw and 4 more

2 registry-linked trialsOpen access · hybridAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Stroke, 2019. 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 33 papers, 3 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 3 pooled it
5.4field-weighted citation impact, top 3% 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.

← favours the treatmentfavours the comparator →
1 · no effect
Cardiovascular eventsno clear difference · against placebo · t2d, ascvdfeeds one cell of the map
HR 0.870.69 to 1.09
There were 309 participants with stroke events during follow-up (123 had prior stroke or transient ischemic attack at baseline and 186 did not), at a rate of 7.93/1000 patient-years among those assigned canagliflozin and 9.62/1000 patient-years among placebo (hazard ratio, 0.87; 95% CI, 0.69-1.09).
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

Does not voteOpen on the map →What to test next →

22 readable studies in this cell: 9 favour the treatment, 11 find no difference, 2 favour the comparator.

Belief with this paper
0.50contested · 9 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← 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 paper’s trial, registry resultNCT01032629 · 4,330 enrolled · 2009
HR 0.930.78 to 1.12
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
5 · Its place in the literature

Who cites it

33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 73 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Article
  7. Sodium-glucose cotransporter 2 inhibitors and atherosclerosis.American journal of preventive cardiology · 2025
    Review
  8. Article
  9. Review
  10. Observational
  11. Review
  12. Observational
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
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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

14 authors at 9 institutions in 6 countries.

Zien ZhouFrom The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia (Z.Z., V.P., B.N.).
Richard I LindleyThe George Institute for Global Health and University of Sydney, Australia (R.I.L., K.R.).
Karin RådholmThe George Institute for Global Health and University of Sydney, Australia (R.I.L., K.R.).
Bronwyn JenkinsRoyal North Shore Hospital, St Leonards, Sydney, Australia (B.J.).
John WatsonFaculty of Medicine, University of New South Wales, Sydney, Australia (J.W., B.N.).
Vlado PerkovicFrom The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia (Z.Z., V.P., B.N.).
Kenneth W MahaffeyStanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, CA (K.W.M.).
Dick de ZeeuwUniversity of Groningen, University Medical Center Groningen, the Netherlands (D.d.Z.).
Greg FulcherThe Royal North Shore Hospital and University of Sydney, Australia (V.P., G.F.).
Wayne ShawJanssen Research & Development, LLC, Raritan, NJ (W.S., R.O., M.D.).
Richard OhJanssen Research & Development, LLC, Raritan, NJ (W.S., R.O., M.D.).
Mehul DesaiJanssen Research & Development, LLC, Raritan, NJ (W.S., R.O., M.D.).
David R MatthewsOxford Centre for Diabetes, Endocrinology and Metabolism and Harris Manchester College, University of Oxford, United Kingdom (D.R.M.).
Bruce NealFrom The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia (Z.Z., V.P., B.N.).
Janssen (United States) · USRoyal North Shore Hospital · AUUniversity of Sydney · AUUNSW Sydney · AUCenter for Clinical Research (United States) · USLinköping University · SEThe George Institute for Global Health · AUUniversity of Groningen · NLUniversity of Oxford · GB

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.

Background and Purpose- This study reports the detailed effects of canagliflozin on stroke, stroke subtypes, and vascular outcomes in participants with and without cerebrovascular disease (stroke or transient ischemic attack) at baseline from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program. Methods- The CANVAS Program, comprising 2 similarly designed and conducted clinical trials, randomly assigned 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk to canagliflozin or placebo. Its primary outcome was a composite of major adverse cardiovascular events. The main outcome of interest for this report was fatal or nonfatal stroke. Additional exploratory outcomes were stroke subtypes and other vascular outcomes defined according to standard criteria. Results- There were 1 958 (19%) participants with prior stroke or transient ischemic attack at baseline. These individuals were older, more frequently women, and had higher rates of heart failure, atrial fibrillation, and microvascular disease (all P<0.001) compared with those without such a history. There were 309 participants with stroke events during follow-up (123 had prior stroke or transient ischemic attack at baseline and 186 did not), at a rate of 7.93/1000 patient-years among those assigned canagliflozin and 9.62/1000 patient-years among placebo (hazard ratio, 0.87; 95% CI, 0.69-1.09). Analysis of stroke subtypes found no effect on ischemic stroke (n=253, hazard ratio, 0.95; 95% CI, 0.74-1.22), a significant reduction for hemorrhagic stroke (n=30, hazard ratio, 0.43; 95% CI, 0.20-0.89) and no effect on undetermined stroke (n=29, hazard ratio, 1.04; 95% CI, 0.48-2.22). Effects on other cardiovascular outcomes were comparable among participants with and without stroke or transient ischemic attack at baseline. Conclusions- There were too few events in the CANVAS Program to separately define the effects of canagliflozin on stroke, but benefit is more likely than harm. The observed possible protective effect for hemorrhagic stroke was based on small numbers but warrants further investigation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629 and NCT01989754.

Indexed as

Diabetes ComplicationsDiabetes Mellitus, Type 2StrokeAgedCanagliflozinFemaleFollow-Up StudiesHumansMaleMiddle AgedCanagliflozincanagliflozincardiovascular diseasesdiabetes mellitus, type 2ischemic attack, transientstroke

Identifiers

PMID30591006
PMCPMC6358191
OpenAlexW2908457468

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.