Trial reportCardiovascular diabetology2021

Effects of canagliflozin on NT-proBNP stratified by left ventricular diastolic function in patients with type 2 diabetes and chronic heart failure: a sub analysis of the CANDLE trial.

Kenya Kusunose, Takumi Imai, Atsushi Tanaka, Kaoru Dohi, Kazuki Shiina, Takahisa Yamada, Keisuke Kida, Kazuo Eguchi, Hiroki Teragawa, Yasuchika Takeishi and 5 more

Open access · goldFull text readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Cardiovascular diabetology, 2021. The graph read 1 number from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. Cited by 13 papers, 3 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 3 pooled it
1.8field-weighted citation impact, top 14% 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.

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

Cardiac & vascular functiondescribes a change within one group, not a comparison · head-to-head · t2d, heart_failurefeeds one cell of the map
change 0.980.89 to 1.08
RESULTS: The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89-1.08) in the canagliflozin group and 1.07 (95% CI 0.97-1.18) in the glimepiride group.

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×cardiac & vascular function

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

12 readable studies in this cell: 6 favour the treatment, 6 find no difference, 0 favour the comparator.

Belief with this paper
0.50contested · 6 families support, 3 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT030579515,988 enrolled · 2017
Δ 1.320.45 to 2.19
NCT030579773,730 enrolled · 2017
Δ 2.060.16 to 3.96
NCT04252287476 enrolled · 2020
Δ 4.300.80 to 7.80
NCT03448406315 enrolled · 2018
Δ 4.00-5.00 to 13.0
NCT03448419312 enrolled · 2018
Δ -4.00-16.0 to 6.00
NCT0297347745 enrolled · 2017
Coefficient 0.01-0.23 to 0.25

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.

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

5 · Its place in the literature

Who cites it

13 citing papers in PubMed, 3 syntheses or guidelines pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Observational
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. 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

15 authors at 12 institutions in 1 country.

Kenya KusunoseDepartment of Cardiovascular Medicine, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima, Japan. kusunosek@tokushima-u.ac.jp.ORCID 0000-0002-4909-754X
Takumi ImaiDepartment of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan.
Atsushi TanakaDepartment of Cardiovascular Medicine, Saga University, Saga, Japan.
Kaoru DohiDepartment of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan.
Kazuki ShiinaDepartment of Cardiology, Tokyo Medical University, Tokyo, Japan.
Takahisa YamadaDevision of Cardiology, Osaka General Medical Center, Osaka, Japan.
Keisuke KidaDepartment of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Japan.
Kazuo EguchiDepartment of General Internal Medicine, Saitama Red Cross Hospital, Saitama, Japan.
Hiroki TeragawaDepartment of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima, Japan.
Yasuchika TakeishiDepartment of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.
Nobuyuki OhteDepartment of Cardiovascular Medicine, Nagoya City University East Medical Center, Nagoya, Japan.
Hirotsugu YamadaDepartment of Community Medicine for Cardiology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Masataka SataDepartment of Cardiovascular Medicine, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima, Japan.
Koichi NodeDepartment of Cardiovascular Medicine, Saga University, Saga, Japan.
CANDLE Trial Investigators
Saga University · JPTokushima University Hospital · JPFukushima Medical University · JPHiroshima General Hospital · JPMie University · JPNagoya City University · JPOsaka City University · JPOsaka Prefectural Medical Center · JPSaitama Red Cross Hospital · JPSt. Marianna University School of Medicine · JPTokushima University · JPTokyo Medical University · JP

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.

backgroundIdentification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline.

methodsPatients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function.

resultsThe change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89-1.08) in the canagliflozin group and 1.07 (95% CI 0.97-1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82-1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e') showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e' < 4.7 cm/s indicated there was an association with lower NT-proBNP levels in the canagliflozin group compared with that in the glimepiride group (ratio of change with canagliflozin/glimepiride (0.83, 95% CI 0.66-1.04).

conclusionsIn the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction.

Indexed as

AgedBiomarkersBlood GlucoseCanagliflozinDiabetes Mellitus, Type 2DiastoleFemaleHeart FailureHumansJapanMaleMiddle AgedNatriuretic Peptide, BrainPeptide FragmentsProspective StudiesSodium-Glucose Transporter 2 InhibitorsBiomarkersBlood GlucoseCanagliflozinNatriuretic Peptide, BrainPeptide Fragmentspro-brain natriuretic peptide (1-76)Sodium-Glucose Transporter 2 InhibitorsCanagliflozinDiastolic functionEchocardiographyNT-proBNPType 2 diabetes mellitus

Identifiers

PMID34521417
PMCPMC8442416
OpenAlexW3199771624

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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.