Evidence map›SGLT2 inhibitors × cardiovascular events›PMID 31291786›Full record

Trial reportCirculation2019

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups.

Kenneth W Mahaffey, Meg J Jardine, Severine Bompoint, Christopher P Cannon, Bruce Neal, Hiddo J L Heerspink, David M Charytan, Robert Edwards, Rajiv Agarwal, George Bakris and 14 more

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

Trial report in Circulation, 2019. The graph read 3 numbers from its abstract, feeding 1 cell of the map, but it casts no vote: it is a later paper about NCT02065791, whose primary report (PMID 30990260) speaks for the trial. It reports registered trial NCT02065791. Cited by 129 papers, 24 of them syntheses that pooled it.

3numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed, 24 pooled it
32.7field-weighted citation impact, top 1% 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 →
0.51 · no effect
Cardiovascular eventsno clear difference · head-to-head · ascvd, t2dfeeds one cell of the map
HR 0.850.69 to 1.06
Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25).
FeedsSGLT2 inhibitors×cardiovascular events
Cardiovascular eventsfavours the treatment · head-to-head · ascvd, t2dfeeds one cell of the map
HR 0.680.49 to 0.94
Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25).
FeedsSGLT2 inhibitors×cardiovascular events
Cardiovascular eventsfavours the treatment · head-to-head · ascvd, t2dfeeds one cell of the map
HR 0.800.67 to 0.95P=0.01
Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25).
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

No readable resultOpen 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 resultNCT02065791 · 4,401 enrolled · 2014
HR 0.700.59 to 0.82
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
NCT019897545,813 enrolled · 2014
HR 0.720.55 to 0.94
NCT010326294,330 enrolled · 2009
HR 0.930.78 to 1.12
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
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.

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
NCT04450576 unknown statusnot on this map

HbA1c as an Early Serologic Marker for the Hemodynamic Progression of Stage A Heart

TypeobservationalSponsorParkview Medical CenterRan2019 to 2020Enrolled200ConditionsHeart Failure, DiastolicArmsGlycosylated hemoglobin
5 · Its place in the literature

Who cites it

129 citing papers in PubMed, 24 syntheses or guidelines pooled it, 284 citations in OpenAlex.

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  10. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022
    Guideline
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69 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

  • Commented on by
    2020
7 · Who and what money

Authors and funding

24 authors at 2 institutions in 3 countries.

Kenneth W MahaffeyStanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, CA (K.W.M.).
Meg J JardineGeorge Institute for Global Health, University of New South Wales, Sydney, Australia (M.J.J., S.B., B.N., H.J.L.H., V.P.).
Severine BompointGeorge Institute for Global Health, University of New South Wales, Sydney, Australia (M.J.J., S.B., B.N., H.J.L.H., V.P.).
Christopher P CannonCardiovascular Division, Brigham & Women's Hospital, Boston, MA (C.P.C.).
Bruce NealGeorge Institute for Global Health, University of New South Wales, Sydney, Australia (M.J.J., S.B., B.N., H.J.L.H., V.P.).
Hiddo J L HeerspinkGeorge Institute for Global Health, University of New South Wales, Sydney, Australia (M.J.J., S.B., B.N., H.J.L.H., V.P.).
David M CharytanNephrology Division, NYU School of Medicine and NYU Langone Medical Center, New York (D.M.C.).
Robert EdwardsJanssen Research & Development, LLC, Raritan, NJ (R.E., S.B., G.C., T.S., Y.Y., N.R.).
Rajiv AgarwalIndiana University School of Medicine and VA Medical Center, Indianapolis (R.A.).
George BakrisDepartment of Medicine, University of Chicago Medicine, IL (G.B.).
Scott BullJanssen Research & Development, LLC, Raritan, NJ (R.E., S.B., G.C., T.S., Y.Y., N.R.).
George CapuanoJanssen Research & Development, LLC, Raritan, NJ (R.E., S.B., G.C., T.S., Y.Y., N.R.).
Dick de ZeeuwDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, The Netherlands (H.J.L.H., D.d.Z.).
Tom GreeneDivision of Biostatistics, Department of Population Health Sciences, University of Utah, Salt Lake City (T.G.).
Adeera LevinDivision of Nephrology, University of British Columbia, Vancouver, Canada (A.L.).
Carol PollockKolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW, Australia (C.P.).
Tao SunJanssen Research & Development, LLC, Raritan, NJ (R.E., S.B., G.C., T.S., Y.Y., N.R.).
David C WheelerDepartment of Renal Medicine, UCL Medical School, London, UK (D.C.W.).
Yshai YavinJanssen Research & Development, LLC, Raritan, NJ (R.E., S.B., G.C., T.S., Y.Y., N.R.).
Hong ZhangRenal Division of Peking University First Hospital, Beijing, China (H.Z.).
Bernard ZinmanLunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, ON, Canada (B.Z.).
Norman RosenthalJanssen Research & Development, LLC, Raritan, NJ (R.E., S.B., G.C., T.S., Y.Y., N.R.).
Barry M BrennerBaim Institute for Clinical Research, Boston, MA (D.M.C., C.P.C., B.M.B.).
Vlado PerkovicGeorge Institute for Global Health, University of New South Wales, Sydney, Australia (M.J.J., S.B., B.N., H.J.L.H., V.P.).
Stanford University · USUniversity of Sydney · AU

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 reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention).

methodsIn CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care.

resultsPrimary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome).

conclusionsCanagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease. CLINICAL

trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT02065791.

Indexed as

CanagliflozinCardiovascular DiseasesDiabetes Mellitus, Type 2Double-Blind MethodFemaleHumansKidney Failure, ChronicMaleMiddle AgedPlacebo EffectProportional Hazards ModelsRenal Insufficiency, ChronicRiskSecondary PreventionSodium-Glucose Transporter 2 InhibitorsTreatment OutcomeCanagliflozinSodium-Glucose Transporter 2 Inhibitorscanagliflozinclinical trialdiabetes mellitusprimary preventionrenal insufficiency, chronicsecondary prevention

Identifiers

PMID31291786
PMCPMC6727954
OpenAlexW2956532717

What OpenQuestion holds

Texttitle and abstract
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.