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

2019· article· en· W2956532717 on OpenAlexafffund
Kenneth W. Mahaffey, Meg Jardine, Séverine Bompoint, Christopher P. Cannon, Bruce Neal, Hiddo J.L. Heerspink, David M. Charytan, Robert Edwards, Rajiv Agarwal, George L. Bakris, Scott Bull, George Capuano, Dick de Zeeuw, Tom Greene, Adeera Levin, Carol A. Pollock, Tao Sun, David C. Wheeler, Yshai Yavin, Hong Zhang, Bernard Zinman, Norman Rosenthal, Barry M. Brenner, Vlado Perkovic

Bibliographic record

VenueCirculation · 2019
Typearticle
Languageen
FieldMedicine
TopicDiabetes Treatment and Management
Canadian institutionsLunenfeld-Tanenbaum Research InstituteUniversity of British Columbia
FundersMerck Sharp and DohmeUniversity of California, San FranciscoAstellas PharmaEisaiNxStageMedical Research CouncilVerily Life SciencesNational Health and Medical Research CouncilAstraZenecaAmarin CorporationNational Institutes of HealthRegeneron PharmaceuticalsPfizerInnovent BiologicsJanssen PharmaceuticalsAblynxUniversity of WashingtonIronwood Pharmaceuticals, IncorporatedRelypsaUniversity of ChicagoAlnylam PharmaceuticalsNovo NordiskMyoKardiaDaiichi Sankyo EuropeServierGilead SciencesGeorge Institute for Global HealthKidney Foundation of CanadaKowa CompanyNational Institute of Diabetes and Digestive and Kidney DiseasesSanofiGlaxoSmithKlineAmgenCelgeneEli Lilly and CompanyAkebia TherapeuticsBristol-Myers Squibb
KeywordsMedicineCanagliflozinDiabetes mellitusKidney diseaseInternal medicineHazard ratioMyocardial infarctionStroke (engine)Type 2 diabetesHeart failureType 2 Diabetes MellitusEndocrinologyConfidence interval

Abstract

fetched live from OpenAlex

BACKGROUND: Canagliflozin 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). METHODS: In 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. RESULTS: Primary 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). CONCLUSIONS: Canagliflozin 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 REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02065791.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.072
Threshold uncertainty score0.571

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.007
GPT teacher head0.208
Teacher spread0.201 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations288
Published2019
Admission routes2
Has abstractyes

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