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Dapagliflozin in Patients Hospitalized for Heart Failure: Primary Results of the DAPA ACT HF-TIMI 68 Randomized Clinical Trial and Meta-Analysis of Sodium-Glucose Cotransporter-2 Inhibitors in Patients Hospitalized for Heart Failure

2025· article· en· W4413840361 on OpenAlexafffund
David D. Berg, Siddharth M. Patel, Paul M. Haller, Abby L. Cange, Michael G. Palazzolo, Andrea Bellavia, Julia Kuder, Akshay S. Desai, Silvio E. Inzucchi, John J.V. McMurray, Eileen O’Meara, Subodh Verma, Jan Bělohlávek, Jarosław Dróżdż, Béla Merkely, Modele O. Ogunniyi, T. Drasnar, Joseph L. Izzo, Balázs Sármán, John McGinty, Angel Mulkay, Andrzej Przybylski, Christian T. Ruff, Michelle L. O’Donoghue, Sabina A. Murphy, Marc S. Sabatine, Stephen D. Wiviott

Bibliographic record

VenueCirculation · 2025
Typearticle
Languageen
FieldMedicine
TopicDiabetes Treatment and Management
Canadian institutionsUniversity of British ColumbiaSt. Michael's HospitalUniversité de MontréalSt. Paul's HospitalMontreal Heart Institute
FundersJanssen Research and DevelopmentNational Heart, Lung, and Blood InstituteCanadian Institutes of Health ResearchAmerican RegentIntas PharmaceuticalsInstitut de Cardiologie de MontréalDaiichi Sankyo EuropeServierDeutsche HerzstiftungNovo NordiskDaiichi-SankyoDeutsche ForschungsgemeinschaftMedicines CompanyARCA BiopharmaZora BiosciencesNational Center for Advancing Translational SciencesVerily Life SciencesAstraZenecaAmarin CorporationSanofiAbiomedIonis PharmaceuticalsNational Institutes of HealthRegeneron PharmaceuticalsDefense Acquisition Program AdministrationBoston Scientific CorporationAlnylam PharmaceuticalsDuke Clinical Research InstituteCytokineticsMedpaceBrigham and Women's HospitalKowa CompanyHLS TherapeuticsGlaxoSmithKlineDeutsches Zentrum für Herz-KreislaufforschungHarvard CatalystUniversity of GlasgowiRhythm TechnologiesAmgenPfizerEli Lilly and Company
KeywordsDapagliflozinMedicineHeart failureTIMIRandomized controlled trialInternal medicineClinical trialCardiologyPharmacologyDiabetes mellitusEndocrinologyType 2 diabetesMyocardial infarction

Abstract

fetched live from OpenAlex

BACKGROUND: SGLT2 (sodium-glucose cotransporter-2) inhibitors reduce the risk of cardiovascular death or worsening heart failure (HF) in outpatients with HF. Data on initiation in patients hospitalized for HF are limited. METHODS: We conducted a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of in-hospital initiation of dapagliflozin (10 mg daily) in patients hospitalized for HF. The primary efficacy outcome was a composite of time to cardiovascular death or worsening HF through 2 months. Key safety outcomes included symptomatic hypotension and worsening kidney function. A prespecified meta-analysis of randomized trials evaluating initiation of SGLT2 inhibitors in patients hospitalized for HF was performed. RESULTS: Of 2401 patients (median age, 69 [Q1–Q3, 58–77] years, 815 [33.9%] women, 448 [18.7%] Black race, 1717 [71.5%] left ventricular ejection fraction ≤40%, 1074 [44.7%] newly diagnosed HF) randomized between September 2020 and March 2025, 1218 were assigned to dapagliflozin and 1183 to placebo. The primary outcome occurred in 133 patients (10.9%) in the dapagliflozin group and 150 (12.7%) in the placebo group (hazard ratio [HR], 0.86 [95% CI, 0.68–1.08]; P =0.20). A worsening HF event occurred in 115 (9.4%) and 122 (10.3%) patients in the dapagliflozin and placebo groups, respectively (HR, 0.91 [95% CI, 0.71–1.18]). Cardiovascular death occurred in 30 (2.5%) and 37 (3.1%) patients (HR, 0.78 [95% CI, 0.48–1.27]), and death from any cause occurred in 36 (3.0%) and 53 (4.5%) patients in the dapagliflozin and placebo groups, respectively (HR, 0.66 [95% CI, 0.43–1.00]). The rates of symptomatic hypotension were 3.6% and 2.2%, and the rates of worsening kidney function were 5.9% and 4.7% with dapagliflozin and placebo, respectively. In a meta-analysis of patients hospitalized for HF, SGLT2 inhibitors reduced the early risk of cardiovascular death or worsening HF (HR, 0.71 [95% CI, 0.54–0.93] P =0.012) and of all-cause death (HR, 0.57 [95% CI, 0.41–0.80]; P =0.001). CONCLUSIONS: In this trial, in-hospital initiation of dapagliflozin did not significantly reduce the risk of cardiovascular death or worsening HF through 2 months in hospitalized HF patients. However, the totality of randomized clinical trial data suggests that in-hospital initiation of SGLT2 inhibitors may reduce the early risk of cardiovascular death or worsening HF and of all-cause mortality. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04363697.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.009
metaresearch head score (Gemma)0.011
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.009
Threshold uncertainty score0.047

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0090.011
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0090.021
Bibliometrics0.0020.002
Science and technology studies0.0000.000
Scholarly communication0.0020.001
Open science0.0010.001
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0030.000

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 head0.023
GPT teacher head0.298
Teacher spread0.275 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designMeta-analysis
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

Citations35
Published2025
Admission routes2
Has abstractyes

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