Time to Cardiovascular Benefits of Empagliflozin: A <i>Post Hoc</i> Observation from the EMPA-REG OUTCOME Trial
Why this work is in the frame
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Bibliographic record
Abstract
AIMS: In the EMPA-REG OUTCOME trial, in patients with type 2 diabetes and established atherosclerotic cardiovascular (CV) disease, empagliflozin vs. placebo reduced the risk of hospitalization for heart failure (HHF) by 35%, CV death/HHF by 34%, and CV death by 38%, with an early separation of the cumulative incidence curves. We explored at what time point after randomization these benefits became apparent. METHODS AND RESULTS: We expressed time trajectories for the effect of pooled empagliflozin doses vs. placebo on HHF, CV death/HHF, and CV death based on hazard ratios (95% confidence interval) and calculated the hazard ratio on the day the effect reached significance using Cox proportional hazards models. Overall, 7020 patients aged ≥18 years were treated with empagliflozin 10 mg (N = 2345), empagliflozin 25 mg (N = 2342), or placebo (N = 2333) once daily in addition to standard of care. Mean age (years ± SD) was 63.1 ± 8.6, and 72% were male. The benefit of empagliflozin on CV death first reached statistical significance on Day 59 (HR [95% confidence interval]) (0.28 [0.08, 0.96], P = 0.0424) and was generally sustained throughout the trial (overall 0.62 [0.49, 0.77], P < 0.0001). Risk reduction with empagliflozin on HHF reached statistical significance on Day 17 (0.10 [0.01, 0.87], P = 0.0372) and was sustained throughout the study (overall 0.65 [0.50, 0.85], P = 0.0017). For the composite outcome of CV death or HHF, risk reduction with empagliflozin reached statistical significance on Day 27 (0.28 [0.08, 0.97], P = 0.0445) and was sustained throughout follow-up (overall 0.66 [0.55, 0.79], P < 0.0001). CONCLUSIONS: In EMPA-REG OUTCOME, the benefit of empagliflozin in reducing the risk of HHF, CV death/HHF, and CV death emerged within weeks after treatment initiation. The earliest benefit appears to be on HHF.
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Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it