Dapagliflozin reduces uric acid concentration, an independent predictor of adverse outcomes in <scp>DAPA‐HF</scp>
Bibliographic record
Abstract
Aims Blood uric acid (UA) levels are frequently elevated in patients with heart failure and reduced ejection fraction (HFrEF), may lead to gout and are associated with worse outcomes. Reduction in UA is desirable in HFrEF and sodium–glucose cotransporter 2 inhibitors may have this effect. We aimed to examine the association between UA and outcomes, the effect of dapagliflozin according to baseline UA level, and the effect of dapagliflozin on UA in patients with HFrEF in the DAPA‐HF trial. Methods and results The association between UA and the primary composite outcome of cardiovascular death or worsening heart failure, its components, and all‐cause mortality was examined using Cox regression analyses among 3119 patients using tertiles of UA, after adjustment for other prognostic variables. Change in UA from baseline over 12 months was also evaluated. Patients in tertile 3 (UA ≥6.8 mg/dl) versus tertile 1 (<5.4 mg/dl) were younger (66.3 ± 10.8 vs. 68 ± 10.2 years), more often male (83.1% vs. 71.5%), had lower estimated glomerular filtration rate (58.2 ± 17.4 vs. 70.6 ± 18.7 ml/min/1.73 m 2 ), and more often treated with diuretics. Higher UA was associated with a greater risk of the primary outcome (adjusted hazard ratio tertile 3 vs. tertile 1: 1.32, 95% confidence interval [CI] 1.06–1.66; p = 0.01). The risk of heart failure hospitalization and cardiovascular death increased by 7% and 6%, respectively per 1 mg/dl unit increase of UA ( p = 0.04 and p = 0.07). Spline analysis revealed a linear increase in risk above a cut‐off UA value of 7.09 mg/dl. Compared with placebo, dapagliflozin reduced UA by 0.84 mg/dl (95% CI −0.93 to −0.74) over 12 months ( p < 0.001). Dapagliflozin improved outcomes, irrespective of baseline UA concentration. Conclusion Uric acid remains an independent predictor of worse outcomes in a well‐treated contemporary HFrEF population. Compared with placebo, dapagliflozin reduced UA and improved outcomes irrespective of UA concentration.
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How this classification was reachedexpand
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 | 0.002 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".