Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure with Reduced or Preserved Ejection Fraction: A Meta-Analysis
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Bibliographic record
Abstract
Abstract Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to be an effective therapy in improving heart failure outcomes. We conducted a meta-analysis of randomized controlled trials to evaluate the efficacy of SGLT2 inhibitors in heart failure patients with either a reduced or preserved ejection fraction. Methods and results We searched MEDLINE and EMBASE for large (≥1000 patients) randomized controlled trials evaluating the effects of SGLT2 inhibitors compared with placebo in the setting of heart failure until September 2021. Our primary outcome was the composite of heart failure hospitalization and cardiovascular death, and secondary outcomes included all-cause mortality and total heart failure hospitalizations. We pooled hazard ratios and risk ratios and evaluated risk of bias with the Cochrane Collaboration tool. Four randomized controlled trials (DAPA HF, EMPEROR-Preserved, EMPEROR-Reduced, and SOLOIST-WHF) were included (n = 15 684); two of which evaluated patients with a reduced LVEF, one of which evaluated patients with a preserved LVEF, and one of which included both. Treatment with SGLT2 inhibitors resulted in a significant reduction in the composite of CV death and heart failure hospitalization (HR: 0.76, 95% CI: 0.70, 0.82, I2: 0%, P < 0.00001). This was consistent in sub-groups of patients with LVEF ≤40% (n = 9199, HR: 0.74, 95% CI: 0.68, 0.81, I2: 0%) and LVEF >40% (n = 6482, HR: 0.78, 95% CI: 0.68, 0.89, I2: 0%, P-for-interaction: 0.57), as well as in sub-groups of patients with and without diabetes mellitus at baseline (P-for-interaction: 0.81). SGLT2 inhibitors were associated with a significant reduction in cardiovascular death (HR: 0.87, 95% CI: 0.79, 0.97, I2: 0%, P < 0.00001) and total heart failure hospitalization (RR: 0.71, 95% CI: 0.67, 0.76, I2: 0%, P < 0.00001); although a potential trend towards reduced all-cause mortality was noted with SGLT2 inhibitors, no statistically significant difference was observed (HR: 0.91, 95% CI: 0.83, 1.00, I2: 14%, P = 0.05). Conclusions Sodium-glucose cotransporter 2 inhibitors reduce cardiovascular death and heart failure hospitalization among patients with heart failure, regardless of LVEF status.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.003 |
| Bibliometrics | 0.001 | 0.004 |
| 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) | 0.016 | 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 it