Effects of Sacubitril/Valsartan According to Natriuretic Peptide Levels in Patients Enrolled in PARADIGM-HF and PARAGON-HF
Bibliographic record
Abstract
BACKGROUND: Recent trials of new heart failure (HF) treatments suggest the effect of therapy may vary by N-terminal pro-B type natriuretic peptide (NT-proBNP) level. OBJECTIVES: The authors examined the efficacy of sacubitril/valsartan according to NT-proBNP levels in patients with reduced, mildly reduced, and preserved left ventricular ejection fraction (LVEF) enrolled in PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting-Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) and PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Receptor Blockers Global Outcomes in HF with Preserved Ejection Fraction). METHODS: Individual patient data from PARADIGM-HF and PARAGON-HF were pooled and participants were divided into categories defined by quintiles of NT-proBNP level. The primary outcome examined was the composite of HF hospitalization or cardiovascular death. RESULTS: Among the 13,195 patients enrolled in both trials, 13,142 (99.6%) had a baseline NT-proBNP level measured. The rate of the primary outcome (per 100 person-years) increased with NT-proBNP levels: quintile 1, 5.9 (95% CI: 5.3-6.5); quintile 2, 7.5 (95% CI: 6.9-8.2); quintile 3, 9.0 (95% CI: 8.2-9.7); quintile 4, 12.0 (95% CI: 11.1-12.9); and quintile 5, 20.8 (95% CI: 19.6-22.2). The relative risk reduction in the primary outcome with sacubitril/valsartan was consistent across NT-proBNP levels: the HR in quintile 1 was 0.79 (95% CI: 0.65-0.96); quintile 2, 0.87 (95% CI: 0.72-1.04); quintile 3, 0.79 (95% CI: 0.66-0.93); quintile 4, 0.85 (95% CI: 0.73-0.99); and quintile 5, 0.86 (95% CI: 0.76-0.97; P for interaction = 0.86). The absolute risk reduction was greatest in NT-proBNP quintile 5; the number needed to treat for the primary outcome over the median follow-up of 31 months was 16 in quintile 5 vs 37 in quintile 1. CONCLUSIONS: The relative risk reductions with sacubitril/valsartan were consistent irrespective of NT-proBNP level in HF patients across the range of LVEF. Consequently, the absolute risk reductions were greatest in patients with higher NT-proBNP levels. (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting-Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial]; NCT01035255; and PARAGON-HF [Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Receptor Blockers Global Outcomes in HF with Preserved Ejection Fraction]; NCT01920711).
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.000 | 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".