Abstract 19363: Prevention of Progressive Worsening of Heart Failure Over Time With The Angiotensin-receptor Neprilysin Inhibitor Sacubitril/valsartan (lcz696)
Bibliographic record
Abstract
Background: The aim of this analysis was to examine the effect of the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696), compared with enalapril, on progressive worsening over time in patients with heart failure and reduced ejection fraction (HF-REF) enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidly in Heart Failure trial (PARADIGM-HF). Methods: In PARADIGM-HF, 4212 patients were randomized to enalapril and 4187 to sacubitril/valsartan. The primary outcome was the composite of cardiovascular (CV) death or hospitalization for heart failure (HF). To make a more comprehensive evaluation of HF worsening over time, we analysed the broader composite of CV death, HF hospitalization, emergency department visit for HF or intensification of therapy for HF (as time-to-first event) using the Kaplan-Meier (KM) method. Results: At baseline, 71% of patients were in NYHA functional class II and 24% in class III. Their mean LVEF was 27% and 93% were treated with a beta-blocker and 56% with a mineralocorticoid receptor antagonist. The median duration of follow-up was 27 months. The 1, 2 and 3 year KM rates for the composite outcome in the enalapril group were 16.5 (95% CI 15.5, 17.7)%, 27.6 (26.2, 29.1) and 34.8 (33.1-36.6)%, respectively. The corresponding rates in the sacubitril/valsartan group were 13.4 (12.4, 14.5), 22.1 (20.8, 23.4) and 29.5 (27.9, 31.2)%, respectively. Overall 1275 enalapril treated and 1038 sacubitril/valsartan treated patients had an event, giving a hazard ratio 0.79 (95% CI 0.73, 0.86), p<0.0001. Over the course of the trial, 55 fewer patients per 1000 treated with sacubitril/valsartan, compared with enalapril, experienced worsening (number needed to treat = 18). Conclusions: Even in patients with predominantly mild symptoms, well treated with evidence-based pharmacological therapy, worsening of HF over time was common, with more than a third of patients exhibiting progression within 3 years. The ARNI sacubitril/valsartan led to clinically important relative and absolute reductions in progressive worsening, compared with enalapril.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".