Influence of ejection fraction on outcomes with sacubitril/valsartan in patients with worsening heart failure with EF>40%: The PARAGLIDE-HF Trial
Bibliographic record
Abstract
BACKGROUND: In the PARAGLIDE-HF trial, treatment with sacubitril/valsartan (Sac/Val) was associated with greater reduction in NT-proBNP than valsartan (Val) alone in patients stabilized after an episode of worsening heart failure (HF) with left ventricular ejection fraction (LVEF) >40%. Treatment effects were most apparent in the subgroup with LVEF below normal (≤60%). This prespecified analysis sought to compare the detailed treatment effects and adverse event profiles of Sac/Val vs Val in patients with LVEF ≤60% vs >60%. METHODS: Baseline demographics and clinical characteristics were compared between patients with baseline LVEF ≤60% vs >60%. Rates of recurrent composite events (adjudicated CV death, HF hospitalizations, and urgent HF visits) were compared between groups using a semi-parametric proportional rates model. These recurrent composite events were also analyzed across the continuous LVEF spectrum using restricted cubic splines. Incidence of adverse events were analyzed using a logistic regression model with LVEF ≤60% vs >60%, treatment arm, and in-hospital/out-of-hospital randomization as covariates. The interaction of LVEF category and treatment arm was assessed for all models RESULTS: Compared to those with LVEF >60%, patients with LVEF ≤60% were younger with lower NYHA class, but similar NT-proBNP values at baseline and similar co-morbidity burden. Among patients with LVEF ≤60%, those treated with Sac/Val experienced fewer recurrent composite events compared to those treated with Val (rate ratio 0.60 [95% CI: 0.37-0.99], P = .046); predominantly driven by HF hospitalizations. Patients with LVEF >60% treated with Sac/Val vs Val demonstrated similar rates of recurrent composite events (RR 1.46 [0.77-2.79], P = .24) (interaction P-value = .032). This was consistent with the continuous analysis in which patients treated with Sac/Val were significantly less likely to have events compared with patients with Val at LVEF values below 58%. Patients with LVEF >60% treated with Sac/Val experienced more symptomatic hypotension (OR 3.55 [95% CI: 1.35-9.37], P = .01) compared to those treated with Val, whereas rates of symptomatic hypotension were comparable across treatment groups in patients with LVEF ≤60% (OR 1.36 [0.79-2.32], P = .27, interaction P-value .09). CONCLUSIONS: Compared to treatment with Val in patients with worsening HF and LVEF >40%, treatment with Sac/Val is associated with greater clinical benefit in those with LVEF ≤60% than in those with LVEF >60%. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT03988634.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".