Comprehensive Analysis of the Effects of Sacubitril/Valsartan According to Sex Among Patients With Heart Failure and Reduced Ejection Fraction in PARADIGM‐HF
Bibliographic record
Abstract
Background Women with heart failure (HF) ejection fraction appeared to respond more favorably to sacubitril/valsartan, compared with valsartan, than men in PARAGON‐HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), driven by a greater reduction in total (first and recurrent) HF hospitalizations. Sex‐specific efficacy and safety of sacubitril/valsartan in PARADIGM‐HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) remain unreported. Methods and Results This post hoc analysis of PARADIGM‐HF examined sex‐based outcomes in patients with HF and reduced ejection fraction randomized to sacubitril/valsartan or enalapril. The primary end point was a composite of cardiovascular death or HF hospitalization. Secondary and exploratory efficacy outcomes, biomarker changes, and safety outcomes were also assessed. Among 8399 participants, 1832 (21.8%) were women. Women were older, had worse New York Heart Association functional class and Kansas City Cardiomyopathy Questionnaire scores, more symptoms of HF, and lower estimated glomerular filtration rate, yet had lower rates of HF hospitalization (and other worsening of HF) and cardiovascular death than men. Compared with enalapril, sacubitril/valsartan reduced the risk of the primary end point to a similar extent in both sexes: hazard ratios, 0.76 (95% CI, 0.62–0.94) in women and 0.80 (95% CI, 0.73–0.89) in men ( P ‐interaction=0.62). Results were consistent for the individual components of the primary outcome. The rate ratio for total HF hospitalizations was 0.66 (95% CI, 0.48–0.89) in women and 0.80 (95% CI, 0.69–0.94) in men ( P ‐interaction=0.25). Randomized treatment discontinuation and adverse effects of interest were similar in women and men. Conclusions In PARADIGM‐HF, sacubitril/valsartan, compared with enalapril, reduced the risk of HF hospitalizations, death from cardiovascular causes, and death from any cause similarly in women and men with HF with reduced ejection fraction. In addition, sacubitril/valsartan was safe and well tolerated, irrespective of sex. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01035255.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".