Outcomes, Safety and Tolerability of Sacubitril-Valsartan over 3 years of Follow-up in Canadian Practice: Insights from the PARTHENON Registry
Bibliographic record
Abstract
Background: Experience with sacubitril-valsartan in real-world patients with heart failure and reduced ejection fraction (HFrEF) is congruent with findings from clinical trials. Detailed assessment of safety and clinical outcomes in the Canadian context is less well explored. Methods: The PAtient RegisTry assessing effectiveness and safety of HEart failure treatment with LCZ696 acrOss CaNada (PARTHENON) was a prospective, observational, multicentre study. Patients with HFrEF who were prescribed sacubitril-valsartan were recruited from 32 sites across Canada and followed for at least 3 years. The primary outcome was the association between baseline natriuretic peptide levels and the combined endpoint of all-cause mortality or all-cause hospitalization. Secondary outcomes included incidence of hypotension, hyperkalemia, and renal impairment. Additionally, observed all-cause mortality was compared with risk-model predicted mortality. Results: A total of 996 patients were enrolled in the registry; 19.1% discontinued the study early, and 10.8% died. No statistically significant association occurred between baseline natriuretic peptide levels and all-cause mortality or all-cause hospitalization (adjusted hazard ratio 1.04; 95% confidence interval: 0.91-1.20). Clinically relevant hypotension, hyperkalemia, and an increased creatinine level were observed in 24%, 4%, and 24%, respectively. The mean absolute change in left ventricular ejection fraction over 18 months was +8.2% +/- 10.8%. The observed 3-year mortality rate was lower than the 3-year mortality rate predicted by the Meta-Analysis Global Group in Chronic (MAGGIC) risk score (10.8%, vs 29% +/- 13.7%); observed survival was higher than the Seattle Heart Failure Model predicted survival (89.2%, vs 53.4% +/- 26.4%). Conclusions: The PARTHENON registry confirms the safety and tolerability of sacubitril-valsartan in patients with HFrEF in a real-world setting. The registry also demonstrated improvement in left ventricular ejection fraction, and a lower mortality rate, compared to the predicted mortality rate in this population.
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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 | 0.005 | 0.016 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.007 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".