Impact of Vutrisiran on Cardiac Biomarkers in Patients With Transthyretin Amyloidosis With Cardiomyopathy From HELIOS-B
Bibliographic record
Abstract
BACKGROUND: Before the development of disease-modifying therapies for transthyretin amyloidosis cardiomyopathy (ATTR-CM), N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and troponin I/T were recognized as independent prognostic biomarkers of mortality. This study evaluated the prognostic value of these biomarkers in a contemporary patient population and the impact of vutrisiran, an RNA interference therapeutic that rapidly knocks down circulating transthyretin, on biomarker levels. OBJECTIVES: This study sought to evaluate the association between risk of cardiovascular events and all-cause mortality with baseline NT-proBNP and troponin I levels and changes from baseline at month 6 in patients from HELIOS-B and explore how vutrisiran impacts biomarkers over time. METHODS: In HELIOS-B, a double-blind, placebo-controlled study, 655 patients with ATTR-CM were randomized 1:1 to receive vutrisiran or placebo for up to 36 months. The primary endpoint was a composite outcome of all-cause mortality and recurrent cardiovascular events. All-cause mortality through 42 months was a secondary endpoint. NT-proBNP and troponin I were assessed as prespecified exploratory endpoints. RESULTS: Baseline NT-proBNP and troponin I levels were independently associated with risks of the composite outcome and all-cause mortality (P < 0.0001 for both biomarkers and endpoints). At month 6, increases in NT-proBNP from baseline were associated with higher risk of the composite outcome and all-cause mortality, and decreases in troponin I were associated with a lower risk of the composite outcome. At month 30, the median changes from baseline of NT-proBNP and troponin I were 753 pg/mL (Q1-Q3: -8 to 2,573 pg/mL) and 9.7 pg/mL (Q1-Q3: -6.3 to 41.2 pg/mL) in the placebo arm and 118 pg/mL (Q1-Q3: -419 to 911 pg/mL) and -5.8 pg/mL (Q1-Q3: -25.0 to 10.0 pg/mL) in the vutrisiran arm. The geometric mean fold-change ratios (vutrisiran/placebo) were 0.68 (95% CI: 0.61-0.76) for NT-proBNP and 0.68 (95% CI: 0.62-0.75) for troponin I (P < 0.0001 for both). CONCLUSIONS: Patterns of associations between biomarkers and adverse outcomes support the importance of early treatment initiation and the potential for risk reduction in patients with ATTR-CM. Vutrisiran maintained stable or reduced levels of both biomarkers consistent with the benefit of treatment in reducing the risk of cardiovascular events and all-cause mortality. (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149).
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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 | 0.001 | 0.001 |
| 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".