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Impact of Vutrisiran on Cardiac Biomarkers in Patients With Transthyretin Amyloidosis With Cardiomyopathy From HELIOS-B

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Název: Impact of Vutrisiran on Cardiac Biomarkers in Patients With Transthyretin Amyloidosis With Cardiomyopathy From HELIOS-B
Autoři: Mathew S. Maurer, John L. Berk, Thibaud Damy, Farooq H. Sheikh, José González-Costello, Caroline Morbach, Diego Delgado, Antoine Bondue, Olga Azevedo, Steen H. Poulsen, Ewa A. Jankowska, Lili Yang, Shaun Bender, Satish A. Eraly, Patrick Y. Jay, John Vest, Marianna Fontana
Zdroj: Maurer, M S, Berk, J L, Damy, T, Sheikh, F H, González-Costello, J, Morbach, C, Delgado, D, Bondue, A, Azevedo, O, Poulsen, S H, Jankowska, E A, Yang, L, Bender, S, Eraly, S A, Jay, P Y, Vest, J & Fontana, M 2025, 'Impact of Vutrisiran on Cardiac Biomarkers in Patients With Transthyretin Amyloidosis With Cardiomyopathy From HELIOS-B', Journal of the American College of Cardiology, vol. 86, no. 6, pp. 459-475. https://doi.org/10.1016/j.jacc.2025.04.055
Informace o vydavateli: Elsevier BV, 2025.
Rok vydání: 2025
Témata: Male, Cardiomyopathies/blood, N-terminal prohormone of B-type natriuretic peptide, amyloidosis, cardiac biomarkers, transthyretin amyloidosis cardiomyopathy, troponin I, Middle Aged, Prognosis, Amyloid Neuropathies, Familial/blood, Troponin I/blood, Double-Blind Method, RNAi Therapeutics/methods, Humans, Prealbumin, Female, Natriuretic Peptide, Brain/blood, Peptide Fragments/blood, Biomarkers/blood, Aged, Troponin T/blood
Popis: 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).
Druh dokumentu: Article
Jazyk: English
ISSN: 0735-1097
DOI: 10.1016/j.jacc.2025.04.055
Přístupová URL adresa: https://www.jacc.org/doi/10.1016/j.jacc.2025.04.055
https://doi.org/10.1016/j.jacc.2025.04.055
https://pure.au.dk/portal/en/publications/a87d11cc-5c01-40dd-9c79-cd677a6f6a6a
https://doi.org/10.1016/j.jacc.2025.04.055
Rights: CC BY NC ND
Přístupové číslo: edsair.doi.dedup.....fc40020e282b982e2ecd60539f7f1698
Databáze: OpenAIRE
Popis
Abstrakt: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).
ISSN:07351097
DOI:10.1016/j.jacc.2025.04.055