Maurer, MS; Berk, JL; Damy, T; Sheikh, FH; González-Costello, J; Morbach, C; Delgado, D; ... Fontana, M; + view all Maurer, MS; Berk, JL; Damy, T; Sheikh, FH; González-Costello, J; Morbach, C; Delgado, D; Bondue, A; Azevedo, O; Poulsen, SH; Jankowska, EA; Yang, L; Bender, S; Eraly, SA; Jay, PY; Vest, J; Fontana, M; - view fewer (2025) Impact of Vutrisiran on Cardiac Biomarkers in Patients With Transthyretin Amyloidosis With Cardiomyopathy From HELIOS-B. Journal of the American College of Cardiology , 86 (6) pp. 459-475. 10.1016/j.jacc.2025.04.055.

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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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