Impact of Vutrisiran on Cardiac Biomarkers in Patients With Transthyretin Amyloidosis With Cardiomyopathy From HELIOS-B
Publication Details
Journal of the American College of Cardiology
August 2025
Author(s)
Mathew S Maurer1, John L Berk2, Thibaud Damy3, Farooq H Sheikh4, José González-Costello5, Caroline Morbach6, Diego Delgado7, Antoine Bondue8, Olga Azevedo9, Steen H Poulsen10, Ewa A Jankowska11, Lili Yang12, Shaun Bender13, Satish A Eraly13, Patrick Y Jay13, John Vest13, Marianna Fontana14
Affiliations
1Columbia University Irving Medical Center, New York, New York, USA; 2Boston University School of Medicine, Boston, Massachusetts, USA; 3Referral Center for Cardiac Amyloidosis and Department of Cardiology, Hôpital Henri Mondor, APHP, Créteil, France; 4MedStar Heart and Vascular Institute, MedStar Health/Georgetown University School of Medicine, Washington, DC, USA; 5Department of Cardiology, Hospital Universitari de Bellvitge and IDIBELL, CIBER-CV, Universitat de Barcelona, Barcelona, Spain; 6Department of Clinical Research and Epidemiology, Comprehensive Heart Failure Centre & Department of Internal Medicine I, Cardiology, University Hospital Würzburg, Würzburg, Germany; 7Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; 8Department of Cardiology, Hôpital Universitaire de Bruxelles, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; 9Cardiology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal; 10Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; 11Department of Translational Cardiology and Clinical Registries, Institute of Heart Diseases, Wrocław Medical University, Wroclaw, Poland; Institute of Heart Diseases, University Hospital in Wrocław, Wroclaw, Poland; 12Institute of Heart Diseases, University Hospital in Wrocław, Wroclaw, Poland; 13Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA; 14National Amyloidosis Centre, University College London, Division of Medicine, Royal Free Hospital, London, United Kingdom
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)
PMID
40769675
DOI
10.1016/j.jacc.2025.04.055
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