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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

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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)