Publications

The material below is provided to support scientific exchange. Any content about investigational therapeutics or investigational uses of locally approved products does not establish the safety or efficacy of these therapeutics or uses, and there is no guarantee of local regulatory approval.

For questions beyond a product’s authorized indications or for information not available here, please contact Alnylam Medical Information.

Influence of Disease-Modifying Therapy on the Efficacy of Vutrisiran in Transthyretin Cardiac Amyloidosis

Publication Details

Journal of the American College of Cardiology

August 2026

Access Here

Author(s)

Arielle Abovich ¹, Marianna Fontana ², Brian Claggett ¹, Julian D Gillmore ², Francesco Cappelli ³, Amrut V Ambardekar ⁴, Caroline Morbach ⁵, Pablo Garcia-Pavia ⁶, Ronald M Witteles ⁷, Mathew S Maurer ⁸, Patrick Y Jay ⁹, Alisa Kosheleff ⁹, Sameer Bansilal ⁹, Scott D Solomon ¹⁰

Affiliations

¹Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; ²National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital, London, United Kingdom; ³Bis Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy; Tuscan Amyloidosis Referral Center Careggi University Hospital, Florence, Italy; ⁴Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; ⁵Department of Clinical Research and Epidemiology, Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany; Department of Medicine I, University Hospital Würzburg, Würzburg, Germany; ⁶Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Health Research Institute of the Puerta de Hierro Majadahonda-Segovia de Arana, Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBER-CV), and Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; ⁷Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA; ⁸Columbia University Irving Medical Center, New York, New York, USA; ⁹Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA; ¹⁰Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

Abstract

Background

Vutrisiran, an RNA interference therapeutic, reduced all-cause mortality and recurrent cardiovascular events in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) in the HELIOS-B trial. Whether concomitant disease-modifying or heart failure therapy modifies the efficacy of vutrisiran has not been described.

Objective

We aimed to characterize patterns of concomitant therapy use in HELIOS-B, describe medication initiation rates by treatment arm, and evaluate whether concomitant therapy modified vutrisiran’s treatment effect.

Methods

In HELIOS-B, 654 randomized patients with ATTR-CM received vutrisiran or placebo. We assessed baseline use and postrandomization initiation of tafamidis, sodium-glucose cotransporter-2 (SGLT2) inhibitors, mineralocorticoid receptor antagonists (MRA), beta-blockers, and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors), and used time-updated Lin-Wei-Yang-Ying models to evaluate treatment effect modification on the primary composite endpoint of all-cause mortality and recurrent cardiovascular events.

Results

At baseline, 40% of participants were receiving tafamidis and 77% at least 1 heart failure medication. MRAs and SGLT2 inhibitors were the most frequently initiated therapies during follow-up, with initiation rates numerically higher across all heart failure medication classes in the placebo group. There was no statistically significant evidence that the treatment effect of vutrisiran was modified by baseline or time-updated use of any medication class (P-interaction: tafamidis 0.95, SGLT2 inhibitors 0.59, MRA 0.92, beta-blockers 0.75, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors 0.82).

Conclusions

In HELIOS-B, there was no statistically significant evidence that the treatment benefit of vutrisiran on all-cause mortality and recurrent cardiovascular events was modified by concomitant use of tafamidis or heart failure therapies. These findings support the consistency of vutrisiran’s efficacy across the spectrum of contemporary ATTR-CM pharmacotherapy. (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149)