Beneficial effects of vutrisiran on cardiac structure and function in ATTR-CM

In a secondary analysis of HELIOS-B, vutrisiran improved cardiac structure and function in patients with ATTR-CM compared with placebo.

This summary is based on the publication of Jering KS, Fontana M, Lairez O et al. - Effects of vutrisiran on cardiac structure and function in patients with transthyretin amyloidosis with cardiomyopathy: secondary outcomes of the HELIOS-B trial. Nat Med. 2025 Aug 6. [Online ahead of print] doi: 10.1038/s41591-025-03851-z.

Introduction and methods

Background

Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive disorder characterized by the accumulation of misfolded TTR protein in amyloid fibrils in the heart. In HELIOS-B, treatment with vutrisiran, a RNAi therapeutic agent that inhibits the production of TTR in the liver, reduced the risk of all-cause mortality or recurrent CV events compared with placebo in patients with ATTR-CM [1]. In addition, treatment with vutrisiran preserved functional capacity and quality of life (QoL) compared with placebo in patients with ATTR-CM [1].

Aim of the study

In a prespecified secondary analysis of HELIOS-B, the authors evaluated the effects of vutrisiran on echocardiographic measures of cardiac structure and function in patients with ATTR-CM.

Methods

The HELIOS-B trial was a global, placebo-controlled, double-blind, phase 3 RCT in which 654 patients with variant or wild-type ATTR-CM and a history of symptomatic HF were randomized to subcutaneous vutrisiran 25 mg or placebo every 12 weeks up to 36 months. Treatment with tafamidis was permitted. Serial echocardiograms were obtained at baseline and at 12, 18, 24 and 30 months.

Outcomes

Prespecified exploratory endpoints of HELIOS-B were the changes from baseline to 30 months in mean LV wall thickness and global longitudinal strain (GLS). Changes in other echocardiographic parameters were not predefined and were considered exploratory.

Main results

• At 30 months, vutrisiran attenuated the increase in LV wall thickness (LS mean difference: -0.4 mm; 95%CI: -0.8 to 0.0; P=0.03) and LV mass index (LS mean difference: -10.6 g m-2; 95%CI: -18.0 to -3.3; P<0.01) compared with placebo.
• Vutrisiran improved e’ velocity, E/A and E/e’ ratios compared with placebo (LS mean difference in lateral e’ velocity: 5.5 mm s-1; 95%CI: 2.4 to 8.5; P<0.01; E/A ratio: −0.3; 95%CI: −0.6 to 0.0; P=0.04; and average E/e’ ratio: −2.0; 95%CI: −2.9 to −1.2; P<0.01).
• Vutrisiran had no effect on LA volume index compared with placebo at 30 months (LS mean difference: −0.17 mm; 95%CI: −2.4 to 0.9; P=0.37).
• Compared with placebo, vutrisiran attenuated the decline in LVEF (LS mean difference: 2.0%; 95%CI: 0.3 to 3.7; P=0.02), absolute GLS (LS mean difference: 1.2%; 95%CI: 0.7 to 1.7; P<0.01), and LV stroke volume (LS mean difference: 4.1; 95%CI: 1.7 to 6.4; P<0.01) at 30 months.
• The treatment effects of vutrisiran compared with placebo on LV structure and diastolic and systolic function were similar or greater in the vutrisiran monotherapy population.

Conclusion

In this secondary analysis of HELIOS-B among patients with ATTR-CM, vutrisiran had beneficial effects on echocardiographic measures of cardiac structure and function including mean LV wall thickness, LV mass index, E/A and E/e’ ratios, GLS, LVEF and LV stroke volume.

Find this article online at Nat Med.

References

1. Fontana, M. et al. Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. N. Engl. J. Med. 392, 33–44 (2025).