Vutrisiran preserves multiple aspects of health status in ATTR-CM

In a prespecified analysis of the HELIOS-B trial, vutrisiran was associated with less deterioration across most components of the 23-item KCCQ over 30 months compared with placebo in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).

This summary is based on the publication of Hamatani Y, Claggett BL, Vaduganathan M, et al. - Effect of vutrisiran on components of health status in transthyretin amyloidosis with cardiomyopathy: the HELIOS-B study. Eur J Heart Fail. 2026 Mar 29:xuag088 [Online ahead of print]. doi: 10.1093/ejhf/xuag088

Introduction and methods

Background

Transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal disease characterized by the deposition of amyloid fibrils, which consist of misfolded transthyretin (TTR) aggregates, in the myocardium. The disease also severely impacts patients’ health status, with high symptom burden, physical limitations, and poor quality of life (QoL) [1-5].

Recently, the HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy) trial demonstrated that treatment with vutrisiran, an siRNA that inhibits hepatic synthesis of amyloidogenic TTR protein, reduced the risk of all-cause mortality or recurrent CV events compared with placebo in ATTR-CM patients [6]. It also resulted in maintenance of overall health status, as assessed with the Overall Summary Score (OSS) of the 23-item KCCQ [7].

Although the aggregated KCCQ summary scores, such as the OSS, are useful for assessing overall health status [8], they lack detail when it comes to describing the severity and limitations of individual measures of health status. A comprehensive and clinically interpretable assessment of the impact of vutrisiran on the KCCQ-OSS and each of the 23 KCCQ components may inform clinicians and patients better about the expected treatment benefits.

Aim of the study

In a prespecified analysis of the HELIOS-B trial, the authors examined the effect of vutrisiran versus placebo on individual KCCQ components among ATTR-CM patients.

Methods

The HELIOS-B trial was a global, multicenter, placebo-controlled, double-blind, phase 3 RCT in which 654 patients (aged 18–85 years) with variant or wild-type ATTR-CM and a history of HF were randomized to subcutaneous vutrisiran 25 mg or placebo every 12 weeks up to 36 months. Treatment with tafamidis (either at baseline or initiated during the trial) was permitted. The KCCQ (range: 0 (worst) to 100 (best) points) was administered at randomization and every 6 months thereafter up to 30 months. KCCQ-OSS assessments at both baseline and 30 months were available for 486 participants.

Outcomes

The outcome measures were mean score changes in all 23 KCCQ components from baseline to 30 months and overall change in the KCCQ-OSS as a function of age.

Main results

Changes in KCCQ components

• At baseline, mean scores of the individual 23 KCCQ components were comparable between patients randomized to vutrisiran and those receiving placebo (total n=652).
• In the overall population, the mean scores of all KCCQ components declined in the placebo group from baseline to 30 months, except for the 2 items related to self-efficacy. In contrast, in the vutrisiran group, 5 of 23 components numerically improved, including 2 QoL items, both self-efficacy items and the 1 symptom-stability item.
• Vutrisiran treatment was associated with more favorable changes from baseline to 30 months in most KCCQ components compared with placebo (median placebo-corrected change: 3.8 points; range: –0.9 to 7.6).
• The greatest nominal differences in mean score change between the vutrisiran and placebo groups were observed for “hurrying or jogging” (difference: 7.6 points; 95%CI: 1.9–13.4), “walking 1 block on level ground” (difference: 7.0 points; 95%CI: 2.2–11.9), and “discouraged/down with HF” (difference: 6.8 points; 95%CI: 2.9–10.7).
• In general, greater improvements from baseline to 30 months with vutrisiran versus placebo were seen in domains related to QoL and physical limitations.
• In patients not on tafamidis at baseline (i.e., monotherapy population; n=270), similar or greater benefits of vutrisiran over placebo were observed, with the largest improvements seen in the domains physical limitations, social limitations, and QoL and the items related to frequency and burden of shortness of breath.
• Responder analyses showed that more vutrisiran-treated patients experienced improvement or maintenance of scores in 21 of the 23 KCCQ components from baseline to 30 months compared with the placebo group in both the overall and monotherapy populations.

Change in KCCQ-OSS as function of age

• The KCCQ-OSS at 30 months was inversely related to age. Vutrisiran treatment shifted the relationship between age and KCCQ-OSS at 30 months by 11 years (95%CI: 3–20), meaning that the KCCQ-OSS of vutrisiran-treated patients was similar to that of patients in the placebo arm who were 11 years younger.

Conclusion

In this prespecified analysis of the HELIOS-B trial, vutrisiran treatment was associated with improvements in most KCCQ components over 30 months compared with placebo in ATTR-CM patients, with the greatest benefits observed in the domains physical limitations and QoL. In patients not on tafamidis at baseline, similar or greater benefits of vutrisiran over placebo were found. The overall magnitude of health status benefit with vutrisiran versus placebo was estimated to correspond to a difference in age-related decline in the KCCQ-OSS of 11 years.

The authors do remark that the “KCCQ was designed as a composite measure of overall health status, and individual items have not been validated independently. [...] Thus, while prespecified, our results should be considered exploratory.”

Find this article online at Eur J Heart Fail.

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