Effect of vutrisiran on components of health status in transthyretin amyloidosis with cardiomyopathy: the HELIOS-B study

Abstract Aims Vutrisiran was shown to maintain overall health status, as measured by the 23-item Kansas City Cardiomyopathy Questionnaire-overall summary score (KCCQ-OSS), in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) in HELIOS-B. We assessed individual KCCQ components to better contextualize changes in KCCQ-OSS in a manner relevant to patients and clinicians. Methods In this analysis of HELIOS-B, a double-blind, randomized, placebo-controlled trial of vutrisiran in ATTR-CM, we assessed treatment effect on mean score changes from baseline to 30 months for each 23 KCCQ components (scaled from 0 [worst] to 100 [best]) using a multivariable linear regression model. We further assessed overall changes in KCCQ-OSS as a function of age in both treatment groups to estimate the age-equivalent benefit observed. Results Of 654 participants in HELIOS-B, 486 completed KCCQ assessment both at baseline and 30 months (age: 75 ± 6 years; 93% male; 91% wild-type ATTR; baseline KCCQ-OSS: 74.6 ± 18.9). Vutrisiran, compared with placebo, was associated with more favourable changes in most KCCQ components (median: +3.8, range: −0.9 to +7.6). The greater differences favouring vutrisiran were observed in ‘hurrying or jogging’, ‘walking on level ground,’ and ‘discouraged/down with heart failure’. Similar or greater benefits with vutrisiran were observed in patients not on tafamidis at baseline. KCCQ-OSS at 30 months was inversely related to age, with vutrisiran shifting the age-KCCQ-OSS relationship by approximately 11 years (95%CI: 3–20 years). Conclusions In HELIOS-B, vutrisiran was associated with improvement in a wide range of individual KCCQ components, with the greatest benefits observed in physical limitations and quality-of-life domains.