In patients with ATTR-CM, vutrisiran reduced the mean days lost to death and/or hospitalization by 32.2 days (95% CI 5.3-59.3) compared to placebo over a 3-year period.
RCT (n=654)
Does vutrisiran reduce days lost to death and/or hospitalization in patients with transthyretin amyloidosis with cardiomyopathy?
In patients with ATTR-CM, vutrisiran reduced the mean days lost to death and/or hospitalization by more than 1 month over a 3-year period compared to placebo.
Mean Difference: -32.2 (95% CI -59.3–-5.3)
Abstract Background In HELIOS-B, vutrisiran reduced the risk of the primary composite endpoint of all-cause mortality (ACM) and cardiovascular (CV) events (CV hospitalizations and urgent heart failure visits) vs placebo in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and also met all secondary endpoints. While the primary composite endpoint in HELIOS-B provides the central evidence for the efficacy of vutrisiran in reducing ACM and CV event risk, additional analyses that capture the distinctions between death and hospitalizations of differing lengths may provide additional insight into the efficacy of vutrisiran. Purpose This analysis aims to further characterize the benefit of vutrisiran in patients with ATTR-CM by assessing its effect on days lost to death and/or hospitalization (DLDH) in HELIOS-B. Methods The number of DLDH, and days lost to death and/or CV hospitalization (DLDCVH), were calculated for each patient. Additionally, the remaining days (i.e., days not lost to death or hospitalization) were weighted based on functional and quality of life (QoL) assessments (Kansas City Cardiomyopathy Questionnaire-Overall Summary Score KCCQ-OS, or KCCQ-Total Symptom Score KCCQ-TSS and New York Heart Association NYHA functional class); the result of this weighting was then used to calculate the number of days without full health due to impaired function or QoL. DLDH and DLDCVH (with and without the addition of days not in full health due to functional/QoL impairment) for vutrisiran vs placebo were analyzed using a beta or zero-inflated beta model. Results 654 patients were included in the analysis (326 vutrisiran, 328 placebo). Vutrisiran treatment resulted in a mean of 32.2 (95% confidence intervals CI 5.3, 59.3) fewer DLDH over 3 years vs placebo, with a comparable benefit observed for DLDCVH (mean 32.0 95% CI 4.6, 59.5 fewer days lost over 3 years) (Table). Patients treated with vutrisiran had 64% greater odds of no DLDH and of no DLDCVH vs placebo. When additionally accounting for impaired function/QoL on days alive and not hospitalized, vutrisiran treatment led to a mean of 62.8 (95% CI 25.6, 99.8) and 64.4 (95% CI 27.4, 101.5) fewer days lost (weighted DLDH and DLDCVH, respectively) vs placebo when weighted by KCCQ-OS, and a mean of 49.5 (95% CI 22.5, 76.6) and 52.6 (95% CI 26.1, 79.0) fewer days lost (weighted DLDH and DLDCVH, respectively) vs placebo when weighted by KCCQ-TSS and NYHA class collectively (Table). Conclusion In patients with ATTR-CM, vutrisiran reduced the mean days lost to death and/or hospitalization by more than 1 month vs placebo over a 3-year period. The vutrisiran effect was greater when the impact of impaired function and QoL was accounted for.
Yilmaz et al. (2025) conducted an RCT in Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) (n=654). Vutrisiran vs. Placebo was evaluated on Days lost to death and/or hospitalization (DLDH) (32.2 fewer days, 95% CI 5.3-59.3). In patients with ATTR-CM, vutrisiran reduced the mean days lost to death and/or hospitalization by 32.2 days (95% CI 5.3-59.3) compared to placebo over a 3-year period.