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TOPLINE:

Lowering levels of circulating transthyretin with vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) decreased their risk for mortality and cardiovascular events compared with placebo and was associated with maintained or improved functional ability, health status, and quality of life.

METHODOLOGY:

• In the previously conducted HELIOS-B study, patients with ATTR-CM who received vutrisiran had a reduced risk for all-cause mortality and cardiovascular events, along with improvements in functional capacity and quality of life and a favorable safety profile, compared with placebo.
• Researchers conducted a predefined secondary analysis of the HELIOS-B study at 30 months to assess the effect of vutrisiran vs placebo in improving or maintaining functional capacity, health status, and quality of life.
• The analysis included adults with wild-type or hereditary ATTR-CM and a history of heart failure who had previously received vutrisiran (n = 263) or placebo (n = 247) and completed the 30-month visit. A subgroup of patients receiving vutrisiran monotherapy without tafamidis at baseline was also included.
• Functional capacity was assessed using the 6-minute walk test distance, with worsening defined as a decrease of more than 7 m, 15 m, or 35 m from baseline.
• Health status and quality of life were evaluated using the Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS), with worsening defined as a decrease of more than 5 or 10 points from baseline.

TAKEAWAY:

• At 30 months, a significantly higher proportion of patients treated with vutrisiran showed a maintained or improved distance on the 6-minute walk test across all cutoffs than those treated with placebo (49.6% vs 33.2% for > 7 m; 55.5% vs 38.6% for > 15 m; and 68.5% vs 51.6% for > 35 m; P < .001 for all).
• KCCQ-OS scores stayed the same or improved in a significantly higher proportion of patients treated with vutrisiran than those treated with placebo (63.5% vs 46.6% for > 5 points; P < .001; 74.6% vs 60.7% for more than 10 points; P < .01).
• The findings were consistent in the group who received vutrisiran without tafamidis at baseline.
• The benefits of vutrisiran were consistent across all prespecified subgroups and questionnaire subdomains, including physical function, total symptoms, quality of life, and social limitation.

IN PRACTICE:

“These results further support the beneficial impact of vutrisiran on the daily functioning and [quality of life] in a broad spectrum of patients with ATTR-CM,” the authors of the study wrote.

SOURCE:

This study was led by Farooq H. Sheikh, MD, of the Georgetown University School of Medicine in Washington, DC. It was published online on April 9, 2025, in JACC.

LIMITATIONS:

The analyses of maintenance or improvement were conducted post hoc, and additional subgroup analyses were not powered for statistical significance. Although various cutoff values for the observed outcomes were used based on prior research, none were specifically validated for the ATTR-CM population. The interpretation of the findings may be limited by the predominance of patients with wild-type ATTR-CM.

DISCLOSURES:

This study was funded by Alnylam Pharmaceuticals Inc, which makes vutrisiran. Two authors declared being employees and stockholders of Alnylam Pharmaceuticals Inc. Several other authors reported receiving consulting fees, research grants, honoraria, speaker fees, and other ties with various pharmaceutical and bioscience companies including the funding agency.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.