HELIOS-B
Trial question
What is the role of vutrisiran, an siRNA silencing the mRNA encoding transthyretin, in patients with transthyretin amyloidosis with cardiomyopathy?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
7.0% female
93.0% male
N = 654
654 patients (49 female, 605 male).
Inclusion criteria: adult patients with transthyretin amyloidosis with cardiomyopathy.
Key exclusion criteria: NYHA class IV or a NYHA class III with a National Amyloidosis Center transthyretin amyloidosis stage 3; polyneuropathy disability score of IIIa, IIIb, or IV; cardiomyopathy not associated with transthyretin amyloidosis; eGFR < 30 mL/min/1.73 m².
Interventions
N=326 vutrisiran (at a dose of 25 mg every 12 weeks for up to 36 months).
N=328 placebo (matching placebo every 12 weeks for up to 36 months).
Primary outcome
Death from any cause and recurrent CV events
50%
62%
62.0 %
46.5 %
31.0 %
15.5 %
0.0 %
Vutrisiran
Placebo
Significant
decrease ▼
NNT = 8
Significant decrease in death from any cause and recurrent CV events (50% vs. 62%; HR 0.72, 95% CI 0.56 to 0.93).
Secondary outcomes
Significant decrease in the rate of death from any cause through 42 months (18% vs. 26%; HR 0.65, 95% CI 0.46 to 0.9).
Significantly lower reduction in least-squares mean decline in the distance covered on the 6-minute walk test at 30 months (45.4 m vs. 71.9 m; MD -26.5, 95% CI -39.6 to -13.4).
Significantly lower reduction in least-squares mean decline in Kansas City Cardiomyopathy Questionnaire-Overall Summary score at 30 months (9.7 points vs. 15.5 points; MD -5.8, 95% CI -9.2 to -2.4).
Safety outcomes
No significant difference in adverse events.
Conclusion
In adult patients with transthyretin amyloidosis with cardiomyopathy, vutrisiran was superior to placebo with respect to death from any cause and recurrent CV events.
Reference
Marianna Fontana, John L Berk, Julian D Gillmore et al. Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. N Engl J Med. 2025 Jan 2;392(1):33-44.
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