Key result
Vutrisiran reduces all-cause mortality ~36% vs. placebo in patients with ATTR-CM.
Why the study?
Does vutrisiran reduce mortality and cardiovascular events in patients with transthyretin amyloidosis with cardiomyopathy?
RCT (n=655)
Double-blind
Does vutrisiran reduce mortality and cardiovascular events in patients with transthyretin amyloidosis with cardiomyopathy?
Hazard Ratio: 0.64 (95% CI 0.46–0.88)
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Early diagnosis and treatment of amyloidosis is mandatory, and vutrisiran may become a standard for newly diagnosed patients and those progressing on stabilizing therapies.”
“These results demonstrate the robust and consistent effect of vutrisiran across a spectrum of CV and heart failure outcomes, with a large impact on urgent heart failure visits. These data reinforce the positive results from the HELIOS-B primary analysis and further demonstrate the beneficial effect of vutrisiran on mortality rates and CV health for patients with ATTR cardiomyopathy.”
“These new data—including the impact on mortality, on cardiovascular events and on urgent heart failure visits, the latter of which was reduced by nearly half—add to the story of consistency and magnitude of benefit. I remain impressed by the HELIOS-B results, which are noteworthy given the substantial use of heart failure treatments in the study population, and I believe they continue to reinforce Amvuttra as a clinically differentiated, first-line option for patients with ATTR-CM.”
Vutrisiran significantly improves survival and reduces cardiovascular and heart failure hospitalizations in patients with ATTR-CM.
BACKGROUND: Patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) have high mortality and morbidity. Vutrisiran, a subcutaneous RNA interference therapeutic, reduced the composite of all-cause mortality (ACM) and cardiovascular (CV) events (CV hospitalizations and urgent heart failure [HF] visits) in HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy) in patients with ATTR-CM. OBJECTIVES: Here we present data from HELIOS-B evaluating the impact of vutrisiran on ACM and CV mortality with additional patient follow-up through 42 months, and CV events such as CV hospitalizations, HF hospitalizations, and urgent HF visits. METHODS: The HELIOS-B trial randomized 655 patients to vutrisiran 25 mg or placebo once every 3 months for up to 33 to 36 months in the double-blind (DB) period, followed by an open-label extension. Prespecified mortality and CV mortality analyses used data through 39 to 42 months of follow-up (DB period and up to 6 months of the open-label extension). CV hospitalizations and HF events were evaluated over the DB period of 33 to 36 months. Differences between vutrisiran and placebo were evaluated in the overall population, and in those stratified by baseline tafamidis use. RESULTS: In the overall population, vutrisiran reduced the risk of ACM (HR: 0.64; 95% CI: 0.46-0.88) and CV mortality (HR: 0.67; 95% CI: 0.47-0.96) vs placebo. Vutrisiran also reduced the risk of a composite of CV mortality and CV events (HR: 0.72; 95% CI: 0.55-0.94), and lowered rates of CV hospitalizations (rate ratio [RR]: 0.75; 95% CI: 0.62-0.91), urgent HF visits (RR: 0.54; 95% CI: 0.30-0.98), and HF hospitalizations (RR: 0.67; 95% CI: 0.52-0.86) vs placebo. Consistent trends were seen regardless of baseline tafamidis use. CONCLUSIONS: Consistent with the primary trial results, vutrisiran reliably reduced the risk of ACM, CV mortality, CV hospitalizations, HF hospitalizations, and urgent HF visits vs placebo in patients with ATTR-CM. (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149).
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Witteles et al. (2025) conducted an RCT in Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) (n=655). Vutrisiran vs. Placebo was evaluated on All-cause mortality (ACM) (HR 0.64, 95% CI 0.46-0.88). Vutrisiran reduced the risk of all-cause mortality (HR 0.64; 95% CI 0.46-0.88) and cardiovascular mortality (HR 0.67; 95% CI 0.47-0.96) compared to placebo in patients with ATTR-CM.
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