Effects of Vutrisiran on Cardiac Function and Outcomes in Patients With Transthyretin Amyloidosis With Cardiomyopathy
Key result
Vutrisiran attenuates LVEF decline by ~1.6% vs placebo at 18 months in ATTR-CM.
- MD 1.6%
- 95% CI 0.1-3.2
- n=655
Why the study?
To investigate associations between echocardiographic measures of cardiac structure and function and clinical outcomes, and assess if favorable changes with vutrisiran were associated with improved outcomes in ATTR-CM.
Does vutrisiran improve echocardiographic measures of cardiac function and reduce the composite of all-cause death and recurrent cardiovascular events in patients with ATTR-CM?
Key Points
- This research aims to evaluate the impact of vutrisiran on cardiac function and associated clinical outcomes in transthyretin amyloidosis patients.
- Randomized 655 patients with ATTR-CM to vutrisiran or placebo.
- Conducted echocardiograms at baseline, 12, 18, 24, and 30 months.
- Analyzed associations using modified Andersen-Gill models, adjusting for key variables.
- Vutrisiran improved left ventricular ejection fraction by 1.6% (95% CI: 0.1-3.2) at 18 months.
- Major echocardiographic parameters were significantly correlated with the primary composite outcome.
- Attenuated declines in global longitudinal strain and tricuspid annular systolic myocardial velocity at 18 months.
Study Design
Type
RCT (n=655)
Randomization
randomized
Structured PICO
Does vutrisiran improve echocardiographic measures of cardiac function and reduce the composite of all-cause death and recurrent cardiovascular events in patients with ATTR-CM?
P
Population
655 patients with transthyretin amyloid cardiomyopathy (median age 77, 93% male) randomized to vutrisiran or placebo and followed for up to 30 months.
I
Intervention
Vutrisiran 25 mg subcutaneously every 12 weeks
C
Comparator
Placebo
O
Outcome
Composite outcome of all-cause death and recurrent cardiovascular eventscomposite
Main Result
Mean Difference: 1.6 (95% CI 0.1–3.2)
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Vutrisiran was highly effective and well tolerated in this contemporary population representative of patients that we see in our clinics, with consistent benefits regardless of background tafamidis therapy. Our findings indicate that vutrisiran has the potential to become the new standard of care. This trial is also important as it is the first to show the benefit of gene silencers in any type of cardiomyopathy.”
“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.”
“Increasing NT-ProBNP at six months helps identify patients at highest cardiovascular risk at a relatively early time point. Earlier identification may prompt additional heart failure therapy optimization and interventions or refinement of patient/clinician expectations on the patient's clinical course.”
Implication
Vutrisiran attenuates declines in biventricular systolic function over 18 months in patients with ATTR-CM, which is associated with a reduced risk of all-cause death and recurrent cardiovascular events.
Abstract
BACKGROUND Transthyretin amyloid cardiomyopathy (ATTR-CM), caused by deposition of transthyretin amyloid fibrils in the heart, is associated with high morbidity and mortality. In HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy), the RNA interference therapeutic agent vutrisiran reduced rates of the primary composite outcome of all-cause death and recurrent cardiovascular events among patients with ATTR-CM and had beneficial effects on cardiac structure and function over 30 months. OBJECTIVES The purpose of this study was to investigate associations of echocardiographic measures of cardiac structure and function with the primary outcome and to assess whether favorable changes in cardiac structure and function with vutrisiran were associated with improvements in outcomes. METHODS HELIOS-B randomized 655 patients with ATTR-CM to vutrisiran (25 mg subcutaneously every 12 weeks) or placebo. Echocardiograms were performed at baseline and months 12, 18, 24, and 30. Associations of baseline echocardiographic parameters with the primary outcome were analyzed using modified Andersen-Gill models adjusted for age, sex, ATTR disease type, and National Amyloidosis Centre stage, and stratified by baseline tafamidis use and treatment assignment. Changes in cardiac function from baseline to month 18 were compared between treatment arms and related to outcomes in landmark analyses. RESULTS Among the 654 participants with available echocardiographic data (median age 77 years, 93% male, 88% wild-type transthyretin), baseline left and right ventricular systolic and diastolic function were independently associated with the primary outcome (HR per unit increase, left ventricular ejection fraction, 0.90 per 5% increase, 95% CI: 0.86-0.95; absolute global longitudinal strain, 0.92 per 1% increase, 95% CI: 0.89-0.96; tricuspid annular systolic myocardial velocity, 0.94 per 1-cm/s increase, 95% CI: 0.90-0.98; average E/e', 1.03 per 1-U increase, 95% CI: 1.01-1.04). At 18 months, vutrisiran attenuated declines in left ventricular and right ventricular systolic function (least squares mean difference: left ventricular ejection fraction, 1.6%, 95% CI: 0.1-3.2; absolute global longitudinal strain, 0.7%, 95% CI: 0.3-1.2; tricuspid annular systolic myocardial velocity, 0.5 cm/s, 95% CI: 0.1-0.9). Worsening in these parameters at 18 months was associated with a heightened risk of the primary outcome. CONCLUSIONS Echocardiographic measures of biventricular systolic and diastolic function provide important prognostic information beyond National Amyloidosis Centre stage in patients with ATTR-CM. Vutrisiran improved diastolic function and attenuated declines in left ventricular and right ventricular systolic function over 18 months. The benefits on cardiac function with vutrisiran may partly underlie its beneficial effects on clinical outcomes.
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Cite This Study
Jering et al. (2025) conducted an RCT in Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) (n=655). Vutrisiran vs. Placebo was evaluated on Change in left ventricular ejection fraction at 18 months (MD 1.6%, 95% CI 0.1-3.2). In patients with ATTR-CM, vutrisiran attenuated declines in left ventricular ejection fraction at 18 months compared with placebo (mean difference 1.6%; 95% CI 0.1-3.2).