A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy - HELIOS-B

Nov 26, 2024
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
Alnylam Pharmaceuticals
Date Presented:
08/30/2024
Date Published:
11/18/2024
Date Updated:
11/26/2024
Original Posted Date:
08/30/2024
References

Contribution To Literature:

Highlighted text has been updated as of November 18, 2024.

The HELIOS-B trial showed that vutrisiran was effective at preventing deaths and adverse events among patients with ATTR-CM.

Description:

The goal of the trial was to evaluate vutrisiran compared with placebo among patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The mechanism of action of vutrisiran is to interfere with the RNA-mediated production of hepatic transthyretin.

Study Design

  • Randomized
  • Parallel
  • Double-blind
  • Placebo-controlled

Patients with ATTR-CM were randomized to vutrisiran 25 mg (n = 326) vs. placebo (n = 329) every 12 weeks for up to 36 months. Patients could remain on tafamidis if they were already on this medication at enrollment.

  • Total number of enrollees: 655
  • Duration of follow-up: 42 months
  • Mean patient age: 76 years
  • Percentage female: 7%

Inclusion criteria:

  • Age 18-85 years
  • Patients with ATTR-CM (either variant or wild-type ATTR amyloidosis)
  • Evidence of cardiac involvement as assessed with transthoracic echocardiography, with an end-diastolic interventricular septal wall thickness exceeding 12 mm
  • Clinical history of heart failure

Exclusion criteria:

  • New York Heart Association (NYHA) class IV, or NYHA class III with a National Amyloidosis Centre ATTR stage 3 (defined as NT-proBNP >3000 pg/mL and estimated glomerular filtration rate [eGFR] <45 mL/min/1.73 m2)
  • Polyneuropathy disability score of IIIa, IIIb, or IV
  • Cardiomyopathy not associated with ATTR amyloidosis
  • eGFR <30 m:/min/1.73 m2

Other salient features/characteristics:

  • Taking tafamidis at baseline: 40%

Principal Findings:

The primary outcome of all-cause death or recurrent cardiovascular events for vutrisiran vs. placebo: hazard ratio (HR) 0.72, p = 0.01.

Secondary outcomes:

  • Among those not on tafamadis at baseline, the primary outcome of all-cause death or recurrent cardiovascular events for vutrisiran vs. placebo: HR 0.67, p = 0.02
  • Vutrisiran resulted in less of a decline in distance covered on the 6-minute walk: difference 26.5 m, p < 0.001

Association between outpatient worsening of heart failure and cardiovascular events:

  • Patients with outpatient worsening of heart failure were associated with increased risk of all-cause mortality: HR 2.58 (95% CI 2.04-3.27)
  • Vutrisiran vs. placebo was associated with reduced risk of worsening of heart failure: HR 0.66 (95% CI 0.56-0.78)

 

Interpretation:

Among patients with ATTR-CM, vutrisiran was beneficial. Vutrisiran compared with placebo was associated with a reduction in all-cause mortality and recurrent cardiovascular events. Results were similar among those on tafamidis at baseline. Vutrisiran also resulted in less of a decline in distance covered on the 6-minute walk. Outpatient worsening of heart failure was associated with poor prognosis (increased all-cause mortality); however, this was reduced with vutrisiran versus placebo.

References:

Fontana M, Maurer MS, Gillmore JD, et al. Outpatient Worsening Heart Failure in Patients With Transthyretin Amyloidosis With Cardiomyopathy in the HELIOS-B Trial. J Am Coll Cardiol 2024;Nov 18:[Epub ahead of print].

Fontana M, Berk JL, Gillmore JD, et al., for the HELIOS-B Trial Investigators. Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy. N Engl J Med 2024;Aug 30:[Epub ahead of print].

Presented by Dr. Marianna Fontana at the European Society of Cardiology Congress, London, UK, August 30, 2024.

Clinical Topics: Heart Failure and Cardiomyopathies

Keywords: Amyloidosis, Cardiomyopathies, ESC24, ESC Congress


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