Additional follow-up shows vutrisiran reduces mortality and CV event risks in ATTR-CM
ESC Heart Failure 2025 – In additional analyses of HELIOS-B, vutrisiran lowered the risks of all-cause and CV mortality at 42 months and rates of CV events at 36 months compared with placebo in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).
This summary is based on the presentation of Marianna Fontana, MD, PhD (London, UK) at the ESC Heart Failure Congress 2025 - Vutrisiran Reduces All-Cause Mortality, Cardiovascular Mortality and Cardiovascular Events in Patients with Transthyretin Amyloid Cardiomyopathy: Analysis from the HELIOS-B Trial.
Introduction and methods
Transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal disease characterized by the deposition of amyloid fibrils, which consist of misfolded transthyretin (TTR) aggregates, in the myocardium. The HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy) trial showed that vutrisiran, an siRNA that inhibits the production of amyloidogenic TTR protein, reduced the risk of the composite outcome of all-cause mortality or CV events compared with placebo in ATTR-CM patients during the double-blind period (33–36 months). The all-cause mortality risk was reduced at 42 months (including 6-month open-label extension (OLE) phase). At the time of the data cut for the primary analysis (May 8, 2024), vital status was ascertained in >99% of the randomized patients, and data up to 42 months were available for 42.4% of the still participating patients.
In a prespecified analysis of the HELIOS-B trial, the effects of vutrisiran on all-cause and CV mortality up to 42 months (data cut: November 22, 2024) were assessed, whereas the effects on CV and HF events up to 36 months were examined in a post-hoc analysis. The HELIOS-B trial was a global, multicenter, placebo-controlled, double-blind, phase 3 RCT in which 654 ATTR-CM patients were randomized to subcutaneous vutrisiran 25 mg or placebo every 3 months for up to 36 months, after which eligible participants could enter the OLE phase to receive vutrisiran 25 mg every 3 months up to 2 years. Treatment with tafamidis (either at baseline or initiated during the trial) was permitted.
The endpoints of the current analysis included all-cause mortality, CV death, recurrent CV events (i.e., CV hospitalizations and urgent HF visits), and HF hospitalizations.
Main results
- At 42 months, treatment with vutrisiran reduced the risks of all-cause mortality (HR: 0.64; 95%CI: 0.46–0.88; P=0.007) and CV death (HR: 0.67; 95%CI: 0.47–0.96; P=0.038) compared with placebo.
- Vutrisiran also lowered the incidence rates of recurrent CV events (rate ratio (RR): 0.73; 95%CI: 0.61–0.88; P<0.001), CV hospitalizations (RR: 0.75; 95%CI: 0.62–0.91; P=0.004), urgent HF visits (RR: 0.54; 95%CI: 0.30–0.98; P=0.041), and HF hospitalizations (RR: 0.67; 95%CI: 0.52–0.86; P=0.002) at 36 months, compared with placebo.
- Subgroup analysis for the CV event rate demonstrated generally consistent results across prespecified subgroups stratified by age, ATTR disease type, NYHA class, or baseline NT-proBNP level.
- Similar trends were seen in patients with no tafamidis use at baseline.
Conclusion
In these prespecified and post-hoc analyses of the HELIOS-B trial, vutrisiran reduced the risks of all-cause and CV mortality at 42 months and rates of CV events (including CV hospitalizations, HF hospitalizations, and urgent HF visits) at 36 months compared with placebo in ATTR-CM patients. Dr. Fontana concluded that “these data reinforce the positive results of the HELIOS-B primary analysis and further demonstrate the beneficial effects of vutrisiran on mortality risk and CV health in patients with ATTR-CM.”
- Our reporting is based on the information provided at the ESC Heart Failure Congress 2025 and publication of the data in J Am Coll Cardiol.-