Vutrisiran in transthyretin amyloid cardiomyopathy: a structured review of the HELIOS-B trial and its secondary analyses

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive infiltrative cardiomyopathy caused by myocardial deposition of misfolded transthyretin, leading to heart failure, conduction abnormalities, and functional decline. Recent therapeutic advances have shifted management toward disease-modifying strategies that target transthyretin production and stability. Vutrisiran, a subcutaneously administered small interfering RNA therapy, suppresses hepatic transthyretin synthesis and has emerged as a potential treatment option for ATTR-CM. This structured narrative review was prospectively registered in PROSPERO (CRD420261307493) and aimed to evaluate the efficacy and safety of vutrisiran in patients with ATTR-CM. A systematic literature search was conducted on 12 February 2026 across PubMed, ScienceDirect, Google Scholar, PubMed Central, and ClinicalTrials.gov. Study selection and screening were performed independently by two reviewers in accordance with PRISMA guidelines, with disagreements resolved by consensus. The review included one primary randomized controlled trial and associated secondary and post hoc analyses. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Vutrisiran reduced all-cause mortality (HR 0.65–0.72), cardiovascular events (HR 0.67–0.72), and recurrent events (RR 0.68–0.73) over a median follow-up of ~ 33 months (up to ~ 36 months). It improved functional capacity (6MWD + 26.5–32.1 m; KCCQ-OS + 5.8–8.7) and NYHA class stability/improvement (66–68% vs. 56–61%). Cardiac remodeling improved with reductions in LV mass (− 10.6 g/m²), LV wall thickness (− 0.4 mm), and improvements in LVEF (+ 1.6–2%) and GLS (+ 0.7–1.2%). Biomarkers were reduced (NT-proBNP and troponin I ratio 0.68). Benefits were greater in earlier disease stages and included fewer HF events (HR 0.73) and reduced days lost to death/hospitalization (− 32 to − 64). Safety remained favorable with low discontinuation (3.5%) and no new organ toxicity signals. Vutrisiran represents a disease-modifying therapy for transthyretin amyloidosis with cardiomyopathy, demonstrating consistent biochemical and clinical benefits alongside a generally favorable safety profile. These findings support its emerging role within the therapeutic landscape and underscore the potential of transthyretin-silencing strategies to improve patient outcomes. Nevertheless, further long-term follow-up and additional trials and real-world studies are needed to better define the durability of benefit and its optimal positioning within evolving treatment algorithms.