Continuous Vutrisiran Reduces Cardiovascular Events and Hospitalizations in Patients With Transthyretin Amyloidosis With Cardiomyopathy in the HELIOS-B One-Year Open Label Extension

BACKGROUND: Vutrisiran significantly reduced the risk of all-cause mortality and recurrent cardiovascular (CV) events vs placebo in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) in the phase 3 HELIOS-B study (NCT04153149). Here, we report the long-term impact of vutrisiran on hospitalizations and urgent heart failure (HF) visits from the ongoing HELIOS-B open-label extension (OLE). METHODS: In HELIOS-B, patients received vutrisiran 25 mg or placebo every 3 months over a 33-36-month double-blind period, followed by a 24-month OLE continuing with vutrisiran (continuous treatment), or if previously receiving placebo, initiating vutrisiran (delayed treatment). Hospitalizations and urgent HF visits were analyzed through 48 months (12 months of the OLE) in the overall and monotherapy (not receiving tafamidis at baseline) populations, and the baseline tafamidis subgroup. RESULTS: Of 654 participants, 466 entered the OLE. Continuous vutrisiran reduced the risk of all-cause hospitalizations vs delayed treatment in the overall population (relative rate ratio [RRR] 0.71, 95% confidence interval [CI] 0.62-0.82, P<0.001) and the monotherapy population (RRR 0.60, 95% CI 0.50-0.72, P<0.001). Continuous vutrisiran also significantly reduced the risk of CV hospitalizations, HF hospitalizations, and non-CV hospitalizations vs delayed vutrisiran in the overall and monotherapy populations, and urgent HF visits in the overall population and baseline tafamidis subgroup. CONCLUSIONS: Continuous vutrisiran reduced the risk of CV events and hospitalizations relative to patients originally randomized to placebo in HELIOS-B. Many treatment effects were of greater magnitude at 48 months vs 36 months with continuous vutrisiran, highlighting the benefits of earlier diagnosis and treatment.