Among patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM), vutrisiran reduced the risk of outpatient worsening heart failure (HF) – which was itself associated with a 2.6-fold increased risk of all-cause mortality and cardiovascular events. Furthermore, vutrisiran treatment reduced the risk of outpatient worsening HF, all-cause mortality and recurrent cardiovascular events compared with placebo, according to a prespecified analysis of the HELIOS-B study, presented at AHA 2024 and simultaneously published in JACC.

In the double-blind, multicenter study, Marianna Fontana, MD, and colleagues randomized patients with ATTR-CM 1:1 to receive vutrisiran 25 mg (326 patients) or placebo (328 patients) subcutaneously every three months for up to 36 months.

Results showed that patients with outpatient worsening HF – defined as an initiation of or a sustained increase for seven days or more of a daily dose of oral loop diuretics – had greater risk of the primary endpoint composite of death from any cause and recurrent cardiovascular events (hazard ratio [HR] 2.58; 95% confidence interval [CI]: 2.04-3.27), as well as an increased risk in all-cause mortality (HR: 2.45; 95% CI: 1.70-3.52). Outpatient worsening HF was also associated with a lowered functional capacity and quality of life, as well as increases in NT-proBNP.

Treatment with vutrisiran reduced the risk of first outpatient worsening HF by 27% (HR: 0.73; 95% CI: 0.59-0.91) and of recurrent outpatient worsening HF by 34% (relative rate ratio: 0.66; 95% CI: 0.56-0.78). It also reduced the risk of recurrent outpatient worsening HF, current cardiovascular events and death (HR: 0.69; 95% CI: 0.57-0.83).

"With growing disease awareness, patients are being diagnosed at earlier stages of ATTR-CM, thus raising the need to identify those at risk before occurrence of [cardiovascular] events. Outpatient worsening HF as a prognostic marker also has the advantage of being simple to assess in clinical practice," Fontana and colleagues write, adding that, "The results provide further evidence of the therapeutic benefit of vutrisiran."