Patients with worsening chronic HFrEF despite standard therapy may benefit from a novel soluble guanylate cyclase stimulator, vericiguat, a randomised controlled trial shows.
The addition of vericiguat to usual care for patients with reduced ejection fraction heart failure (HFrEF) significanly lowered their incidence of death from cardiovascular causes or hospitalisation for heart failure.
The phase 3 VICTORIA RCT of more than 5,000 patients from hundreds of sites across 42 countries including Australia compared 2.5 -10 mg vericiguat, a novel oral soluble guanylate cyclase stimulator, to placebo.
After a median follow-up of 10.8 months, a composite of CVD death or hospitalisation for heart failure was observed in 35.5% of vericiguat treated patients versus 38.5% in controls (p<0.002).
CVD deaths occurred in 16.4% of the vericiguat group versus 17.5% of controls while hospitalisation for heart failure occurred in 27.4% of the vericiguat group compared to 29.6% of controls.
A secondary composite of all cause deaths and hospitalisation for heart failure was also lower in the vericiguat groups than controls (37.9% v 40.9%).
The study, published in the NEJM, found serious adverse events occurred in about a third of both patient groups (32.8% v 34.8%).
Prespecified adverse events of clinical interest – symptomatic hypotension (9.1% v 7.9%) and syncope (4.0% v 3.5%) – were numerically but not statistically more common in vericiguat treated patients than controls.
The investigators calculated the number needed to treat with vericiguat for 1 year to prevent a primary-outcome event was about 24 patients
“In this trial involving patients with chronic heart failure and a reduced ejection fraction who had worsening symptoms for which hospitalization or urgent treatment was warranted, the incidence of the composite of death from cardiovascular causes or hospitalization for heart failure was lower with vericiguat than with placebo,” they said.
They said new treatment options were particularly important as the prevalence of heart failure is expected to increase.
“This is especially true in the emerging era of precision medicine, since patients and providers are searching for personalized treatment based on anticipated benefits, a favorable side-effect profile, value, and ease of use.”
An accompanying editorial said the promising trial results “constitute another victory for cyclic GMP–based therapy for heart failure”.
“A key design aspect of VICTORIA was the recruitment of sicker patients with higher NT-proBNP levels than those in previous heart-failure trials; this selection resulted in high event rates.”
“Furthermore, the patients were older than those in previous large-scale heart-failure trials; this factor is clinically relevant, since heart failure is often a disease of the elderly.”
The author noted that the results of an ongoing study of vericiguat in patients with HFpEF were anxiously awaited.