Vericiguat reduces CV death, HF hospitalization in high-risk HF patients

Vericiguat significantly reduces cardiovascular (CV) deaths and heart failure (HF)-related hospitalizations in patients with high-risk HF, according to results of the VICTORIA trial presented at the American College of Cardiology and World Congress of Cardiology virtual meeting (ACC.20/WCC).

“Vericiguat achieved a clinically meaningful absolute primary event reduction of 4.2 per 100 patient-years in the presence of guideline-based care. The number needed to treat with vericiguat for 1 year to prevent one primary outcome event of CV death or first HF hospitalization was approximately 24 in this high-risk population of patients with HF with reduced ejection fraction [HFrEF],” said investigator Professor Paul Armstrong from the Duke University School of Medicine in Durham, Canada. [Armstrong P, et al, ACC.20/WCC, abstract 402-08; N Engl J Med 2020, doi: 10.1056/NEJMoa1915928]

Vericiguat is a novel soluble guanylate cyclase (sGC) stimulator that directly enhances the cyclic guanosine monophosphate (GMP) pathway.

The VICTORIA study population consisted of 5,050 patients (mean age, 67 years; male, 76 percent) with chronic HF (defined as New York Heart Association [NYHA] class II, III or IV), a rEF (<45 percent) and an elevated natriuretic peptide (NP) level. Enrolled patients also had evidence of a worsening HF event (indicated by recent HF hospitalization or intravenous diuretic use). Patients were randomized (1:1) to receive vericiguat (started at 2.5 mg daily, increased to 5 mg daily, then 10 mg daily) vs placebo for 12 months. At baseline, the patients’ mean EF was 29 percent and median N-terminal pro–B-type NP (NT-proBNP) was 2,816 pg/mL.

At a median follow-up of 10.8 months, the incidence of the primary outcome event (composite of death from CV causes or first hospitalization for HF) was significantly reduced with vericiguat vs placebo (35.5 percent vs 38.5 percent; hazard ratio [HR], 0.90; 95 percent confidence interval [CI], 0.82 to 0.98; p=0.019). This translated into an absolute event reduction of 4.2 per 100 patient-years.

Consistent benefit in terms of the primary composite outcome was demonstrated with vericiguat across most prespecified subgroups, except those ≥75 years (HR, 1.04; 95 percent 0.88 to 1.21) and those with high NT-proBNP level (>5314.0 pg/ml, HR, 1.16; 95 percent CI, 0.99 to 1.35).

When components of the primary composite outcome were analyzed individually, vericiguat was associated with a significant reduction in first HF hospitalization (27.4 percent vs 29.6 percent; HR, 0.90; 95 percent CI, 0.81 to 1.00; p=0.048) and only a numerical reduction in CV death (16.4 percent vs 17.5 percent; HR, 0.93; 95 percent CI, 0.81 to 1.06, p=0.269).

A significant reduction in the incidence of the composite secondary outcome (all-cause mortality and first HF hospitalization) was observed with vericiguat vs placebo (37.9 percent v 40.9 percent; HR, 0.90; 95 percent CI, 0.83 to 0.98; p=0.021).

A target dose of 10 mg of vericiguat was well tolerated in 89.2 percent of patients at 12 months, without adverse effects (AEs) on renal function or electrolytes.

Symptomatic hypotension and syncope appeared to be more common with vericiguat vs placebo (symptomatic hypotension, 9.1 percent vs 7.9 percent; p=0.121) (syncope, 4.0 percent vs 3.5 percent; p=0.303). Serious AEs occurred in 32.8 percent vs 34.8 percent of patients in the vericiguat vs placebo arms.

“Vericiguat is a once-daily medicine that is easy to use, generally safe and well tolerated, without the need for monitoring of renal function or electrolytes. It may play a useful role in patients with a recent worsening HF event,” concluded Armstrong.