Vericiguat misses endpoint in HFrEF trial

In the treatment of patients with heart failure and reduced ejection fraction (HFrEF) and no recent worsening, the use of vericiguat falls short of reducing the risk of the composite of cardiovascular death and HF hospitalization, as shown in a phase III study.

The study included 6,105 adult patients (median age 68 years, 23.6 percent female, 64.4 percent White) with HFrEF (left ventricular ejection fraction of ≤40 percent) without HF hospitalization within 6 months or outpatient intravenous diuretic use within 3 months. These patients were randomly assigned to receive oral vericiguat at a target dose of 10 mg (n=3,053) or matching placebo (n=3,052).

The primary endpoint of a composite of time to cardiovascular death or HF hospitalization was assessed in the intent-to-treat population. Adverse events were evaluated in all randomly assigned patients who received at least one dose of study drug (safety population).

Over a median follow-up of 18.5 months, primary outcome events occurred in 18 percent of patients in the vericiguat group vs 19.1 percent in the placebo group (hazard ratio [HR], 0.93, 95 percent confidence interval [CI], 0.83–1.04; p=0.22). Since the primary endpoint was not met, all analyses of secondary and exploratory endpoints had been considered nominal, as prespecified in the protocol.

Cardiovascular death occurred in 9.6 percent of patients on vericiguat vs 11.3 percent of those on placebo (HR, 0.83, 95 percent CI, 0.71–0.97). HF hospitalization was documented in 11.4 percent vs 11.9 percent, respectively (HR, 0.95, 95 percent CI, 0.82–1.10).

Serious adverse events (AEs) occurred in 23.5 percent of patients on vericiguat vs 24.6 percent of those on placebo, with symptomatic hypotension being the most common (11.3 percent vs 9.2 percent). All-cause death was reported in 12.3 percent vs 14.4 percent of patients, respectively (HR, 0.84, 95 percent CI, 0.74–0.97).