Vericiguat in patients with heart failure and reduced ejection fraction.

ABSTRACT

BACKGROUND: The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear. METHODS: In this phase 3, randomized, double-blind, placebo-controlled trial, we assigned 5 050 patients with chronic heart failure (New York Heart Association class II, III, or IV) and an ejection fraction of less than 45% to receive vericiguat (target dose 10 mg once daily) or placebo, in addition to guideline-based medical therapy.The primary outcome was a composite of death from cardiovascular causes or first hospitalization for heart failure. RESULTS: Over a median of 10.8 months, a primary-outcome event occurred in 897 of 2 526 patients (35.5%) in the vericiguat group and in 972 of 2 524 patients (38.5%) in the placebo group (p = 0.02). A total of 691 patients (27.4%) in the vericiguat group and 747 patients (29.6%) in the placebo group were hospitalized for heart failure. Death from cardiovascular causes occurred in 414 patients (16.4%) in the vericiguat group and in 441 patients (17.5%) in the placebo group. The composite endpoint of death from any cause or hospitalization for heart failure occurred in 957 patients (37.9%) in the vericiguat group and in 1 032 patients (40.9%) in the placebo group (p = 0.02). Symptomatic hypotension occurred in 9.1% of the patients in the vericiguat group and in 7.9% of the patients in the placebo group (p = 0.12), syncope occurred in 4.0% of the patients in the vericiguat group and in 3.5% of the patients in the placebo group (p = 0.30). CONCLUSION: Among patients with high-risk heart failure, the incidence of death from cardiovascular causes or hospitalization for heart failure was lower among those who received vericiguat than those who received placebo.