This trial sought to evaluate whether vericiguat, a novel oral soluble guanylate 
cyclase (sGC) stimulator, was superior to placebo, on a background of standard 
of care, in increasing the time to the first occurrence of the composite 
endpoints of cardiovascular (CV) death and heart failure (HF) hospitalization in 
patients with HF with reduced ejection fraction (HFrEF). Deficiency in 
sGC-derived cyclic guanosine monophosphate (cGMP) causes both myocardial 
dysfunction and impaired endothelium-dependent vasomotor regulation that 
includes the myocardial microcirculation. Experimental studies have suggested 
multiple potential benefits of sGC stimulators including prevention, or even 
reversal, of left ventricular hypertrophy and fibrosis, as well as reduction of 
ventricular afterload through both systemic and pulmonary vasodilation. Hence, 
restoration of sufficient nitric oxide (NO)-sGC-cGMP signaling has been proposed 
as an important treatment target in HF. Vericiguat has been shown to directly 
stimulate sGC and enhance sGC sensitivity to endogenous NO. Available phase IIb 
data in HFrEF patients indicate vericiguat is safe and well-tolerated, and 
exploratory analyses indicate that it results in a dose-dependent, clinically 
significant reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) 
at the highest tested dose. VICTORIA (Vericiguat Global Study in Subjects With 
Heart Failure With Reduced Ejection Fraction) is a randomized, 
placebo-controlled, parallel group, multicenter, double-blind, event-driven 
phase 3 trial of vericiguat in subjects with HFrEF. Approximately 4,872 subjects 
will be randomized to evaluate the efficacy and safety of vericiguat 
compared with placebo on a background of standard of care. After a screening 
phase of up to 30 days, eligible subjects will be treated until the required 
number of cardiovascular deaths is observed. The estimated median follow-up 
duration is approximately 18 months. All subjects will be followed until study 
completion to assess for the occurrence of endpoint events. VICTORIA will 
establish the efficacy and safety of vericiguat on cardiovascular death and HF 
hospitalization in patients with HFrEF. (A Randomized Parallel-Group, 
Placebo-Controlled, Double-Blind, Event-Driven, Multi-Center Pivotal Phase III 
Clinical Outcome Trial of Efficacy and Safety of the Oral sGC Stimulator 
Vericiguat in Subjects With Heart Failure With Reduced Ejection Fraction 
[HFrEF]-VerICiguaT Global Study in Subjects With Heart Failure With Reduced 
Ejection Fraction [VICTORIA]; NCT02861534).