Vericiguat and mortality in heart failure and reduced ejection fraction: the VICTOR trial

In the VICTOR trial (NCT05093933), vericiguat was neutral for the primary composite endpoint of cardiovascular death or hospitalization for heart failure (HF). VICTOR was powered to independently assess cardiovascular death. This study reports detailed analysis on the effects of vericiguat on mortality. VICTOR, a double-blind, placebo-controlled, randomized trial, enrolled 6105 ambulatory patients with HF and reduced ejection fraction (HFrEF) without recent worsening and randomized them to vericiguat or placebo. The main outcome for this analysis was the prespecified secondary endpoint of cardiovascular death. All-cause death, sudden cardiac death, and death related to HF were also assessed. Over a median of 19.7 months (interquartile range 14.6-25.4), cardiovascular deaths occurred in 292 patients (5.7 deaths per 100 patient-years) and 346 patients (6.8 deaths per 100 patient-years) in the vericiguat and placebo groups, respectively (hazard ratio HR 0.83, 95% confidence interval CI 0.71-0.97; P = 0.020). Risk of death from any cause was lower with vericiguat vs placebo (377 7.3 deaths per 100 patient-years vs 440 8.6 deaths per 100 patient-years; HR 0.84, 95% CI 0.74-0.97; P = 0.015). Sudden cardiac death and HF-related deaths were lower with vericiguat vs placebo (1.6 vs 2.2 events per 100 patient-years; HR 0.75, 95% CI 0.56-0.99; P = 0.042 and 1.7 vs 2.4 events per 100 patient-years; HR 0.71, 95% CI 0.54-0.94; P = 0.016, respectively). Lower mortality rates were consistent across subgroups including baseline therapy. Consistent cardiovascular and all-cause mortality benefit was seen across baseline N-terminal pro-B-type natriuretic peptide levels. In ambulatory well-treated participants with HFrEF, vericiguat was associated with clinically meaningful reductions in the key secondary outcome of cardiovascular death, as well as all-cause mortality.