Vericiguat for heart failure reduces hospitalization, but not mortality

Reference

Armstrong PW, Pieske B, Anstrom KJ, et al, for the VICTORIA Study Group. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med 2020;382(20):1883-1893.

Synopsis

Vericiguat is a guanylate cyclase stimulator; another drug in this category, riociguat, is approved for treatment of idiopathic pulmonary arterial hypertension. For this trial, the researchers enrolled 5050 adults with New York Heart Association class II - IV heart failure with an ejection fraction of less than 45%, and an elevated natriuretic peptide level. The patients also had to have evidence of worsening heart failure based on recent hospitalization or need for intravenous diuresis. Patients were randomized to receive a starting dose of vericiguat 2.5 mg once daily or matching placebo, with an increase to 5 mg and eventually 10 mg, if tolerated (which approximately 90% did). There were a range of individual and composite outcomes, adjudicated by a committee masked to treatment assignment. Groups were balanced at baseline and analysis was by intention to treat. The patients' average age was 67 years, 76% were men, and approximately two-thirds had been hospitalized in the previous 3 months. The primary outcome was a composite of cardiovascular death and hospitalization for heart failure—two outcomes it makes absolutely no sense to combine (one is really bad, one is transiently sort of bad). The median follow-up was only 10.8 months. There was a statistically significant reduction for the primary outcome (35.5% vs 38.5%; P = .02; NNT = 33). This was largely due to fewer hospitalizations (27.4% vs 29.6%; P = .05; NNT = 45). There was no significant difference in the risk of cardiovascular mortality (16.4% vs 17.5%; hazard ratio [HR] 0.93; 0.81 - 1.06) or all-cause mortality (20.3% vs 21.2%; HR 0.95; 0.84 - 1.07). In a subgroup analysis, mortality was higher in the treatment group when NT-proBNP was greater than 5314 pg/mL. All other subgroup analyses showed no significant differences. Anemia was more common in the treatment group (7.6% vs 5.7%). The cost of vericiguat has not yet been determined.