Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction - VICTORIA

Contribution To Literature:

Highlighted text has been updated as of September 13, 2021.

The VICTORIA trial showed that vericiguat was superior to placebo at improving heart failure outcomes.


The goal of the trial was to evaluate vericiguat compared with placebo among patients with chronic heart failure (CHF) due to reduced ejection fraction (EF). Vericiguat increases soluble guanylate cyclase activity. By stimulating production of cyclic guanosine monophosphate, this may help to improve myocardial and vascular function.

Study Design

  • Randomized
  • Double-blind
  • Parallel

Patients with CHF were randomized to vericiguat (n = 2,526) versus placebo (n = 2,524). Vericiguat started at 2.5 mg daily, increased to 5 mg daily, then 10 mg daily.

  • Total number of enrollees: 5,050
  • Duration of follow-up: 12 months
  • Mean patient age: 68 years
  • Percentage female: 24%

Inclusion criteria:

  • CHF; New York Heart Association class II-IV, left ventricular EF <45%, and guideline-directed heart failure therapy
  • Recent heart failure hospitalization or intravenous diuretic use
  • Elevated natriuretic peptides; N-terminal pro–B-type natriuretic peptide (NT-proBNP) ≥1000 pg/ml (≥1600 pg/ml if atrial fibrillation) or BNP ≥300 pg/ml (≥500 pg/ml if atrial fibrillation)
  • Clinically stable (systolic blood pressure ≥100 mm Hg and no intravenous diuretics for 24 hours)

Exclusion criteria:

  • Use of long-acting nitrates, phosphodiesterase type 5 inhibitor, riociguat
  • Awaiting heart transplantation, continuous intravenous diuretics, or current/anticipated ventricular assist device
  • Chronic kidney disease (estimated glomerular filtration rate 15 ml/min/1.73 m2) or dialysis
  • Severe pulmonary disease requiring continuous oxygen
  • Severe hepatic insufficiency
  • Correctable cardiac comorbidities

Other salient features/characteristics:

  • Mean EF: 29%
  • Target dose of vericiguat achieved in 89%

Principal Findings:

The primary outcome, cardiovascular death or hospitalization for heart failure, occurred in 35.5% of the vericiguat group compared with 38.5% of the placebo group (hazard ratio [HR] 0.90, p = 0.019). The risk of the primary outcome for vericiguat vs. placebo: among those aged <75 years (HR 0.84) and those ≥75 years (HR 1.04) (p for interaction = 0.030).

Secondary outcomes:

  • Cardiovascular death: 16.4% of the vericiguat group compared with 17.5% of the placebo group (p = 0.27)
  • All-cause death: 20.3% of the vericiguat group compared with 21.2% of the placebo group (p = 0.38)
  • Heart failure hospitalization: 27.4% of the vericiguat group compared with 29.6% of the placebo group (p = 0.048)
  • Serious adverse event: 32.8% of the vericiguat group compared with 34.8% of the placebo group

Hemoglobin and clinical outcomes:

  • Occurrence of new anemia: 13.6% with vericiguat compared with 10.5% with placebo (p < 0.001)
  • Among those with hemoglobin ≤15 g/dl, there was increasing risk for the primary outcome with a lower hemoglobin (HR 1.15 per 1 g/dl hemoglobin decrease)
  • However, the relationship between vericiguat compared with placebo and the primary outcome was preserved, when hemoglobin was added as a time-dependent variable (hemoglobin <15 g/dl, p for interaction = 0.104)


Among patients with CHF with recent decompensation, a novel strategy of increasing soluble guanylate cyclase activity with vericiguat was effective. Vericiguat compared with placebo was effective at reducing cardiovascular death or hospitalization for heart failure. There was a possible enhanced benefit among patients <75 years of age. There was no apparent reduction in all-cause mortality with vericiguat compared with placebo. Vericiguat was safe and well tolerated and did not require monitoring of renal function or electrolytes. Vericiguat may represent a novel treatment among patients with recent heart failure decompensation. Vericiguat was associated with new anemia; however, the benefit of vericiguat compared with placebo on prevention of adverse events was preserved when hemoglobin was considered in a time-updated model.


Ezekowitz JA, Zheng Y, Cohen-Solal A, et al., on behalf of the VICTORIA Study Group. Hemoglobin and Clinical Outcomes in the VerICiguaT Global Study in Patients With Heart Failure and Reduced Ejection Fraction (VICTORIA). Circulation 2021;Aug 25:[Epub ahead of print].

Armstrong PW, Pieske B, Anstrom KJ, et al., on behalf of the VICTORIA Study Group. Vericiguat in Patients With Heart Failure and Reduced Ejection Fraction. N Engl J Med 2020;382:1883-93.

Editorial: Burnett JC Jr. Vericiguat — Another Victory for Targeting Cyclic GMP in Heart Failure. N Engl J Med 2020;382:1952-3.

Presented by Dr. Paul W. Armstrong at the American College of Cardiology Virtual Annual Scientific Session Together With World Congress of Cardiology (ACC 2020/WCC), March 28, 2020.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: acc20, ACC Annual Scientific Session, Atrial Fibrillation, Blood Pressure, Diuretics, Geriatrics, Guanosine Monophosphate, Heart Failure, Hemoglobins, Natriuretic Peptide, Brain, Peptide Fragments, Secondary Prevention, Stroke Volume, Vascular Diseases

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