VERICIGUAT (VERQUVO®)


















VICTORIA Study - Vericiguat vs Placebo in Heart Failure with Reduced Ejection Fraction, NEJM (2020) [PubMed abstract]
  • The VICTORIA study enrolled 5050 patients with NYHA class II - IV heart failure and an ejection fraction < 45%
Main inclusion criteria
  • NYHA class II - IV heart failure
  • Ejection fraction < 45%
  • NT-proBNP ≥ 1000 pg/ml (sinus rhythm) , ≥ 1600 pg/ml (A fib)
  • Hospitalization for HF within 6 months or outpatient IV diuretics
Main exclusion criteria
  • SBP < 100 mmHg
  • Long-acting nitrate use
  • Phosphodiesterase type 5 inhibitor use
  • Implantable left ventricular assist device
Baseline characteristics
  • Average age 67 years
  • Average ejection fraction - 28.9%
  • Median NT-proBNP - 2816 pg/ml
  • Average SBP - 121 mmHg
  • NYHA class: II - 59% | III - 39.7% | IV - 1.3%
Randomized treatment groups
  • Group 1 (2526 patients) - Vericiguat with a target dose of 10 mg once daily (median dose in trial was 9.2 mg)
  • Group 2 (2524 patients) - Placebo
  • Vericiguat was started at 2.5 mg once daily and the dose was doubled every two weeks as tolerated to a target dose of 10 mg
  • 60% of patients in both groups were taking concomitant triple therapy (ACE/ARB + Beta blocker + Aldosterone antagonist)
  • 15% of patients in both groups were taking concomitant sacubitril–valsartan (Entresto)
Primary outcome: Composite of death from cardiovascular causes or first hospitalization for heart failure
Results

Duration: Median 10.8 months
Outcome Vericiguat Placebo Comparisons
Primary outcome 35.5% 38.5% HR 0.90, 95%CI [0.82 – 0.98], p=0.02
Death from cardiovascular causes 16.4% 17.5% HR 0.93, 95%CI [0.81 – 1.06]
Hospitalization for heart failure 27.4% 29.6% HR 0.90, 95%CI [0.81 – 1.0]
Overall mortality 20.3% 21.2% HR 0.95, 95%CI [0.84 – 1.07], p=0.38
Symptomatic hypotension 9.1% 7.9% p=0.12
Syncope 4.0% 3.5% p=0.30
Anemia 7.6% 5.7% N/A
Change in hemoglobin at 16 weeks -0.38 g/dl -0.14 g/dl N/A

Findings: 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 among those who received placebo.