VICTORIA Trial: Vericiguat Reduces Rates of Cardiovascular Death or Hospitalization Due to Heart Failure in Patients with Heart Failure

Fahad Alkhalfan, M.D.
By Fahad Alkhalfan, M.D. on

The results of the VICTORIA trial were presented at the American College of Cardiology 2020 Meeting and simultaneously published in the New England Journal of Medicine. The trial demonstrated that vericiguat, an oral guanylate cyclase stimulator, decreased the occurrence of death from cardiovascular cause or hospitalization for heart failure in patients admitted with high-risk heart failure.

Heart failure with reduced ejection fraction (HFrEF) continues to place a significant burden on the current healthcare system. vericiguat, a novel oral guanylate cyclase stimulator, was previously shown to reduce the level of N-terminyl pro-B-type natriuretic peptide (NT-pro BNP). In this trial, the investigators aimed to assess the efficacy and safety of vericiguat in patients with HFrEF.

The VICTORIA trial was a multi-center randomized controlled trial that enrolled patients with chronic heart failure (NYHA classification 2-4) and reduced left ventricular ejection fraction (less than 45% within the last 12 months), and an elevated natriuretic peptide (within the last 30 days). Additionally, patients needed to demonstrate evidence of worsening heart failure. Patients were split into three categories based on the timing of deterioration: (1) Hospitalization within 3 months before randomization; (2) Hospitalization 3-6 months before randomization; (3) Requiring the use of intravenous diuretic therapy without hospital admission in the three months prior to randomization. Patients were randomized in a 1:1 ratio to either 2.5mg of vericiguat or placebo. Doses were increased up to 10mg based on the clinical situation and the patient’s blood pressure. The primary outcome of the study was a composite of death from cardiovascular causes or first hospitalization for heart failure.

A total of 5,050 patients were included in the study (2,526 patients to vericiguat and 2,524 patients to placebo). The mean age was 67, 24% were women, 66.9% were hospitalized for heart failure within the last 3 months, 59.0% were NYHA 2, 39.7% were NYHA 3, and 1.3% were NYHA 4. Additionally, the mean ejection fraction at time of screening was 28.9%. The composite outcome occurred in 35.5% of patients in the vericiguat group and 38.5% of the placebo group (HR 0.90, 95% CI 0.82 – 0.98, p = 0.02). Death from cardiovascular causes occurred in 16.4% in the vericiguat group and 17.5% in the placebo group (HR 0.93, 95% CI 0.81 to 1.06). Additionally, 27.4% and 29.6% of patients in the vericiguat group and placebo groups were hospitalized for heart failure (HR 0.90, 95% CI 0.81 to 1.00). With regards to the safety profile of the drug, symptomatic hypotension occurred in 9.1% of patients in the vericiguat group and 7.9% of patients in the placebo group (p = 0.12). Syncope occurred in 4.0% and 3.5% of patients in the vericiguat group and placebo group respectively (p = 0.30).

In an interview with Dr. C. Michael Gibson, Dr. Carolyn Lam, one of the investigators in the study, discussed the results of the study. She noted, “with such a high event rate, to even just impact that, or move the needle just a little bit in terms of relative risk reduction, vericiguat reduced the relative risk by 10%, but that 10% translated into a huge absolute risk reduction and that was a 4.2% absolute risk reduction which then translates to a number needed to treat of only 24 over a year. If we look at it that way, we have not had such a big winner in such a big population and we really need the winner. It was also very reassuring to know that this was a drug that was very well tolerated, more than 90% of everyone reached a target, it’s a once daily oral medicine, and it appeared safe, with a little bit more hypotension and syncope. In general, you don’t need to monitor it and you can use it down to an EGFR of 15, and it seems to help this really sick population.”

Click here to listen to the discussion between Dr. C. Michael Gibson and Dr. Carolyn Lam.

Leave a Reply