Hi, I'm Dr. Javed Butler. I'm a cardiologist and a clinical trialist with Baylor Staunton White Health in Dallas and professor of medicine at University of Mississippi. And today I will talk to you about the pooled analysis between the VICTORIA and the VICTOR trial which was presented here in the late breaking clinical trial session at ESC 2025.

What is the current research landscape for vericiguat treatment for HFrEF, and what was the reasoning behind the study?
We know that the VICTORIA trial showed a couple of years ago that patients with heart failure with reduced ejection fraction and a recent worsening heart failure event which was described as either hospitalization for heart failure within the past six months or need for allocation of IV diuretic within the past three months. In those patients the use of vericiguat was associated with improvement in cardiovascular death or heart failure hospitalization. VICTOR trial was done to look at now the rest of the spectrum of HFrEF patient, that is those patients without worsening heart failure ambulatory patients. Those results were also presented and this particular pre specified pooled analysis was to look at the picture the entire spectrum of heart failure by combining the VICTOR and the VICTORIA databases together.

What was the study design and patient population?
This was a pre-specified individual patient level pooled analysis of the two studies. Here we combined first the entire spectrum of patients with the entire severity of the disease state. But then also we learned in the VICTORIA trial that people with higher NT-proBNP had less benefit. That actually informed the design of the VICTOR trial that included patients with NT-proBNP of only less than 6,000. So we also then did focus analysis of those patients in the combined database with NT-proBNP of less than 6,000. And in this in the two groups of patients, the entire population and Those with NT-proBNP less than 6,000, we looked at four outcomes. We looked at cardiovascular death, all cause mortality, cardiovascular death or heart failure hospitalization and heart failure hospitalization by itself.

What were the key findings?
The key findings for the results were if you look at the entire study population, there was a statistically significant benefit on all four outcomes of approximately 10% relative risk reduction. When we narrow in into the population of Those with NT-proBNP less than 6000, again we found statistically significant benefit but the benefit was even stronger in that group ranging from 5 to 17% relative reduction in that particular group.

What are the take-home messages for practice?
The key take home messages are that one in this combined pool analysis of all patients across the entire spectrum of disease, there was a statistically significant reduction in cardiovascular death, all cause death, cardiovascular death or heart failure hospitalization or first heart failure hospitalization. All four outcomes, all of them were statistically significantly reduced. And the benefits were even more so in those with NT-proBNP of less than 6,000. Combining this with the known safety and tolerability profile of vericiguat, we now have a, yet another therapy to improve outcomes for our patients with HFrEF.

What further research is needed in this area?
The next step, like all things, you have a positive result from any given trial on an outcome is the implementation, because implementation in the real world, there's a lot of inertia, and I think these patients are at a very high risk. So now moving away from evidence generation to evidence implementation, and how quickly can we get the patients who deserve these therapies? And I'm not talking about just one vericiguat, I'm talking about all heart failure therapies, because there's a lot of inertia. I think that's our real challenge now.