VICTOR Trial Results: Regional Variation in Outcomes and Response to Vericiguat in Patients With HFrEF

Dr. Lam:
Hello from Heart Failure Society of America 2025 here in Minneapolis. I'm Dr. Carolyn Lam, and today I will be reviewing data that were presented from the VICTORtrial regarding regional variation in outcomes and response to vericiguat in patients with heart failure and reduced ejection fraction, or HFrEF.

So first, an overview of the primary VICTOR results. VICTOR is a large outcomes trial, phase 3, conducted in more than 480 sites across 36 countries falling into 5 regions. That would be North America, Latin and South America, Eastern Europe, Western Europe, and Asia Pacific. 

Now, we randomized patients with HFrEFwho had not been hospitalized within 6 months or had any outpatient IV diuretics within 3 months, and they were randomized into the arms of oral vericiguat at a target dose of 10 mg a day compared to placebo.

While the VICTOR primary composite endpoint of cardiovascular death or heart failure hospitalization was neutral, there was a signal for benefit in terms of cardiovascular and all-cause death reduction with vericiguat compared to placebo. Interestingly, when worsening heart failure was looked at in totality, including outpatient oral diuretic intensification, on top of heart failure hospitalizations and IV diuretics, there was a signal of benefit with vericiguat.

So in the current analysis looking at regional variation, we really wanted to look at the differences across the region studied in VICTOR in terms of both the baseline rates of heart failure hospitalization and cardiovascular death. In other words, in the placebo arm alone. And then look at the impact of vericiguat considering thatperhaps in the regions with a higher heart failure hospitalization to cardiovascular death ratio, those may be the areas where there may be a greater signal of benefit with vericiguat.

And indeed, what we found was there was regional heterogeneity in the placebo arm of the rate of the primary composite endpoint of heart failurehospitalization and cardiovascular death.

The rates of cardiovascular death were fairly similar across the regions, and the differences were driven by differences in heart failure hospitalization rate. And this is despite being a standardized protocol and despite having similar baseline NT-proBNP. 

Regarding the impact of vericiguat, there appeared to be a stronger signal of benefit in the regions with a higher heart failure hospitalization to death ratio, and that would be North America and the Asia-Pacific regions.Although overall there was no significant interaction between treatment and region. There was a consistent effect of cardiovascular death benefit and all-cause death benefit across all the regions. 

And so I think that the take-home message here is while we examine the benefit of new therapies in HFrEF, we really need to consider the region and the regional practice of heart failure hospitalization in that country.And it's in areas where there's high hospitalization rates that it may be easier to demonstrate the benefit in terms of reduction in hospitalization. 

In other regions, such as in Western Europe where outpatient events played a bigger role, then when we consider the totality of worsening events,it's easier to demonstrate the benefit of vericiguat. And regardless of all this, across all regions, there is a strong signal of benefit in terms of survival, cardiovascular death, and all-cause death were reduced.So these I think should be borne in mind as we look at the clinical implementation of putting all these new signs into practice. 

Once again, from HFSA 2025, I'm Dr. Carolyn Lam. Thank you for listening.