VICTOR Trial Results: Vericiguat Efficacy and Safety Across Baseline Background Therapy in Contemporary Ambulatory Patients With HFrEF

Dr. Ezekowitz: 
Hi from HFSA 2025 live here in Minneapolis,I'm Dr. Justin Ezekowitz from the University of Alberta in Edmonton, Canada, and today I'll be reviewing data regarding the efficacy and safety of vericiguat across baseline background medical therapy in contemporary ambulatory patients with heart failure with reduced ejection fraction.

By way of background, the VICTOR trial was a double-blind, placebo-controlled, randomized clinical trial testing whether or notvericiguat versus placebo reduced cardiovascular death or heart failure hospitalization in patients with HFrEF. 

Sofirst of all, we were very curious as to how vericiguat performed on top of excellent background medical therapy. We looked at the background medical therapy by assessing each medication by the modified Heart Failure Collaboratory score, which assigns a point for all of our usual GDMT and assigns a point of 0, 1, or 2 and then totals that to give a total out of a 100%, with a 100% being the best medical therapy and 0 being not on any of those.

Now when we looked at the background medical therapy at the first publication of VICTOR trial, we already knew the medical therapy was excellent. But when we broke this down by the score, we first identified that about a fifth of patients had a score of less than 50. So not on great therapy, but okay therapy.

About another third had the breakdown about 50 to 70. Sothey're on good medical therapy, but not optimal. And about another third more had a score of over 70, as in they had really good medical therapy that would be considered to be optimal. When we looked at the outcomes, looking acrossthe trial, we found that the score somebody has on the modified HFC score, or Heart Failure Collaboratory score, was linked to cardiovascular death or heart failure hospitalization, as well as just straight-up cardiovascular death and all-cause mortality.

So a lower score indicated that people who were not on adequate therapy had a higher rate of bad events. And conversely, if you're on good medical therapy,had a lower rate of events, but you're still having events. Now, when we broke that down between vericiguat versus placebo, we found that the results of the overall trial were concordant across the entire spectrum of medical therapy.

That is, people who are not on great therapy, the midrange, and on adequate medical therapy, were really having the same outcome on vericiguat when compared to placebo. And this was concordant across all the different primary and secondary outcomes we looked at. Now we looked at this in a couple of different ways, but we really wanted to look at it across the entire spectrum.

And the bulk of patients who are really in the trial, it does look like the VICTOR trial on top of this excellent medical therapywe've already seen, we had a good penetration of the medical therapy. But on top of that, vericiguat was better than placebo. And soI think we really want to make sure that we consider overall where does vericiguat play a role in our current armamentarium?

So key takeaways, vericiguat on top of best medical therapy reduced the overall cardiovascular death and all-cause mortality. And I think that's the fundamental primary takeaway we take from the VICTOR trial. 

Thanks very much and live from HFSA, I'm Dr. Justin Ezekowitz, and thank you again for listening.