The latest real-world clinical practice data from the VICTORIA trial of vericiguat bolster previous data on the medication’s benefit by showing that 92% of patients hospitalized for a worsening heart failure event would be eligible to start the therapy and that doing so would reduce their risk of heart failure hospitalization and cardiovascular death, noted Stephen J. Greene, MD, Duke University Medical Center and the Duke Clinical Research Institute.
The latest real-world clinical practice data from the VICTORIA trial of vericiguat (Verquvo), a soluble guanylate cyclase stimulator, bolster previous data on the medication’s benefit by showing that a high share, 92%, of patients hospitalized for a worsening heart failure event would be eligible to start the therapy and that doing so would reduce their risk of heart failure hospitalization and cardiovascular death, noted Stephen J. Greene, MD, heart failure cardiologist at Duke University Medical Center and the Duke Clinical Research Institute.
On day 2 of the American Heart Association Scientific Sessions, he presented, “Generalizability of the Victoria Trial and the US FDA Label for Vericiguat to Patients Hospitalized for Heart Failure With Reduced Ejection Fraction in the United States,” during the Drugs, Drugs and More Drugs in Heart Failure: Impact on Outcomes session.
How do the new VICTORIA data build on results presented last year and during the American College of Cardiology’s spring meeting?
The VICTORIA trial showed that a novel therapy called vericiguat reduced the risk of heart failure hospitalization and cardiovascular death among patients with a worsening heart failure event. But that's a randomized clinical trial. And the next question people often have is, “Well, how do those patients translate to real-world clinical practice?” So that was kind of the key construct for this analysis, where we wanted to see the eligibility criteria in the VICTORIA trial, as well as the eligibility criteria based on the recent FDA label for vericiguat, how those criteria applied to real-world clinical practice patients that you see. Again, how much it was the scope of those trials can apply to the patients we see every day.
What are the benefits of starting heart failure therapy in the hospital?
With multiple different therapies that we've studied, real-world evidence strongly supports the benefits of in-hospital initiation of therapy. One, the hospitalized patients are patients at highest risk; they need all the help they can get. So we need to give them every opportunity to benefit from a therapy. But two, we know that deferring in-hospital initiation is unfortunately associated with either never initiating the therapy as an outpatient or at best substantial delays. So combining the risk that these patients inherently have by being hospitalized heart failure patients with the risk of delaying the initiation of these effective therapies, time in, time out, we've seen in-hospital initiation the strongest strategy for implementation.
What are some postdischarge reasons preventing therapy initiation?
We know both in the outpatient and inpatient setting, there's strong suggestion of what I call clinical inertia toward GDMT [guideline-directed medical therapy]. Whether it's in the hospital and we have a diurese-and-discharge mentality or in the outpatient setting where people come time after time to the outpatient clinic yet have very to no minimal changes in their GDMT. I think it's because we don't understand how high-risk heart failure patients really are.
In both inpatient and outpatient datasets, the patients we’ve seen have blood pressures of 120 mm Hg. On median, they have GFR [glomerular filtration rate] is in the 50s or 60s—so strongly suggesting there's ample room to escalate GDMT. Then we see the gaps that we see with GDMT, and you have therapies like MRA [mineralocorticoid receptor antagonists] therapy where 2 out of 3 eligible patients are not receiving therapy. We have similar gaps in beta-blockers, ACE [angiotensin converting enzyme inhibitors], ARB ]angiotensin receptor blockers], ARNI [angiotensin receptor/neprilysin inhibitor]. Really across the board there's huge underutilization under dosing of GDMT despite the risk that these patients face
Does the sum of the findings on vericiguat suggest there are cost savings and other benefits to be achieved with broader use?
We clearly show in this analysis that the patients eligible for vericiguat, whether you look at the FDA label or the actual VICTORIA trial criteria, the patients eligible for vericiguat faced high risk of postdischarge death and hospitalization and they also accrue substantial postdischarge health care costs. There's clear burden, both economic and public health wise, these patients face, so they need all the help they can get. And I would argue that includes maximizing use of quadruple medical therapy for heart failure, but also strong consideration for vericiguat to further reduce residual risk in this very-high-risk patient population.
What are major barriers to uptake of vericiguat?
I think it relates to what I was saying earlier about just underappreciation of what the risk is like for these heart failure patients. You have a very, very-high-risk condition, yet you have very, very low use, relatively speaking, of guideline directed medical therapies proven to lower that risk. And I think it comes down to this complacency that the patient is stable or they feel well today. Yet we don't understand there's no such thing as a low-risk heart-failure patient, there’s no such thing as a stable heart failure patient. The term high risk doesn't even do justice [to the risk] that these patients have. Most of them, especially patients with worsening heart failure, you look at their absolute risks of death, hospitalization, I would classify them at very extreme, high risk, extreme risk.