An extension of the study showed sacubitril/valsartan's benefit as an initial hospitalized heart failure therapy.
Following the presentation of PIONEER-HF trial data the American Heart Association (AHA) 2018 Annual Meeting in Chicago last November, investigators shared new 12-week open label extension data at the American College of Cardiology (ACC) 2019 Annual Scientific Session in New Orleans, LA, this week.
The data built upon the promising findings of sacubitril-valsartan as a beneficial therapy for patients hospitalized with acute decompensated heart failure with reduced ejection fraction (HFrEF) versus enalapril and added fodder to the idea of using the former therapy as an initial hospital treatment.
In an interview with MD Magazine®, study presenter Adam DeVore, MD, assistant professor of Medicine, Duke University, explained how the extension data built on the original study, and what the continued improved outcomes mean for the prescribing physician.
MD Mag: What were the findings of the 12-week PIONEER-HF hospitalization analysis?
DeVore: I had the pleasure of presenting the PIONEER-HF open-label extension study today, and I think to put them in context, it’s helpful to remember back to what the primary results of the PIONEER-HF study was. That was released last fall and published in the New England Journal of Medicine. And the study was a randomized trial of 881 patients all in the hospital with acute heart failure, and they all had a low ejection fraction of 40% or less. And we enrolled them at some point where they had achieved hemodynamic stabilization. Then we randomized them to either sacubitril/valsartan or enalapril, and continued that to the next 8 weeks.
In that study, what we learned were really 3 things. One, we learned that was well-tolerated. You know, there's some concern that when people are in the hospital, still getting diuretics, that starting new medicines might be unsafe in their blood pressure too. And it was very well tolerated—exactly the same in both arms.
The second thing we learned was that there was a dramatic drop in N-terminal pro—B-type natriuretic peptide (NT-proBNP), an important biomarker in heart failure. It seemed like it was having an important physiologic effect, and it dropped quickly in the hospital in the weeks that followed compared to the enalapril arm. And that was the primary result of the study.
The other thing we learned though, is that even in only 881 patients, we saw a really important finding of improved clinical outcomes—mainly reduced heart failure rehospitalizations, which is a really important thing in the heart failure field.
So that was the original PIONEER-HF trial and that trial was 8 weeks long. What we did was another 4 weeks where we gave everybody sacubitril/valsartan, regardless of what they were randomized to at the beginning.
What will prescribing physicians take away from these findings?
So, the reason we did the open-label extension study was to try to learn 2 things, and I think both of them are relevant to clinical practice—especially the second one.
So, the first reason we did this was because we are trying to understand in those patients who had 8 weeks of the enalapril and got switched to sacubitril/valsartan what happened to their NT-proBNP levels. And what we saw was a very rapid drop. So, even over only 4 weeks, there was a 36% decline in their NT-proBNP levels, and we know that's really important prognostically for how patients are going do in heart failure.
The second thing we learned is that we now have a cohort of 880 patients that have been treated for 12 weeks. Some of them got sacubitril/valsartan early in the hospital, and the other ones had enalapril and delayed sacubitril/valsartan. And if you step back and said, “Which strategy was more effective?,” it’s a very common clinical scenario: should I start this medicine in the hospital, or should I just wait until I see him in clinic?
It seemed like there was a really a missed opportunity for the patients that started on the enalapril and got switched later in the course of their heart failure journey. There was a 33% reduction in this composite endpoint of death, heart failure rehospitalization, or L-VAT implantation.
So I really think it’s a clinically important finding that translates into everyday practice, because it's such a common condition.
The study, “Initiation of Angiotensin-Neprilysin Inhibition after Acute Decompensated Heart Failure: Results of the Open-Label Extension of the PIONEER-HF Trial,” was presented at ACC 2019.