Emerging Agents for Heart Failure Treatment

James Januzzi, MD: Javed, the last couple of points I’d like to touch on before we close speak in part to the continued development of the space. There are a couple of therapies that you mentioned earlier that I’d like you to give a 30-second bullet on for each, which includes vericiguat and intravenous [IV] iron. In the landscape of therapies for our patients with heart failure with reduced EF [ejection fraction], where do these fit in? Do they fit in at this point? Where do you see them going in the future?

Javed Butler, MD, MPH, MBA: Think about the journey of patients with heart failure. You have no heart failure, then you develop heart failure and you’re not on any therapy, so the risks are pretty high. Then you get started on the standard therapy and the risks come down—what we call residual risk—but it’s never back to not having heart failure. Then you start breaking through, you start developing worsening symptoms. Whatever therapy you were taking that kept you stable as an outpatient is not enough anymore. That is now an entity we call worsening heart failure.

We did the VICTORIA trial on vericiguat that had a positive result on the cardiovascular death and heart failure hospitalization primary end point. It was focused on people on standard therapy who developed worsening heart failure, either recent hospitalization or the need for outpatient IV diuretic. That therapy is now approved by the FDA for ejection fraction less than 45% and recent worsening heart failure because of improvement in cardiovascular death and heart failure hospitalization. Whether it should be given to people without worsening heart failure is something we are all questioning. Let’s see if we can generate some evidence.

I really like IV iron because this is a specific disease within heart failure that you’re treating. Iron deficiency should be in our minds dissociated from anemia. There are other causes of anemia, but iron deficiency, regardless of anemia, is associated with worse outcomes. Anemia reduces oxygen carrying capacity, but iron is also needed for ATP [adenosine triphosphate] generation in the mitochondria. You can have reduced energy production, regardless of anemia, as well. We had a lot of trials in the outpatient setting showing in the past that iron-deficient patients given IV iron improve quality of life and functional capacity. Now we have a 1-year outcomes trial called AFFIRM-AHF. When patients in the hospital setting with iron deficiency are given iron, you reduce the risk of rehospitalization in those patients. This was an outcomes trail, and not only a quality of life and functional capacity trial.

James Januzzi, MD: In whom would you suggest IV iron be considered? Can you give us a transferrin saturation number?

Javed Butler, MD, MPH, MBA: Yes. There is an issue of absolute iron deficiency or relative iron deficiency. If a patient has a transferrin saturation of less than 20%, that’s a good patient to get iron. But remember that oral iron therapy, unfortunately, does not get absorbed very well, so you have to give IV.

James Januzzi, MD: Yes, I was going to actually ask, “Why don’t we just throw some iron sulfate into the medical program?” You just jumped ahead of that question. It’s a really important consideration that clinicians need to know, in part because patients with heart failure don’t absorb PO oral iron as well due to abnormalities of hepcidin.

I’m going to draw this to a conclusion and try to appeal to our viewers, which include a large number of community physicians, to remember that heart failure is a team sport. We need to work together in understanding how to identify these patients, how to initiate therapies, when to initiate therapies, and when to reach out for help. In the expert consensus document, I would ask you to have a look at 1 specific figure that focuses on recognizing heart failure, initiating the therapies, but then recognizing when patients are not responding and where you might need to kick it up a notch and refer to a heart failure specialist like Dr Butler.

There’s a simple acronym called I-NEED-HELP. Each letter refers to a different aspect of struggles in heart failure care that might help you recognize when to reach out to an advanced heart failure specialist. Not every patient with heart failure can be treated by a heart failure transplant specialist. The care of our patients most in need to reduce their risk for heart failure events is in your hands. The American College of Cardiology and the development of this expert consensus decision pathway document recognizes that. In addition to the document, there’s a smartphone application called TreatHF that summarizes all of the things that we just talked about in terms of the therapies, how to use them, when to use them, how to troubleshoot adverse effects, and other issues that come up in the course of the care of our patients with heart failure. It’s all in your hands, folks. We hope that the document is as useful to you as it is for us. Dr Butler and I both find it to be a really helpful piece of support for the care of our patients. 

I want to thank you all for watching HCPLive® Peers and Perspectives®. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peers and Perspectives® and other great content right in your inbox. Javed, thanks so much for spending time today.

Javed Butler, MD, MPH, MBA: Great talking with you, Jim.

James Januzzi, MD: You as well. Thanks.

Transcript Edited for Clarity