Dr. Clyde Yancy on Recent Heart Failure Studies

Melissa Walton-Shirley, MD; Clyde W. Yancy, MD, MSc


February 24, 2014

In This Article

Nesiritide: A Drug Looking for a Home

Dr. Walton-Shirley: Patient selection is everything.

I wanted to switch gears to ROSE AHF[2] now. Just to recap, this was 360 patients, dopamine and nesiritide vs placebo. There was no difference in outcomes at 2-6 months.

My first question is, was 2 µg/kg/min too little? I have up-titrated those patients many times and thought that I was getting appropriate diuresis. How do you feel about that?

Dr. Yancy: I am glad that they did this study, because many of us have used some heuristic logic to help us believe that giving low doses of dopamine would improve renal perfusion, and we have also been able to deduce from reasonable science that previous administrations of nesiritide were at too high a threshold and a lower dose might be sufficient to augment or expose the renal benefits of natriuretic peptides given pharmacologically. Neither of those sets of logic held true in this trial. Diuretic therapy seemingly prevailed, or at least was as good.

I think we look at this and say, this is why we do clinical trials -- because as practitioners at the bedside who want to help our patients, we will extend some of the things we know because we want to help, and so we will use agents that we think, hope, maybe pray will help a patient who has acute heart failure do better. We have to do these kinds of trials to inform our decision-making, so I'm back at the same point. I don't look at ROSE AHF as a positive or a negative study. I look at it as an informative study -- an important study, because it tells us that we should pause a moment and understand whether it is really the right next thing to do to give a low dose of dopamine or an ultra-low dose of nesiritide to a patient with diuretic resistance. It may be that the diuretics are still the best therapy, albeit an imperfect therapy. That may be what it is.

Dr. Walton-Shirley: I thought it was remarkable in this trial that 5%-10% of US hospitals still use nesiritide. In your opinion, is there any benefit or any place for nesiritide in the patient's armamentarium of medications?

Dr. Yancy: In the guidelines that we just released, the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines[3] addressing heart failure, we incorporated a section on hospitalized patients and took a de novo look at all the data. Once again, we reached the conclusion that if in the clinician's judgment a vasodilator would be appropriate for a patient with decompensated heart failure, then there are 3 choices -- nitroprusside, intravenous nitroglycerin, and nesiritide -- and the practitioner is given the latitude, if you will, to make that decision. That is the only indication we have, but it is not an overwhelming indication. It is a relatively soft indication, but outside of that, this continues to be a drug looking for a home.

Future Therapies for Heart Failure

Dr. Walton-Shirley: Just to wind up, and leaving AHA 2013, as one of the world's foremost practitioners of heart failure management, what do you see in the next 2 or 3 years that really piques your interest? What are you waiting for?

Dr. Yancy: I'll give you 2 answers. What I see that piques my interest is redoubled efforts at prevention. Even though we have come a long way and have many great drugs and devices, it's still a disease that carries a lot of heft in terms of morbidity and mortality. Coming back to the front side and thinking about prevention is the opportunity. That's the bonanza in this space, because more and more people are developing heart failure, and as we continue to focus on the back end and trying to come up with the right idea, don't forget about the front end: cutting off the faucet.

I am hopeful from a therapeutic side, going forward, for some opportunity to incorporate regenerative therapies. I don't know how far off that is. Maybe 3 years is too short a window, but there is so much exciting work going on with regenerative therapies, different kinds of regenerative cell lines, and different kinds of delivery systems, that we have to hit some area of success here soon. That really would be the ultimate game changer here, so that we could regenerate myocardium and do it safety and effectively. We only need a little boost. We don't need to make it normal again -- just a little boost --so let's see what happens.

Dr. Walton-Shirley: That's great, and I think we all agree that where there is interest and motivation, there is hope. Thanks so much for joining us today and thank you for joining us on on Medscape.


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