Nesiritide: Bad news from JAMA

Again, never be the first, and never be the last to use a new drug.  Looks like the jury’s still out on this one.  Here’s some of a review from Medscape about today’s JAMA article (emphasis added):

April 20, 2005 ? The bad news is getting worse regarding the
natriuretic nesiritide (Natrecor)
, a medication with both diuretic and
vasodilatory properties that is often given in the treatment of acute
exacerbation of decompensated heart failure.

Earlier research had shown that nesiritide, despite claims, is not
associated with preservation of renal function. Now, in a meta-analysis
published in the April 20 issue of JAMA, investigators report
that patients treated with nesiritide are more likely to die in the 30
days after treatment than are patients treated with noninotrope
therapies used in acute congestive heart failure.

The investigators found that
nesiritide-treated patients were 1.74 times more likely to die
within
the 30-day window. Among the nesiritide-treated patients, 35 (7.2%)
died in this time period compared with 15 (4.0%) of those treated with
other medications (P = .059). After adjusting for different variables, the risk of death in the nesiritide group increased slightly to 1.80 (P = .057).

And, it turns out it isn’t completely unexpected:

"These results were disappointing but not surprising," Stephen A.
Siegel, MD, said in a phone interview. Dr. Siegel, who was not involved
in the study, is a clinical assistant professor of medicine in the
division of cardiology at the New York University School of Medicine in
New York City.

"The inotropic support concept has never worked," Dr.Siegel pointed
out. "It’s paradoxical, because if the heart is lacking contractility,
it would make sense to give a medication that increases contractility.
However, this treatment approach doesn’t seem to reduce the risk of
death."

Dr. Siegel concluded, "It may be that we need to explores other ways
to treat congestive heart failure, such as the neuronal-hormonal
effect. The definitive answer of how to treat it hasn’t been identified
yet, but considering that inotropes don’t work, this drug class just
may be the wrong way to go."

JAMA. 2005;293:190-195    By

  Paula Moyer, MA Freelance Medical Writer

This drug has never caught on in our ED, and when used it’s been at the behest of the cardiologist who admits the patient.  Given this, I don’t see that changing.


Comments

  1. It’s qite disapointing. My experience with the drug is that it does wonders to diures patients, especially those who demand lack response to lasix. The main problem I’ve always contemplated is: Where do you go from there? You can’t keep the patient on Niseritide forever.
    Although, I’ve heard of patients getting PICCs and going home for continual Niseritide infusions for life. (Or the rest of theirs)

  2. Alice Lee, MD says:

    I’m so glad this news is out. We’ve never endorsed Natrecor in our ED despite what cardiologists and even the medical staff director wanted. As a group, we don’t buy into what the drug reps peddle as scientific proof of efficacy no matter how many free dinners they invite us to. We found through chart reviews in our hospital that medical management of acute CHF in the ED and in-house was inconsistent. Use of inexpensive and standard treatments was not being optimized thus it appeared to some the new kid on the block was more efficacious. We felt that if we standardized CHF care first, then if that failed, Natrecor could be recruited as a secondary treatment. Now, it appears from this new article that there is actually detrimental effects of it’s use.

  3. Used it, worked on about half the patients that didn’t diurese with conventional therapy. It was defintely a second-line therapy, not for ED use – doesn’t work fast enough, either for diuresis or SOB symptoms, and it’s damn spendy – to be the primary tool on anybody’s belt.

  4. mark Rabold says:

    Gentlemen there is WAY more to this story. It is my understanding that this “study” used unfair and unethical methodology published by a consultant of a rival new drug to nesiritide. HUGE conflict of interests here. This study came out the SAME day as a the new package insert published by the FDA who never even mentions mortality.

  5. GruntDoc says:

    Umm, Mark, Details? From my reading of the abstract it looks pretty good. I don’t have full text available to read the physicians’ statements of conflicts.

  6. mark Rabold says:

    I was informed by a fellow ER doc buddy of mine of some of these back room details. Essentially the data, he says, was compiled to cast the most negative possible light on nesiritide while more “friendly” data was ignored and so thus of poor methodology. Of course, my buddy is a consultant for Nesiritide and so one might argue that he is biased as well. Could well be. My response was to inform readers of a possible conflict of interest and ethic problem in this study. Things are not always as they seem. I am NOT a huge fan of nesiritide. I have used it maybe 7-8 times with variable results. The only BIG advantage I can see is that if your hospital protocols allow it to be used outside the ICU, then huge amounts of money can be saved keeping those folks who are usually on nitro and/or dobutamine drips out of the expensive ICU and decreasing length of stay. Personally I have had to discontinue it 30-40% of the time because of hypotension. Anyway, no matter who is right, it was an interesting look into the drug business

  7. In heart failure you don?t see anything really new for years…The neurohormonal theory works but we reach its limits years ago. Your patients finally dies….Like all of them, of course :-)

  8. On behalf of my co-authors, we are pleased to see ongoing discussion about nesiritide. I will start by pointing out that the analyses (Circulation March 2005 and JAMA April 2005) are based on the most complete review of all of the data from all of the studies performed by Scios/J&J. The papers detail the selection bias and provide the URLs where anyone can download all of this data and see for themselves that the strong associations between nesiritide use and risk are very strong, clinically relevant and most notably, quite disturbing since all these data were available since 2002. We contacted Scios in the Spring of 2002 when we first reviewed these data, so they definitely knew all about it. Still, they have done nothing to formally investigate the safety of nesiritide in double-blind prospective mortality trial.

    Now about the behind the scenes story, there is none. All is up front. None of the authors have relationships of any kind with any rival company or drug. This information was relayed to me by a reporter who covered the first publication, and it is an outright lie. That’s the level to which people have tried to hide from the truth.

    Nesiritide has been shown to reduce symptoms of dyspnea compared to a placebo, but what hasn’t been pointed out is that in that study (VMAC), people getting nesiritide did not rate their over all well being as different than those patient getting the placebo. And the study showed no difference in symptoms between nesiritide and nitroglycerin. Balance these “benefits” against the risk of worsening renal function and death and the equation is pretty simple.

    Why are people trying to stir up a story to undermine the scientific integrity behind our analyses? Because they are scared to admit that they behaved irresponsibly by ignoring a risk that was evident since 2002. None of the ongoing trials is designed in a way that will enable them to show the drug is safe. All they will do is distract us from the data that says the drug is likely to be dangerous.

    Next time someone says it’s a good idea to use the drug, remember that it is also true that Vioxx reduces pain.

  9. What’s new in this story?
    Any change?
    Vlad

  10. No change that I’m aware of.