Should Heart Failure Drug Natrecor Be Recalled Due To Safety Questions?

Citing Lack Of Safety Studies, Dr. Eric Topol and Others Want FDA to Recall Natrecor

In May 2005, the publication of two medical journal articles linking Natrecor to kidney problems higher death rates than standard heart failure treatments gave rise to a growing controversy about the safety of Natrecor.

A July 14, 2005 article by renowned cardiologist Eric J. Topol, M.D. entitled "Nesiritide -- not verified" in the The New England Journal of Medicine prompted letters to the editor supporting and disputing Dr. Topol's concerns. The letters were published, along with replies, in the NEJM's October 6, 2005 edition.

One such reply in the October 2005 NEJM, was a letter to the editor co-authored by Jonathan Sackner-Bernstein, M.D. and Keith D. Aaronson, M.D. This letter supported Dr. Topol as concerns his Natrecor article, and in their letter Dr. Sackner-Bernstein and Dr. Aaronson called for a Natrecor recall:

"Although controlled trials demonstrate that [Natrecor] reduces symptoms of dyspnea and lowers pulmonary-capillary wedge pressure, no clinical trial has demonstrated that [Natrecor] is safe in patients with acute decompensated heart failure who have dyspnea at rest or on minimal exertion. To be consistent with federal regulations addressing the basis for drug withdrawal [footnote omitted], the FDA can and should withdraw approval for the marketing of [Natrecor]. At a minimum, an advisory panel to the FDA should address these issues in a public forum."

In the same NEJM edition was a separate letter to the editor written by George Schreiner, M.D., of Scios, who took issue with Dr. Topol's Natrecor article. In relevant part, Dr. Schreiner asserted:

"[Natrecor] is the only treatment for acute decompensated heart failure that has been proved in controlled clinical trials to provide a clinical benefit — improvement of dyspnea.... Safe and effective when used as labeled, [Natrecor] continues to be an important therapy for acute decompensated heart failure."

In the same October 6 NEJM edition, Dr. Topol was permitted an opportunity to comment on these two letters to the editor as well as his earlier Natrecor article. In his reply Dr. Topol joined Dr. Sackner-Bersnstein and Dr. Aaronson in calling for a Natrecor recall:

"Beyond the serious questions about [Natrecor] safety, there have been no trials to demonstrate clinically meaningful efficacy. This would require a reduction of death or repeated hospitalization for heart failure at 30 days, and such a trial has not been initiated, despite the drug having been approved more than 4 years ago. Clearly, the minimal criteria for safety and efficacy have not been fulfilled, and I agree that drug withdrawal, until such time validation is assured, is a reasonable proposition."

And what does the FDA have to say about the growing Natecor safety controversy? In late 2005 Dr. Robert J. Temple, the FDA's associate director of medical policy, said that the FDA had not received any new information on Natrecor that would cause the agency to revisit its 2001 decision to approve Natrecor, i.e., highly unlikely that the FDA will recall Natrecor.

The FDA position statement by Dr. Temple did not surprise Dr. Topol, who has publicly expressed doubt that the FDA will order a Natrecor recall:

"With all the leadership strife at FDA and the unwillingness of those people who were involved to admit the potential of being too lenient [in approving the drug], I'm not optimistic."

Meanwhile, the controversy about Natrecor's safety continues -- as does the government's investigation into the Natrecor "off-label" prescribing issue.

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