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Nesiritide Increases Mortality If Acute Renal Failure Occurs


 

PHILADELPHIA — Patients with heart failure who are taking nesiritide and who develop acute renal failure may be at an increased risk of death, Dr. Jose Iglesias said at the annual meeting of the American Society of Nephrology.

He presented new data showing that the use of nesiritide in patients with heart failure was not an independent predictor of mortality, but that it may be associated with an increased risk of mortality among patients who develop acute renal failure (ARF) after administration of neseritide.

Nesiritide (Natrecor) fell under scrutiny following the publication in early 2005 of two studies showing that it had no real benefit in heart failure and might increase the risk of death, Dr. Iglesias of the University of Medicine and Dentistry of New Jersey School of Osteopathic Medicine said in presenting two studies on the topic. He conducted the research with associates at his institution, the Community Medical Center of Toms River (N.J.), and the University of Illinois at Chicago.

Both studies looked at patients with heart failure at the Toms River hospital, which admits close to 2,000 patients for that diagnosis each year.

In one study, the researchers analyzed 60-day mortality and ARF risk in 219 consecutive patients who came to the hospital for heart failure, including 71 who were given nesiritide. Overall, there was no significant difference in ARF between patients who received the drug (29%) and those who did not get an infusion (20%). Nor was there a big difference in mortality: 23% for those receiving nesiritide and 16% for those who did not get the drug.

In the nondrug group, lower glomerular filtration rate and older age were independent predictors of ARF. For the nesiritide group, hypertension and elevated blood urea nitrogen/serum creatinine were independent predictors. Mortality predictors in the nesiritide group included brain natriuretic peptide, intensive care admission, blood urea nitrogen/serum creatinine, and digoxin use.

However, 12 patients (23%) died after developing ARF, and 9 of those were taking nesiritide, suggesting an association. The researchers looked for some sort of link and found that among patients who died after developing ARF, the drug was an independent predictor of mortality when they used Cox analysis.

Dr. Iglesias and his colleagues concluded that patients who received nesiritide and who then developed ARF may be at increased risk of death.

In a larger, not-yet-completed investigation, he and his colleagues studied 1,412 heart failure patients, of whom 335 received nesiritide. Of the 1,412 patients, 186 (13%) developed ARF. Among those, 82 (44%) had received nesiritide, which was associated with a significant increase in the risk of ARF (odds ratio of 5.93). Patients who developed ARF also had significantly higher mortality: 18%, compared with 5% for those without ARF (odds ratio of 4).

The independent predictors for ARF were chronic renal failure, inotropic support, and nesiritide. Using a univariate analysis, the researchers found that the independent predictors for mortality included older age, digoxin use, nesiritide, inotropic support, chronic renal failure, and a history of hypertension.

Both Dr. Iglesias and a coauthor, Dr. Lance Berger, receive honoraria from Fremont, Calif.-based Scios Inc., which makes Natrecor.

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