BOCA RATON, FLA. — The brain natriuretic peptide, nesiritide, which is used to treat acute heart failure symptoms, did not facilitate diuresis or protect renal function in a small study of stable hospitalized patients.
Many clinicians believe nesiritide (Natrecor, Scios Inc.) facilitates furosemide diuresis and prevents renal dysfunction, Margaret M. Redfield, M.D., said in an interview. However, a recent metaanalysis indicated that the agent might actually increase the risk of renal dysfunction (Circulation 2005;111:1487–91).
To sort it out, Dr. Redfield and her associates studied 65 patients who were hospitalized for decompensated heart failure and who were treated with a standard dose of nesiritide for relief of their heart failure symptoms. They were randomized to nesiritide as a 2-mcg/kg bolus at admission and a 0.01-mcg/kg per minute infusion at 48 hours (34 patients) or to standard therapy (31 patients).
The participants also received 40-mg b.i.d. intravenous furosemide if they had mild renal dysfunction at baseline, defined as a creatinine clearance of 40–60 mL/min. They received 80-mg b.i.d. intravenous furosemide if they had moderate renal dysfunction, or a creatinine clearance of 20–39 mL/min.
“We looked at nesiritide in the broader heart failure population where you don't need an acute effect,” said Dr. Redfield, professor of medicine, Mayo Clinic College of Medicine, Rochester, Minn.
Approximately one-quarter of heart failure patients experience renal dysfunction during hospitalization, and the researchers sought to determine if nesiritide is protective, Dr. Redfield said during a poster session at the annual meeting of the Heart Failure Society of America.
A secondary objective was to determine if the agent could obviate the need for furosemide diuresis in some patients.
Mean baseline creatinine was 1.8 mg/dL in the nesiritide group and 1.7 mg/dL in the standard therapy group; by 48 hours, the mean changes were increases of 0.12 mg/dL and 0.07 mg/dL, respectively. Mean baseline brain natriuretic peptide level was 640 pg/mL for the nesiritide group and 538 pg/mL for the standard therapy group; by 48 hours, the mean changes were a 474 pg/mL increase in the nesiritide group and a 59 pg/mL decrease in the control group. Total furosemide use was 272 mg in the nesiritide group and 255 mg in the standard treatment group at 48 hours.
“Nesiritide causes no harm, but has no significant benefit,” Dr. Redfield said. “Nesiritide did not enhance the response to furosemide. We hypothesized that nesiritide should have a beneficial effect on renal function—we didn't see that either.”
Systolic blood pressure was lower in the nesiritide group at 24 hours, but not significantly different between groups by 48 hours.
“The standard dose was designed for hemodynamic effects,” Dr. Redfield commented. “The next step is to look at a lower dose, which might provide renal protection.”