Scios and FDA notified HealthCare Professionals of revisions to the Adverse Reactions / Effect on Mortality section of the prescribing information for Natrecor ( Nesiritide ).
There have been several published reports about Nesiritide, a treatment for patients with acutely decompensated congestive heart failure ( ADHF ) with dyspnea.
These reports raise the question of whether Nesiritide may have adverse effects on survival and kidney function compared to control agents ( generally Nitroglycerin and diuretics ).
Nesiritide is an effective drug with a well-described safety profile for patients requiring intravenous treatment for acutely decompensated congestive heart failure with dyspnea at rest or with minimal activity.
Heart failure affects about 5 million Americans, and ADHF is a life-threatening condition for which there are limited treatment options. Advanced ADHF patients have a 30% risk of mortality within one year.
Nesiritide was approved for the treatment of advanced ADHF on the basis of its ability to improve dyspnea and reduce pulmonary capillary wedge pressure. In these studies the mortality was somewhat greater in the Nesiritide group than in the comparator groups and this has been noted in labeling since Natrecor was first marketed.
It was not clear that the small increase was drug related.
Updated labeling for Natrecor was approved recently based on ongoing discussions with the U.S. Food and Drug Administration.
The revised label language is based on the analyses of survival data from seven controlled studies, including the three studies used in the meta-analysis that recently appeared in JAMA.
The label now includes 30-day mortality data in addition to the 180-day data that previously appeared in label.
The analyses show a nominal increase in mortality, but the increases are not statistically significant, and thus remain of uncertain clinical significance.
In seven clinical trials ( 1700 patients ), the 30-day mortality rate is 5.3% in the Nesiritide treatment group as compared with 4.3% in the group treated with other standard medications.
In four out of these seven clinical trials where it was measured, the 180-day mortality rate is 21.7% in the Nesiritide treatment group as compared with 21.5% in the group treated with other standard medications. None of these mortality differences reached statistical significance. As described in the revised labeling, There were few deaths in these studies, so the confidence limits around the hazard ratios for mortality are wide.
The studies are also small, so some potentially important baseline imbalances exist among the treatment groups, the effects of which cannot be ascertained.
Recent news focused on a meta-analysis published in JAMA regarding the potential risk of mortality associated with the use of Natrecor.
The same author published another meta-analysis that focused on the renal effects of Natrecor in the March 29 th issue of Circulation.
The JAMA meta-analysis is a three-study subset of the original clinical research on Natrecor.
The authors state that this meta-analysis is hypothesis generating only, and the observed differences were not statistically significant.
Eugene Braunwald, distinguished Hersey Professor of Medicine, Harvard Medical School, and Chairman of TIMI Study Group at Brigham and Womens Hospital in Boston, has agreed to convene a panel of external experts to review all available studies.
Source: Scios, 2005