"When the FDA approved nesiritide, they acknowledged that it could be associated with a 50 percent increased risk of death," he adds. "But it seems the FDA believed that physicians could judge how to balance the risks and benefits for individual patients. Our meta-analysis demonstrates that the risk may be even higher. In view of the relatively modest symptomatic benefit this drug provides, a death risk of this size should take precedence in a physician's treatment decision."

With that in mind, he says, the first choice for treatment should be diuretics, which aren't perfect but which are effective and cost pennies in comparison with hundreds of dollars for nesiritide. And he questions the intermittent outpatient use of nesiritide, which is covered by Medicare in several states. That approach infuses patients with the drug up to three times a week, to ease ongoing non-acute symptoms.

"Although the outpatient use of nesiritide is now being explored in a Scios-funded trial, we're concerned the study will not be large enough to allow for risks to be seen if they are present," says Aaronson.

In addition, nesiritide is currently being used in patients who have had open-heart surgery, but this too is likely to be a misguided approach, the authors say. "Very few patients require a vasodilator after open-heart surgery, but kidney dysfunction is a major concern post-operatively," Sackner-Bernstein says. "In addition to this mortality risk in patients with acutely decompensated heart failure, the meta-analysis we reported last month contradicted the perception that nesiritide protects the kidneys. Between these two analyses, and in the absence of a randomized controlled clinical trial, it's hard to see any rationale for the use of nesiritide in patients post-operatively."

The new analysis used data from the NSGET, VMAC and PROACTION trials. Nine other studies were not included because th
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Contact: Kara Gavin or Sally Pobojewski
kegavin@umich.edu
734-764-2220
University of Michigan Health System
19-Apr-2005