Study Supports Controversial Heart Failure Drug

Critics quickly put the pressure on the drug's maker, Scios Inc., to initiate a large, prospective randomized controlled trial. Such a trial is already in the recruitment phase and organizers hope to gather 7,000 patients.

The Stanford study -- also funded by Scios -- was much smaller and was conceived before the controversy broke, Witteles said.

In the trial, 75 patients admitted to a hospital with ADHF received either Natrecor or a placebo within 12 hours of admission, for two days.

Since impaired kidney function was the main area of concern, the Stanford researchers used standard methods to assess each patient's kidney function during the first seven days of hospitalization. They also looked at rates of patient death or rehospitalization, or the need for dialysis or other care, over the following 30 days.

"The main findings were that nesiritide did not cause renal [kidney] dysfunction in high-risk patents who were hospitalized with heart failure," Witteles said. He stressed, however, that Natrecor also failed to prevent kidney trouble, so doctors should not use the drug in hopes of preserving kidney function.

Average length of hospital stay was similar for those on Natrecor or placebo -- four days. Four patients taking Natrecor died within 30 days compared to two on a placebo, but those numbers were far too small to represent any solid trend, Witteles said.

So, why do the Stanford results differ from those of prior studies?

According to Witteles, the patients in his team's study more accurately reflect those seen by doctors generally -- older patients whose situation when they arrive at the hospital is not so dire that they need the highly concentrated shot of Natrecor used in earlier trials.

"The lower dose [we used] is not associated with renal dysfunction the way that perhaps the higher dose is," Witteles reasoned. The lower dose is also the one approved for use by the FDA, he added.

Witteles also believes that Natrecor has both beneficial and detrimental effects on the kidneys. At the lower dose used in the study, "they simply cancelled each other out," he said, leading to a nil effect on kidney function.

The bottom line, according to Witteles: "I think [Natrecor] should be used in a particular context as well as in a particular fashion. I still believe that nesiritide is a very useful drug in the appropriate person."

That explanation doesn't satisfy Sackner-Bernstein, however, who called the new study "well-designed and well-executed" but also flawed.