Major new study shows Natrecor is safe, but not very effective
A major new clinical trial of more than 7,000 patients with severe congestive heart failure has dismissed concerns that the drug Natrecor is linked to an increased risk of kidney failure and death, researchers said Sunday. Unfortunately, the study also found that the intravenous drug provides very little benefit.
An estimated 6 million Americans suffer from congestive heart failure, in which the heart cannot pump blood effectively throughout the body. Symptoms include, aong a variety of other problems, shortness of breath.
Natrecor, known generically as nesiritide, was first marketed in the U.S. in 2001 for improving shortness of breath (dyspnea) in patients hospitalized with acute heart failure. Sales quickly climbed to $230 million per year. In 2005, however, two meta-analyses involving more than 1,000 patients suggested that the drug carried unwarranted risks and sales fell to about $100 million per year.
“Clinicians were initially told that nesiritide had a major effect on dyspnea, so it was widely used soon after it came on the market,” said Dr. Robert M. Califf of the Duke University School of Medicine. “Then meta-analyses indicated that nesiritide might increase mortality and cause renal dysfunction, so its use declined dramatically. We now know that neither view that drove clinical practice was correct; the drug is safe, but provides only a modest benefit for dyspnea.”
The drug was also being used off-label by some physicians to treat patients with milder heart failure who were not hospitalized. In February 2009, the U.S. Justice Dept. joined two civil lawsuits charging Johnson & Johnson -- which had purchased the drug’s original manufacturer, Scios, Inc. --with aggressively promoting the off-label uses. Those suits have not yet been settled.
In 2006, Scios asked Dr. Eugene Braunwald, a cardiologist at Harvard University Medical School, to head an independent advisory committee to study the drug. The committee recommended two trials, Braunwald said Sunday at a Chicago meeting of the American Heart Assn. One trial, headed by Dr. Clyde Yancy of the Baylor University Medical Center, studied the use of the drug in 980 patients with mild heart failure. There was no evidence of improved survival or decreased hospitalization and the researchers concluded that “nesiritide should not be given as an intermittent outpatient infusion.”
Califf and Dr. Adrian Hernandez of Duke reported results from the second study at the meeting. They and their colleagues studied 7,143 patients with acute decompensated heart failure who were randomly assigned to receive either nesiritide or placebo for 24 to 168 hours in addition to standard medical care. The study included 398 sites in North America, Europe, Latin America and Asia Pacific.
The researchers found that six hours after treatment, 15% of nesiritide patients had significant improvements in breathing, compared to 13.4% of those receiving placebo. At 24 hours, the corresponding figures were 30.4% and 27.5%. At the end of 30 days, the mortality rate for those receiving nesiritide was 3.6% compared to 4% for those receiving placebo.
“The good news for neseritide from the ... trial is that it does not support the concerns. There is no evidence that it is associated with an increased risk of mortality,” Braunwald said at a news conference. “The less good news is that the trial provides very little evidence that a physician would improve the outcome of a patient who is receiving good standard care [by using it]. The economic effects are self-evident.”
