A giant new study out today shows that a controversial Johnson & Johnson heart failure drug doesn't kill people or cause serious kidney problems, as previous studies have suggested. But the study showed that the drug doesn't seem to do all that much to help improve symptoms of acute heart failure, either.
The results should provide an end to the long and strange story of the J&J drug Natrecor. It rose to fame after it was approved based on a small study showing it appeared to help symptoms of patients reporting to the hospital with acute heart failure symptoms. Sales rose meteorically after some doctors started using it also in outpatient clinics in non-hospitalized patients. This was very profitable for both the doctors and for Johnson & Johnson.
But then sales dropped just as quickly after studies combined together the results of previous studies and showed that Natecor seemed to boost the risk of death. This led to a huge controversy over the widespread unproven "off-label" use in these outpatients.
The new 7000 patient showed the drug did not kill people, nor did it help very much in preventing symptoms either, when compared to patients that were treated aggressively with standard therapy. The modest symptom improvement was not statistically significant. "The drug does not have a long-term effect on clinical outcomes one way or another," says Robert Califf of Duke University, who presented the big new study of 7000 patients at a news conference here at a meeting of the American Heart Association in Chicago.
The earlier study in 2005 showing a death risk "was wrong in its conclusion" that the drug killed people, admitted University of Michigan's Keith Aaronson, who was involved in the earlier work showing a risk. This was not due to a technical flaw in the previous study, but just because the data available at the time was not rigorous enough to reach a definitive conclusion.
Both the apparent miraculous benefits attributed to the drug and the apparent harm turn out both to have been a mirage, the product of the inadequate trials that were done before the drug was approved. The story of Natrecor highlights the enormous impact of the placebo effect, the power the expectation improvement to influence patient's subjective assessment of symptoms.
Many acute heart failure patients' symptoms get better rapidly anyway with standard care. If you give fancy new drugs, doctors may wrongly attribute the improvement to the new drug. "The issue here is the placebo effect," says Califf. Heart patients who get standard treatment get better quickly, so it is hard to tell without doing a rigorous trial whether it was due to the new treatment or now. "The only way to sort that out is to do a controlled trial that sets apart the treatment of interest from all the other things that are happening."
"We constantly put drugs on the market without doing the right outcomes trial. If this trial had been done early, the clinician would have better idea of the potential limited role for this treatment, but they already would have known it is not harmful either," says Califf.
Kentucky cardiologist Melissa Walton-Shirley says years ago she administered Natrecor to small number of heart patients outside of the hospital. (She didn't profit off of it, unlike some big clinics specializing in outpatient Natrecor use.) The patients seemed to do much better. But now she agrees that the apparent benefit was probably a placebo effect. The real reason the patients may be she was monitoring them more carefully, and adjusting their drug. Because of the extra attention, the patients may have been checking their weight more carefully and otherwise doing a better job at caring for themselves.
One question that remains is does the Natrecor drug still have a role in heart failure patients, and if so, which patients should get it? The good news for Johnson & Johnson is that the big new study should end concerns that its drug is not safe. It could allow future researchers to do more detailed studies of what groups of patients can be helped by the drug, said Alfred Bove, former president of the American College of Cardiology. "It is leaving us with the idea that we have to find the subsets of patients who will benefit," he said.Source: Robert, Langreth, Forbes.com
Author: Jeffery Kluger, Time Magazine
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