Once-Promising Heart Failure Drug Fails in Trial
WEDNESDAY Oct. 6, 2010 -- A new experimental drug for treating patients who have acute heart failure plus kidney failure did not show any overall benefit, indicating that the future of this particular drug, called rolofylline, is over.
"I think this is the end of the story for this drug," said Dr. Barry Massie, lead author of a study appearing in the Oct. 7 issue of the New England Journal of Medicine. "There was a very promising pilot trial but these results . . . were neutral. I am disappointed," he said.
The results were presented last year at the European Society of Cardiology meeting. Shortly before that, drug company Merck, which has been developing the medicine and which funded this study, announced that it would not be filing for U.S. Food and Drug Administration approval for rolofylline.
Rolofylline is known as an A1-receptor antagonist and is intended to make diuretics work more effectively.
Other drugs in the same class of medications that were developed by other companies have met with similarly disappointing results after promising early results, said Massie, who is chief of the cardiology division at the San Francisco VA Medical Center and professor of medicine at the University of California, San Francisco.
He explained that kidney problems are a major complication of heart failure and "those patients who develop renal [kidney] failure in the course of treatment have a much higher hospital admission and death rate."
This may be at least partly because patients are taken off of certain cardiac medications in order to improve kidney function.
"This is sort of a perfect storm," Massie said.
For this study, just over 2,000 patients who had been hospitalized for acute heart failure and kidney problems were randomly assigned to receive a placebo or 30 milligrams of rolofylline daily intravenously. Treatment lasted for up to three days.
Rolofylline did not prolong survival or improve heart failure or kidney function when compared with the placebo.
And in contrast to the placebo group, some patients taking rolofylline had seizures, indicating that the drug was able to cross the blood-brain barrier. Seizures are a potential side effect for this class of drugs.
"[We] had hoped that the drug didn't cross the blood-brain barrier," Massie said.
One expert was similarly disappointed with the study results.
"Rolofylline certainly does not seem to have benefit in terms of risk of mortality (or death) and hospital readmission," noted Dr. Tara Narula, a cardiologist with Lenox Hill Hospital in New York City. "At this point, unfortunately, we're left with what we have in our arsenal, which we've [already] had for many years."
That includes IV loop diuretics, ACE inhibitors and beta blockers, she said.
There's more on heart failure at the American Heart Association.
Posted: October 2010