Anti-Clotting Drug Trial Shortened by Bleeding Problems
THURSDAY Jan. 24, 2008 -- A study of the new anti-clotting drug idraparinux for preventing strokes was stopped early because of excess bleeding, a problem that has plagued the medication.
But the researchers said the trial could open the way to at least limited use of the drug.
The bleeding problem seems to occur primarily in two groups of people -- those over 70 and those with kidney impairment, said study lead author Dr. Harry R. Buller, chairman of the department of vascular medicine at the Academic Medical Center in Amsterdam, the Netherlands.
"We have started a new study in which we have adapted the dose for persons with renal [kidney] impairment," Buller said. "This is another chance to show that this concept is alive."
Idraparinux is one of a number of anti-clotting agents being tested as possible replacements for the current standby warfarin (Coumadin), which is highly effective but difficult to manage, requiring frequent blood tests.
Buller is an idraparinux enthusiast. "Its beauty is twofold," he said. "It uses the body's natural defenses, and it can be given once a week. But much to our regret, particularly in persons over 70 or with some kind of renal impairment, the concentration of the drug builds up, and there is excessive bleeding."
The new study was stopped after enrollment of 4,576 people with atrial fibrillation -- an irregular heartbeat -- after excess bleeding occurred in 19.7 percent of those given weekly injections of idraparinux, compared to 11.3 percent of those taking other anti-clotting agents.
The findings were published in the Jan. 26 issue of The Lancet.
To outside observers, that was a depressing repeat of studies, reported last September, that showed the drug to be effective against deep vein thrombosis and long-term prevention of blood clots but with a high rate of serious bleeding complications.
"This is clearly a setback," said Dr. Alan Go, associate director for clinical research at Kaiser Permanente of Northern California, co-author of an accompanying editorial in the journal.
Go, like other experts in the field, acknowledged that "we are eager to find a replacement for warfarin. It is a remarkably effective drug but challenging to deliver and challenging to take."
Buller said that if all turns out as well as he hopes, idraparinux could be a useful alternative for many people who could get the needed anti-clotting activity with a single weekly injection, while forgoing the constant blood tests required for warfarin users.
"That might lead to some effective agent," Go said. "It's certainly possible, and I wouldn't rule it out. But we would need another large trial to prove it."
Idraparinux is not the only anti-clotting medication in the race to supplant warfarin, Go noted. "At least two oral inhibitors are being tested," he said. "There are different approaches to affecting clotting factors, and there is a very aggressive drive to find something to replace warfarin."
Buller said: "The primary question is, can this drug replace warfarin in preventing stroke? The answer, I think, is yes, but not in subgroups of individuals."
You can learn about the role of anti-clotting drugs in preventing strokes from the Heart Rhythm Society.
Posted: January 2008