STROKE DRUG INEFFECTIVE, ADDS TO RISK, STUDY FINDS

A type of drug physicians have depended on for decades to treat stroke
victims has more risks than benefits, says a nationwide study published
today in the Journal of the American Medical Association.

The anti-coagulant drug, which is closely related to heparin, has been used
by neurologists since the 1960s. But heparin was never the subject of a
well-designed study to determine its effectiveness, Dr. Paul Akins, acute
stroke co-director for Mercy Healthcare of Sacramento and an investigator
in the study, said Tuesday.

"It's been very common to use heparin to treat stroke patients, without
very good evidence to support its use, and patients were harmed by it; some
bled into their stroke and it killed them," Akins said.

Ischemic stroke occurs when a blood clot blocks an artery and deprives the
brain of blood flow and oxygen, thus damaging part of the brain.

For a subset of patients, the 10 percent to 20 percent whose blockage is in
the carotid artery -- the large artery in the front of the neck -- the
drug, seemed potentially beneficial, Akins said. "But overall, patients did
not benefit and there were bleeding problems (in the brain) related to it.

"This study says you have to think twice about starting stroke patients on
low molecular weight heparinoid and heparin, and that doctors need to
rethink whether this drug should be used," Akins said.

Each year, 750,000 people in the United States are the victims of stroke.
It is the No. 1 cause of disability in adults, the No. 1 cause of people
being transferred from hospitals to nursing homes, and this country's No. 3
killer.

The study, sponsored by the National Institute of Neurological Disorders
and Stroke, focused on the drug ORG 10172, which is scientifically known as
danaparoid sodium, a close relative of heparin. The study was conducted at
36 centers across the United States between 1990 and 1997 and included
1,282 patients with mild to moderate strokes.

The goal was to determine how patients fared long-term after receiving the
intravenously-administered compound within 24 hours of their stroke and
then continuously for a week. About 75 percent of the patients did well
after three months, whether they were in the group receiving the drug or in
the placebo group. The difference was insignificant.

"So there is no sustained benefit to this treatment," said Akins. He added
that so far only two treatments for stroke have clearly proven beneficial.
One is TPA, approved two years ago by the FDA, which can dissolve the clot
blocking the artery. But it must be given within three to six hours of the
stroke.

The other is aspirin. "Two giant studies show a tiny benefit if aspirin is
given within the first few days," Akins said.

Researchers were disappointed by the results of the study, said Dr.
Birgitte Bendixen, principal investigator at the University of Iowa medical
school and assistant professor in the division of cerebral vascular
disease.

They had hoped the heparin-like drug would produce less bleeding and could
be proven beneficial if given with 24 hours, but that was not the case, she
said.

"We still found bleeding a problem," she said. "And the trial showed that,
overall, the stroke in progression was not affected at all." Further, there
was no benefit in preventing a recurrent clot from the heart, because that
risk was found to be very low.

"What we have is a drug with a clear risk and no clear benefit except in
people with high degree of narrowing of the carotid artery, which was about
10 percent of people in the study," said Bendixen.

"For a significant contingent of stroke doctors or neurologists who placed
a lot of trust in heparin as the drug to grab when unsure, or when things
are getting worse, this is a very significant finding. I think it will
change a lot of people's behavior," she said.

That patients in the placebo group did as well is a testament to
rehabilitation therapy, Bendixen said. Also, she added, the study results
may have been skewed by the fact that half the patients had suffered only
mild strokes, which typically have better outcomes.

The study is significant in that it answered the question of whether ORG
10172 is safer and better, and that clearly is not the case, said Dr. David
Dozier Jr., director of Sutter Hospitals Neuroscience Institute.

However, he noted, "heparin has been increasingly eclipsed by other forms
of blood thinners, and our recognition of who should get it has narrowed to
a smaller base. Heparin hasn't been the cornerstone of therapy, only one
weapon in the armament in treating patients with strokes that got worse
after treatment in the hospital."

Dr. Fletcher McDowell, professor of neurology at Cornell University and
vice chairman of the National Stroke Association, agreed the study helped
clarify the best course of treatment for stroke victims.

"The most important thing in successfully treating people with stroke is to
get them treatment as quickly as possible to reduce brain damage and
disability," he said.

Copyright ) 1998 The Sacramento Bee