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Subject: EARLY TREATMENT CONFIRMED AS KEY TO STROKE RECOVERY


U.S. Department of Health and Human Services

NATIONAL INSTITUTES OF HEALTH

NIH News

National Institute of Neurological Disorders and Stroke
http://www.ninds.nih.gov/

EMBARGOED FOR RELEASE
Thursday, March 4, 2004
6:30 p.m. ET

Contact:
Marian Emr or Margo Warren
301-496-5924


EARLY TREATMENT CONFIRMED AS KEY TO STROKE RECOVERY

A study in the March 6, 2004, issue of "The Lancet"*
confirms the benefits of getting stroke patients to the hospital quickly
for rapid thrombolytic treatment. The study provides the results of an
extensive analysis of more than 2,700 stroke patients in six controlled
clinical trials who were randomized for treatment with thrombolytic t-PA
or a placebo

While physicians have known since a breakthrough study in
1995 that early treatment with thrombolytics can improve a stroke
patient's chance of a full recovery, only an estimated 2 to 5 percent of
all eligible acute stroke patients in the U.S. are being treated with
thrombolytics.

Stroke patients who were treated within 90 minutes of the
onset of their symptoms showed the most improvement. The
study suggests that t-PA given up to 4 hours after the
onset of symptoms may be of benefit, but the authors
caution that as time goes on there is a diminishing effect
of treatment, and there is estimated to be almost no
benefit when treatment is at 6 hours.

"Once again we learn that time is brain," said John R.
Marler, M.D., one of the study authors and associate
director for clinical trials at the National Institute of Neurological
Disorders and Stroke (NINDS), a part of the National Institutes of
Health (NIH). "Although rapid stroke treatment presents a great
challenge to physicians and may require substantial change in many
health care systems, we now have stronger evidence that rapid early
treatment offers the best chance of recovery for acute ischemic stroke
patients."

Thrombolytics work as "clot busters," breaking up the clot
that appears in the brain during an ischemic stroke, and allowing blood
to flow freely again in the occluded or blocked artery. Patients must
have computerized tomography
(CT) scans of the brain taken before treatment begins to confirm that
the stroke is caused by a clot. Seventy-five percent of patients who
were treated within 60 minutes of stroke onset had the best chance of
having a complete or partial reopening of the occluded artery.

Another significant finding reported by the authors is that severe
stroke patients tend to present to the hospital earlier than patients
with milder strokes, and those who were treated had much better
recoveries than patients who were given a placebo. This means that the
greatest effect of early treatment was seen in the group with the most
to gain in terms of reducing long-term disability.

"This study confirms that door-to-needle time is just as critical in
stroke as it is in heart attack. We need to work on breaking down the
current barriers to rapid stroke treatment," said Story C. Landis,
Ph.D., NINDS director.

The pooled data from the trials -- two of which were
sponsored by pharmaceutical companies and one that was by
the NIH -- represent the work of 16 teams of researchers
and several statisticians around the world. "This
scientific work is a good example of a cooperative effort between the
Federal Government and the pharmaceutical industry," said NIH Director
Elias A. Zerhouni, M.D. "By sharing these important data, the scientists
have advanced our understanding of stroke treatment, which we hope will
lead to significant improvements in treating this major disease."

In 1995, the NINDS t-PA Study Group published the results
of two randomized clinical trials with more than 600
patients that showed a clear benefit of t-PA in stroke
patients treated within 3 hours of onset and a diminishing effect for
patients treated later than that. [The U.S. Food and Drug Administration
(FDA) approved t-PA as a treatment for acute stroke in June of 1996,
with the restriction that treatment begin within 3 hours of the stroke
onset.]

Two other groups have conducted large randomized trials of
t-PA for stroke, using longer windows of treatment. The European
Cooperative Acute Stroke Study (ECASS) conducted two trials using a
6-hour window and the Alteplase ThromboLysis for Acute Noninterventional
Therapy in Ischemic Stroke (ATLANTIS) investigators conducted two trials
with treatment windows of 5 and 6 hours each. The investigators from the
three studies collaborated to test the hypothesis that pooling their
patient data would show the importance of time to treatment, and their
results appear in "The Lancet".

To measure favorable outcome at 3 months, investigators
used various neurological scales to measure post-stroke disability. They
also looked at the occurrence of hemorrhage, the primary risk of t-PA
use. The final analysis included 2,775 patients treated at 300 hospitals
from 18 countries. The median age was 68 years and the median time of
"onset to treatment" was 243 minutes. Substantial intracerebral
hemorrhage occurred in 5.9% of the treated patients as compared to 1.1%
of placebo patients.

Although the data in "The Lancet" paper suggest that the beneficial
effect of t-PA may extend beyond 3 hours (from 181 to 270 minutes), the
authors caution that large prospective randomized trials would be
required to confirm this finding and that this does not justify any
delays in treatment. The ATLANTIS trial enrolled 79% of patients in the
4-5 hour window and failed to demonstrate efficacy.

"The most appropriate interval for beginning thrombolytic treatment
remains to be clarified," the authors write in "The Lancet"; however
they urge those in the health care system, from paramedics to
physicians, to set a target of 1 hour after arrival in the emergency
room to begin intravenous thrombolytic treatment for patients with acute
ischemic stroke.

The ATLANTIS trial was funded by Genentech, Inc., the
makers of t-PA. The ECASS trial was funded by Boehringer Ingelheim
Pharmaceuticals, which markets t-PA in Europe. The NINDS trials were
funded by the NIH. Genentech provided the study drug and additional
study monitoring as required by the FDA.

The NINDS is a component of the National Institutes of
Health within the Department of Health and Human Services
and is the nation's primary supporter of biomedical
research on the brain and nervous system.

This release will be posted on EurekAlert! at http://www.eurekalert.org
and on the NINDS website at
http://www.ninds.nih.gov/news_and_events/index.htm.

--------------------------------------

*"Association of outcome with early stroke treatment:
pooled analysis of ATLANTIS, ECASS, and NINDS
rt-PA stroke trials." Authors: The ATLANTIS, ECASS and
NINDS r-t-PA Study Group Investigators. "The Lancet", March
6, 2004, Vol. 363, pp. 768-774.

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