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Emergency Treatment for Stroke
U.S. Department of Health and Human Services
National Institutes of Health
For Immediate Release: December 14, 1995
A five-year clinical trial has shown that treatment with the
clot-dissolving drug t-PA is an effective emergency treatment for acute ischemic
stroke despite some risk from bleeding. The trial found that carefully selected stroke
patients who received t-PA treatment within 3 hours of their initial stroke symptoms were
at least 30 percent more likely than untreated patients to recover from their stroke with
little or no disability after three months. The nationwide study of more than 600 stroke
patients was organized and funded by the National Institute of Neurological Disorders and
Stroke (NINDS). Results appear in the December 14, 1995, issue of The New England
Journal of Medicine.
"Stroke, which leaves millions of adults disabled, is one of the most devastating
and costly health problems that we face," said Zach W. Hall, Ph.D., director of the
NINDS. "The positive result of this trial should be encouraging to all Americans at
risk of stroke who hope to live to a healthy, independent old age. A notable feature of
this study is that its quality sets a very high standard for future clinical trials."
Each year, about 500,000 Americans suffer a stroke. Of these strokes, 400,000 are
ischemic, caused by a blood clot that reduces blood flow to the brain. The remaining 20
percent are hemorrhagic strokes, caused by bleeding into the brain. Stroke ranks as the
third leading cause of death in the country after heart disease and cancer, killing about
150,000 Americans each year. The overall cost of stroke to the nation is estimated to be
$30 billion each year.
In the two-part NINDS trial conducted at nine centers across the country, 624 patients
received either intravenous t-PA or a placebo within 3 hours of the initial symptoms of a
stroke. Before treatment could start, a medical team performed a CT scan to be sure the
stroke was not caused by bleeding, administered a variety of blood tests, and obtained
informed consent. Part 1 of the trial was designed to look for marked improvement in the
patients' conditions 24 hours after treatment and, secondarily, to examine efficacy of the
treatment at 3 months. Part 2 was designed to confirm the long-term benefit of the drug.
In both parts, there was a dramatic 3-month improvement in those who received t-PA. The
investigators demonstrated that the number of patients with complete or almost complete
recovery was increased by 30 percent or more as measured by four different medical outcome
scales. For every 100 patients receiving t-PA, at least 11 more had an excellent recovery
as measured by the four scales. A powerful statistical approach, the global test
statistic, combined information from all four outcome scales in order to compare the odds
of an excellent outcome between treatments. The overall odds in favor of the t-PA treated
group were 1.7 times greater than the placebo group.
The drug t-PA works by dissolving the blood clots that block brain arteries and cause
over 80 percent of all strokes. Although it has been proven effective in the treatment of
heart attack, t-PA's potential as a treatment for stroke has been unclear because of an
increased risk of brain hemorrhage. In the NINDS trial, bleeding into the brain within 36
hours of treatment worsened strokes in 6.4 percent of those patients who received t-PA
compared to 0.6 percent of those who received placebo. Overall, however, there were
greater numbers of stroke survivors who were able to live normal lives in the t-PA treated
group, leading the investigators to conclude that the use of t-PA for stroke is
beneficial. Furthermore, the NINDS trial showed lower levels of brain hemorrhage than
previously published stroke trials involving clot-dissolving drugs.
According to the investigators, timing is a critical factor. Over the past 12 years
basic and clinical scientists have been working to discover the window of opportunity for
emergency treatment of stroke. Based on research in animal models and clinical
observations, the NINDS t-PA clinical investigators designed their highly coordinated
emergency treatment program to work within the narrow time window of 3 hours.
"One of the keys to the success of this study was treating stroke as the true
emergency that it is. The concept that stroke is every bit as serious as heart attack is
one that physicians must recognize in order for this new treatment to have widespread
benefit," said Thomas Brott, M.D., clinical investigator at the University of
Cincinnati Medical Center in Ohio, the study site that treated the most patients.
Because of the risks involved, investigators urge physicians to take a cautious
approach before introducing the use of this new stroke treatment. "It would be a
mistake for physicians with limited experience in treating stroke to rush in and begin
treatment with t-PA," said Patrick D. Lyden, M.D., clinical investigator at the
University of California at San Diego School of Medicine. "Starting t-PA treatment
more than three hours after stroke could easily result in a much higher rate of bleeding
into the brain." He also emphasized that t-PA should be given only after a complete
evaluation of the patient including a careful examination of a brain CT scan
The investigators agree that substantial efforts by the health care community will be
necessary before t-PA can be used on a widespread basis. These efforts include intensive
public education about the signs of stroke and the importance of immediate treatment; the
organization and training of medical personnel to evaluate and treat stroke patients; as
well as planning for the rapid transport of patients to treatment centers through
emergency medical services.
"This is a major breakthrough that will forever change the way stroke is treated.
After years of discouraging results, the positive results of this trial will lead to
renewed efforts to make even more progress in treating and preventing the devastating
consequences of stroke," said John R. Marler, M.D., NINDS neurologist and project
officer for the trial.
Principal investigators participating in the trial were: Thomas Brott, M.D.,
University of Cincinnati Medical Center, OH; Patrick D. Lyden, M.D., University of
California, San Diego; James C. Grotta, M.D., University of Texas Medical Center,
Houston; Thomas Kwiatkowski, M.D., Long Island Jewish Medical Center, New Hyde
Park, NY; Steven R. Levine, M.D., Henry Ford Hospital, Detroit, MI; Michael R.
Frankel, M.D., Emory University, Atlanta, GA; E. Clarke Haley, Jr., M.D.,
University of Virginia Medical Center, Charlottesville; Michael Meyer, M.D.,
University of Tennessee Medical Center, Knoxville and Memphis. Barbara C. Tilley, Ph.D.,
headed the Coordinating Center at Henry Ford Health Science Center, Detroit, MI. K.M.A.
Welch, M.D., Henry Ford Health Science Center, Detroit, MI, was the medical monitor
and chairman of the steering committee. John R. Marler, M.D., was the NINDS project
officer for the trial.
The NINDS is the nation's principal supporter of research on the brain and nervous
system and a lead agency for the Congressionally designed Decade of the Brain. The
Institute supports and conducts a broad program of basic and clinical neurological
investigations and is part of the National Institutes of Health, located in Bethesda, MD.
t-PA= tissue plasminogen activator.
The National Institute of Neurological Disorders and Stroke t-PA Stroke
Study Group. "Tissue Plasminogen Activator for Acute Ischemic Stroke." The
New England Journal of Medicine, Vol. 333, No. 24, pp. 1581-1587.
For more information: NINDS
Office of Scientific and Health Reports, 301-496-5751
Last Updated: March 22, 1999.
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892
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