|Aspirin is Safer than Warfarin and
Just as Effective for Treating Blocked Arteries in
To reduce the risk of stroke, partial blockage of arteries
in the brain (intracranial stenosis) has for decades
been treated with drugs such as aspirin and warfarin
that reduce blood clotting. However, doctors have never
had good evidence for choosing one therapy over the
other. Now, results of a double-blind, randomized clinical
trial show for the first time that aspirin works as
well as warfarin with fewer side effects. The study
was funded by the National Institute of Neurological
Disorders and Stroke (NINDS), part of the National Institutes
of Health (NIH).
"This trial is good news. A simple low-cost drug works
just as well as one that requires complicated and expensive
monitoring and dose adjustments," says John R. Marler,
M.D., the Associate Director for Clinical Trials at
NINDS. The study appears in the March 31, 2005, issue
of the New England Journal of Medicine.*
Intracranial stenosis is caused by atherosclerosis
— fatty deposits that build up on the inner walls of
the arteries and restrict blood flow. Intracranial stenosis
causes about 10 percent of the 900,000 strokes and transient
ischemic attacks (TIAs) in the United States each year.
TIAs are transient strokes that last only a few minutes
and occur when the blood supply to part of the brain
is briefly interrupted. People with a stroke or TIA
due to intracranial stenosis have a greatly increased
risk of a second stroke — as much as 15 percent
per year. Studies in the 1950s suggested that anticoagulants
(a class of drugs that reduce blood clotting), such
as warfarin, can reduce the risk of stroke in people
with this disease.
In the new study, called the Warfarin Aspirin Symptomatic
Intracranial Disease (WASID) trial, investigators at
59 medical centers across the United States, led by
Marc I. Chimowitz, M.D., of Emory University in Atlanta,
compared warfarin to 1300 milligrams (mg) per day of
aspirin in a total of 569 patients for an average of
1.8 years. All of the patients had a greater than 50
percent blockage of a major intracranial artery and
had experienced a TIA or non-disabling stroke within
the 90 days prior to their enrollment in the study.
The investigators found that about 22 percent of the
patients had a subsequent ischemic stroke (caused by
blockage of an artery), brain hemorrhage, or death from
other blood vessel-related causes, regardless of whether
they received aspirin or warfarin. However, the rates
of major hemorrhage and death from all causes were significantly
higher in the patients treated with warfarin (event
rates for aspirin compared to warfarin, respectively,
were 3.2 percent vs. 8.3 percent for major hemorrhage
and 4.3 percent vs. 9.7 percent for death). Enrollment
in the study was terminated earlier than originally
planned on the recommendation of an independent Data
and Safety Monitoring Board because of concern for the
safety of the patients given warfarin.
Since warfarin treatment is a more expensive and complicated
therapy than aspirin, not using warfarin and preventing
the bleeding complications associated with it would
save more than $20 million per year in the United States,
Dr. Chimowitz estimates.
"The results of this study are only relevant to people
with intracranial stenosis," Dr. Chimowitz notes. People
who are receiving warfarin for other conditions, such
as an irregular heart rhythm (called atrial fibrillation)
or clots in the legs or lung, should not stop taking
the drug, as studies have found that it is the best
option in those conditions, he cautions.
The dose of aspirin used in this study — 1300 mg — is
much higher than the daily doses typically prescribed,
which range from 81 to 325 mg. While there is some concern
that doses of 1300 mg aspirin may increase the risk
of gastrointestinal bleeding, the investigators chose
this dose because it was the only amount for which earlier
studies had provided good preliminary data. "This is
the only dose we know is as effective as warfarin for
this disease, since it was the only dose studied. We
just don't know how other doses of aspirin would stack
up," says Dr. Chimowitz. The major bleeding risk on
high dose aspirin in WASID was similar to the major
bleeding risk in other stroke trials that have evaluated
lower doses of aspirin (e.g. 325 mg per day), he adds.
Most experts believe there are no advantages to aspirin
doses greater than 325 mg for stroke prevention, and
the U.S. Food and Drug Administration-approved dose
of aspirin for prevention of vascular events is 50-325
mg. Patients should consult their physicians before
beginning any long-term or high-dose aspirin treatment
Even with treatment, the rates of ischemic stroke in
this clinical trial were substantially higher than in
stroke prevention trials that have evaluated aspirin
and warfarin in patients with other causes of stroke.
This underscores that patients with intracranial stenosis
are at particularly high risk for stroke and that better
therapies are needed, the investigators note.
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.
* Chimowitz MI, Lynn MJ, Howlett-Smith
H, Stern BJ, Hertzberg VS, Frankel MR, Levine SR, Chaturvedi
S, Kasner SE, Benesch CG, Sila CA, Jovin TG, Romano
JG, for the Warfarin Aspirin Symptomatic Intracranial
Disease (WASID) Investigators. "Comparison of warfarin
and aspirin for symptomatic intracranial arterial stenosis." New
England Journal of Medicine, March 31, 2005, Vol.
352., No. 12, pp. 1305-1316.