A major study of African-American stroke patients was halted early when aspirin was found to be just as effective as the prescription antiplatelet drug ticlopidine in preventing recurrent stroke, heart attack and vascular death.
African-Americans are at approximately twice the risk of having a stroke compared to other racial groups, yet are often underrepresented in clinical trials. For this reason, medical researchers formed the African-American Antiplatelet Stroke Prevention Study (AAASPS), headquartered at Rush-Presbyterian-St. Luke’s Medical Center in Chicago. The AAASPS program involved 1,809 African-American patients at more than 60 hospitals and medical centers in the United States.
The study was designed to determine the efficacy and safety of aspirin and ticlopidine in preventing recurrent stroke and other vascular events in African-American patients who had already experienced a noncardioembolic ischemic stroke. Of the 1,809 patients, 902 randomly received 500 milligrams (mg) per day of ticlopidine, while 907 patients received 650 mg per day of aspirin. The study was double-blind, in that neither the researchers nor the participants knew which medication they were taking.
Although the study was scheduled to run until October 2003, it was halted in July 2002 by the data and safety monitoring board appointed by the National Institutes of Health when statistical analyses showed that there was less than a 1% chance of ticlopidine being significantly better than aspirin if the study were to continue to completion. The analyses did indicate a 40% to 50% likelihood of aspirin being significantly better than ticlopidine in reducing the risk of recurrent stroke if the trial continued to completion.
“The decision of the data and safety monitoring board to stop the study was based on the potential futility of ticlopidine use for the primary study outcome end point and the small likelihood, but potential for serious adverse events among ticlopidine-treated patients,” stated the researchers in their article which was published in the June 11, 2003 issue of the Journal of the American Medical Association.*
After 6.5 years of follow-up, 106 patients in the ticlopidine group experienced a subsequent stroke, while only 86 patients in the aspirin group had a stroke. In addition, nine of the ticlopidine patients had a heart attack compared to only eight of the aspirin patients. Each group experienced 18 “vascular deaths” during the study period.
“We thought that ticlopidine would substantially be better than aspirin in reducing recurrent strokes, heart attacks and death. We did not find that,” said study author Dr. Philip Gorelick of Rush Medical College in Chicago.
In addition, the ticlopidine group experienced slightly more serious and non-serious adverse events than the aspirin group (29.9% versus 28.9% overall). Of the ticlopidine patients, 3.4% developed significantly low white blood cell counts, compared to only 2.2% of patients in the aspirin group. Diarrhea was reported slightly more often in the ticlopidine group than the aspirin group (0.3% versus 0.2%). However, major gastrointestinal tract bleeding occurred more frequently among the aspirin group (0.9% versus 0.4%).
Aspirin is much less expensive than ticlopidine. A month’s supply of ticlopidine could easily exceed $100, while aspirin costs only pennies per day. In addition, blood tests must be performed every two weeks during the first three months of use of ticlopidine, adding further to the expense and inconvenience.
“Aspirin is much less expensive than other major antiplatelet agents, is readily available, easy to use, and relatively safe,” concluded the researchers. “Head-to-head comparison with other agents indicates that it may be difficult to outperform aspirin as a stroke prevention therapy in some noncardioembolic ischemic stroke patients.”
“Our data call into question the superiority of the thienopyridine ticlopidine in black non-cardioembolic ischemic stroke patients, and suggest that ticlopidine is unlikely to be superior to aspirin for prevention of recurrent stroke and major vascular events in these patients. Furthermore, ticlopidine may have a less favorable and potentially serious adverse event profile. Therefore, aspirin is a reasonable first choice prevention agent in aspirin-tolerant black patients with noncardioembolic ischemic stroke.”
— Marc Ellman, M.D.