The drugs aspirin and clopidogrel, which reduce the formation of blood clots, work better together than aspirin alone at reducing microembolic signals detected by transcranial Doppler. These tiny clots, or microemboli, produce no symptoms but serve as a surrogate marker for the risk of future stroke or transient ischemic attack (TIA).
In today's Circulation: Journal of the American Heart Association lead author Hugh S. Markus, FRCP, professor of neurology at St. George's Hospital Medical School in London, U.K. said, "The combination of clopidogrel and aspirin was significantly more effective at reducing blood clots than if we used aspirin alone."
The findings emerged from an international study called Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis (CARESS), a randomized, double-blind clinical trial assessing the efficacy of anti-clotting agents in reducing blood clots.
CARESS enrolled 107 participants at 11 medical centers in France, Germany, Switzerland and the United Kingdom. All patients had at least 50 percent narrowing of the carotid artery -- the main vessel carrying blood to the brain. Each had suffered a stroke or TIA within the last three months. In the study, researchers identified patients who had microscopic blood clots in a brain artery. They were given either aspirin alone or clopidogrel and aspirin daily.
Recent studies have suggested that the risk of a very early recurrent stroke after a minor stroke or TIA may be as high as 8 percent to 12 percent at seven days.
"The risk is particularly high in patients with narrowed carotid arteries, which suggests that more aggressive anti-clotting therapy may be indicated in this patient group," Markus said.
Fifty-one patients received clopidogrel and aspirin, and 56 received aspirin only for seven days. Researchers used transcranial Doppler (TCD) ultrasound for one hour on the second and seventh days of treatment to detect the microemboli in the patients' middle cerebral artery inside the brain.
CARESS is the first multi-center trial to use TCD ultrasound: a noninvasive, painless test to detect tiny clots in the bloodstream.
After seven days microscopic clots were detected in only 43.8 percent of the patients receiving the dual therapy compared to 72.7 percent of the group treated with aspirin only.
"The results demonstrate the power of the technique to detect treatment effects in relatively small groups of patients, far less than those required with the use of clinical end points such as stroke, and suggest this technique may help screen different drug combinations for further testing in large and expensive clinical trials," he said.
Besides significant differences in the presence of tiny blood clots between the two groups, the frequency of clots was also lower in the dual treatment group. The frequency per hour was reduced 61.2 percent on the seventh day in those taking both drugs compared to the aspirin-only patients.
Researchers found no significant difference in brain bleeding rates between the two groups, and no episodes of major hemorrhage in either group.
Physicians most often prescribe aspirin to prevent recurrent strokes or transient ischemic attacks caused by blood clots. However, aspirin prevents recurrent strokes in only about one-fifth of the patients treated.
"We have failed to prevent a lot of these clots using aspirin alone, so we need a better treatment," he said.
Aggressive anti-clogging therapy appears more effective in high-risk patients studied in CARESS, but additional studies are needed to confirm this finding.
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Sanofi-Synthelabo and Bristol Myers-Squibb funded the study.
Statements and conclusions of study authors that are published in the American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability. http://www.americanheart.org - DALLAS, April 26