MONDAY, Feb. 4, 2002 (HealthDayNews) -- A huge scientific study has found that aspirin alone is just as effective as aspirin and the anti-clotting drug warfarin in preventing death, second heart attacks and stroke.
Both aspirin and warfarin (brand name Coumadin) have been shown to reduce a person's risk of heart attack or stroke by slowing clotting in the body's blood vessels, but each does it at different stages of the clotting process.
"They're working on two different mechanisms," says Dr. Stephen Siegel, a clinical assistant professor of cardiology at New York University School of Medicine. "Aspirin works on the platelets, which are initiating the clot, and warfarin works on a later stage of clotting."
Generally, doctors prefer aspirin because it's easy to take and costs less than warfarin. The risk is that both drugs, especially warfarin, can cause internal bleeding.
Because the two drugs worked well independently, researchers thought they would work even better together.
Unfortunately, they were wrong.
"It didn't happen," says Dr. Louis Fiore, lead investigator and an assistant professor of medicine and public health at Boston University School of Medicine and School of Public Health.
The main issue was the dosage, and the researchers say there may still be a chance the combination therapy will prove more effective with a higher dose of warfarin.
The study involved 5,050 men and women at 78 different sites, and lasted more than six years. Researchers lowered the aspirin dose to 81 milligrams -- versus 162 milligrams when taking the drug alone -- and the warfarin dose to between 1.5 and 2.5 International Units -- the standard dose is 2.5 to 3.5 International Units.
"We used a lower intensity than recommended when using warfarin alone because we thought putting them together would cause too much bleeding," Fiore explains. "In retrospect, we now think that was the mistake, that you need to use both drugs at full dose. If we did it again, we would leave aspirin at 81 milligrams and use the standard dose of warfarin."
All of the 5,050 participants had suffered a heart attack within 14 days of enrolling in the study. Each was followed for a median of 2.7 years.
When all was said and done, there were no appreciable differences between the two groups. In the segment of patients receiving the combined therapy, 17.6 percent died, compared with 17.3 percent in the aspirin-only group. In the combination group, 13.3 percent had a second heart attack versus 13.1 percent in the aspirin group. A small number -- 3.5 percent -- of patients receiving both drugs had a stroke, while a slightly smaller number -- 3.1 percent -- of aspirin-only participants suffered a stroke.
People in the combination group had nearly twice as many major bleeding episodes as the aspirin group. The bleeding, however, stayed within acceptable levels in both groups, Fiore says.
"It would have been nice if it had positive results because, at low dosages, it was a very safe combination," Fiore says. "We tried for a home run with big efficacy and low toxicity, but it was a long shot."
Fiore's initial study proposal had called for a higher dose of warfarin, but the reviewing committee refused to approve it.
HealthDay first reported the results of this study in 1999, a year after the study was closed and just after the findings were presented at an American Heart Association meeting in Atlanta. The study now appears in the Feb. 5 issue of Circulation.
Preliminary reports from two European studies, neither of which have been published, show encouraging results when higher doses of warfarin are used.
Siegel is less optimistic.
"I would be fearful [of a higher dose] because of the risk of bleeding," he says.
One of Siegel's patients is taking both warfarin and anti-platelet drugs for different problems. "I'm sweating the month out," he says.
What To Do
The American Heart Association has information on aspirin and heart disease and anticoagulant drugs, including warfarin. Also, visit the National Stroke Association.
If you want to learn more about Coumadin, visit Bristol-Myers Squibb Co..
