MONDAY, March 13, 2006 (HealthDay News) -- A startling new study has doctors rethinking the practice of prescribing the blood thinner Plavix in combination with low-dose aspirin to patients at risk of a first heart attack or stroke.
The international study included more than 15,000 patients with heart disease or risk factors for heart disease. The conclusion: The tandem therapy was of some benefit to those with diagnosed heart disease, but it nearly doubled the risk of death, heart attack or stroke in patients with heart-threatening conditions such as high cholesterol and high blood pressure.
Study co-author Dr. Eric Topol, a professor of genetics at Case Western Reserve University in Cleveland and a leading U.S. heart expert, urged doctors Monday to stop prescribing Plavix (clopidogrel) plus aspirin to patients who have not had a previous heart attack or stroke.
The researchers stressed that Plavix-plus-aspirin still has a place in preventing a second heart attack or stroke, however.
"This trial was a big surprise," Topol said. "We never would have thought that in primary prevention it [the Plavix-aspirin combination] would backfire in high-risk patients."
"Any physician who is using Plavix and aspirin as a primary prevention shouldn't do that," Topol stressed. He said he wasn't sure how many doctors are using the drug combination this way, but he suspects that the number is significant.
The researchers found an excess of bleeding and deaths among the study patients at risk of heart disease who received the combination therapy, Topol said. "This was not expected."
Findings from the study, called CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance), were presented Sunday at the annual meeting of the American College of Cardiology in Atlanta. The report was also published online by The New England Journal of Medicine, to coincide with the meeting.
Funding for the trial was provided by the makers and distributors of Plavix, Sanofi-Aventis and Bristol-Myers Squibb.
In the trial, 15,603 patients in 32 countries with either cardiovascular disease or risk factors for it were randomly selected to receive Plavix plus low-dose aspirin, or a placebo plus low-dose aspirin. The patients were then followed for 28 months.
The researchers found that among patients in whom Plavix and aspirin were used to try to prevent a first heart attack or stroke, 6.6 percent of the patients died or had a heart attack or stroke, compared with 5.5 percent of the patients taking aspirin alone.
Among those receiving Plavix and aspirin, 3.9 percent died of cardiovascular disease, compared with 2.2 percent of those receiving aspirin alone, the study authors reported.
However, among patients who had diagnosed heart disease at the start of the trial, 6.9 percent of those receiving Plavix plus aspirin died or had a second heart attack or stroke, compared with 7.9 percent of those taking aspirin alone.
"Plavix didn't do well for patients in primary prevention," Topol said. "For patients with established vascular disease there was some benefit. Among these patients there was nearly a 20 percent reduction of death, heart attack, or stroke."
Topol noted that when taken alone, aspirin and Plavix have about the same benefit in preventing a first heart attack or stroke. But aspirin is much less expensive, he noted.
One expert thinks the findings should be heeded.
"It has been known or assumed that clopidogrel is useful in patients with coronary disease, particularly high-risk ones, from previous trials," said Dr. David D. Waters, the chief of cardiology at San Francisco General Hospital and a professor of medicine at the University of California, San Francisco.
"CHARISMA strongly suggests that if you don't have symptomatic coronary disease yet, the drug [Plavix] probably causes more harm than good," Waters said. "There are other useful treatments for high-risk primary prevention -- aspirin and statins for example. So, we should focus on those, and forget about clopidogrel, for these patients," he advised.
Another expert thinks the findings and others make it essential to reconsider who should be prescribed Plavix and aspirin together.
"Last year we learned that Plavix has a greater risk for gastrointestinal bleeding than previously thought," said Dr. Byron Cryer, an associate professor of medicine at the University of Texas Southwestern Medical School, Dallas.
"This year we learned that the combination of Plavix plus aspirin is not as effective for the prevention of cardiovascular events as we previously thought. In sum, this means that the benefit-to-risk ratio of Plavix has become even narrower," he said.
"Physicians will need to be even more selective in choosing appropriate patients for the aspirin/Plavix combination," Cryer said.
The National Institutes of Health can tell you more about Plavix.