April 3, 2009 -- The anticlotting drug Plavix was in the news again this week, with researchers reporting that the drug helped to prevent strokes and heart attacks in people who suffer from a common heart rhythm disorder that puts them at risk for stroke.
The researchers studied over 7,500 people with atrial fibrillation. Over a nearly four-year period, those who took Plavix and aspirin were 11% less likely to suffer an "event" -- heart attack, stroke, blood clot, or death due to cardiovascular disease -- than those who took aspirin alone.
Findings of the study, called ACTIVE-A, were presented at the annual meeting of the American College of Cardiology (ACC). They were also published online by the New England Journal of Medicine.
Millions of Americans who have had stents implanted to open up clogged arteries already take Plavix. The new findings do not affect these people, but open up a potential new use for the drug.
WebMD looked into many common questions about Plavix. Here is what we found.
What is Plavix?
Plavix is an anti-platelet drug. It discourages the formation of blood clots, which helps prevent heart attacks and strokes caused by clots.
Why is Plavix given after stent implantation?
Stents are tiny mesh tubes used to prop open an artery after a balloon angioplasty opens a clog.
Bare-metal stents sometimes clog. Newer, drug-coated (or drug-eluting) stents also clog, although not nearly as often. But they take much longer to heal -- increasing the risk of a deadly blood clot forming at the site of the stent.
Blood-thinning treatment with a combination of Plavix and aspirin is given to help prevent these clots in people given stents.
Does Plavix treatment carry risks?
A chief risk is bleeding, says American Heart Association spokesman Jonathan Halperin, MD, director of clinical cardiology services at the Cardiovascular Institute at Mt. Sinai Medical Center in New York City.
Bleeding is often occult, or hidden, he says. Signs of bleeding that should immediately be reported to your doctor include dark or bloody urine; black, tarry stools; and easy, unusual bruising.
Bleeding can also lead to anemia, with symptoms of weakness and fatigue.
Your doctor can perform occult blood stool tests and blood tests to find out if you suffer from occult bleeding and/or anemia.
Other side effects of Plavix include diarrhea and allergic reactions that can cause rash or hives.
How long should people with drug-coated stents take Plavix?
There's been a big debate about this in recent years. Originally, the FDA recommended that people take Plavix, in combination with aspirin, for three to six months after stent implantation. Then, some studies suggested that people who stopped taking Plavix/aspirin treatment after three to six months had higher rates of heart attack and death than those who continued to take it. As a result, many doctors recommended that people stay on Plavix unless there was a reason to stop taking it.
The most recent evidence suggests that Plavix/aspirin treatment should be continued for two to three years after stent implantation, Halperin says.
"At that point, most doctors now recommend stopping dual therapy and switching to either Plavix or aspirin alone. The risk of bleeding -- the major side effect of aspirin as well as Plavix -- is much higher with both drugs than with one," he tells WebMD.
Halperin says that if a patient can afford it, he recommends dropping the aspirin and continuing on Plavix. A large study of nearly 20,000 people with cardiovascular disease suggested that "Plavix was slightly but significantly better than aspirin at preventing heart attacks, strokes, or deaths," he says. Aspirin is very effective as well, Halperin says.
Plavix costs about $4 a day.
Did the new ACTIVE-A study look at people with stents?
No. It looked at people with atrial fibrillation.
What is atrial fibrillation?
A-fib, as it's often called, is the most common heart rhythm disorder, affecting about 2.2 million Americans. It occurs when electrical impulses do not travel in an orderly fashion through the upper parts of the heart resulting in an irregular heart rhythm.
As a result, blood does not flow through the upper chambers of the heart as it should. This allows blood to pool and form clots that can travel to the brain, causing a stroke.
People with atrial fibrillation face five times the risk of stroke as the general population, according to Halperin. The risk increases with age.
What is the usual treatment for preventing stroke in people with atrial fibrillation?
That depends on the risk of developing stroke, Halperin says.
In people with A-fib, the risk of stroke varies according to a number of factors, he explains. They include age over 75 and the presence of other conditions, including high blood pressure, diabetes, and previous stroke.
Aspirin is generally the treatment of choice for people with A-fib and no risk factors. It reduces the risk of stroke by 22%.
For people at higher risk for stroke, the blood thinner warfarin, also sold as Coumadin, is the treatment of choice. It lowers the risk of stroke by another 38%, compared with aspirin, says ACTIVE-A study head Stuart Connolly, MD, director of cardiology at McMaster University in Hamilton, Ontario.
Why isn't everyone with atrial fibrillation given warfarin, if it's more effective at preventing stroke?
"It's a very difficult drug to take," Halperin says. For starters, it carries a major risk of potentially life-threatening bleeding. Also, many drugs, including aspirin and some antibiotics, and supplements, including fish oil, can have a dangerous interaction with warfarin.
Several surveys indicate that only half of patients with A-fib who are at increased risk of stroke take warfarin, says Aaron D. Kugelmass, MD, chairman of the committee that chose to which studies to highlight at the ACC meeting and director of the cardiac catheterization lab at Henry Ford Hospital in Detroit.
What happened in the ACTIVE-A study?
The ACTIVE-A study enrolled 7,554 people with atrial fibrillation in the U.S. and 32 other countries who were at high risk of stroke, but who could not or chose not to take warfarin.
All took aspirin daily; half also were given 75 milligrams of Plavix a day.
Over a median of 3.6 years, 924 people taking aspirin alone suffered a heart attack, stroke or blood clot or died of cardiovascular disease. In contrast, only 832 people who also took Plavix suffered one of these events.
However, people on the combination treatment were more likely to suffer a major bleed: There were 251 cases vs. 162 cases among those on aspirin alone.
The bottom line: "For every 1,000 patients treated for three years, combination treatment prevents 28 strokes, 17 fatal or disabling, and six heart attacks. This would come at a cost of 20 serious bleeds, three fatal," says study researcher Stuart Connolly, MD, director of cardiology at McMaster University in Hamilton, Ontario.
The study was funded by Sanofi-Aventis and Bristol-Myers Squibb.
So should all people with atrial fibrillation at risk of stroke now take Plavix?
No. "Patients are doing well on warfarin should not be switched; they have a superb outcomes on warfarin," Connolly stresses.
But patients who can't tolerate warfarin clearly do better on Plavix plus aspirin than on aspirin alone, he says.
Will the new study result in a change in treatment guidelines?
Connolly thinks so. "Plavix is not yet approved or part of the guidelines for treating atrial fibrillation [in people who can't take warfarin]. But I expect those changes will occur," he tells WebMD.