Posted on 07/20/2004 10:18:34 AM PDT by neverdem
More than 20 million Americans take aspirin regularly to help prevent heart attacks and strokes. But new evidence suggests that for many of them, the pills do little if any good. Recent studies have found that anywhere from 5 percent to more than 40 percent of aspirin users are "nonresponsive" or "resistant" to the medicine. That means that aspirin does not inhibit their blood from clotting, as it is supposed to.
"They are taking it for stroke and heart attack prevention, and it's not going to work," said Dr. Daniel I. Simon, the associate director of interventional cardiology at Brigham and Women's Hospital in Boston and an associate professor at Harvard.
A vast majority of doctors do not test patients for aspirin resistance. Several doctors said even resistant patients would probably still be better off taking aspirin than dropping it. Also, people who use aspirin to fight pain or inflammation are not affected by the new findings.
Scientists are racing to clarify further the significance of aspirin resistance and how to counteract it. What they learn could influence how one of the oldest and most widely consumed medicines is used, perhaps leading to more customized therapies.
"You're talking about a huge number of people" who might not be benefiting, said Dr. Michael J. Domanski, head of the clinical trials unit of the National Heart, Lung and Blood Institute.
Although some experts have known about aspirin resistance for years, it is a topic of growing interest as studies have confirmed that aspirin takers who are resistant have a higher rate of heart attacks and strokes than nonresistant aspirin users.
"Aspirin resistance is associated with a worse outcome,"' Dr. Deepak L. Bhatt, director of the interventional cardiology fellowship program at the Cleveland Clinic, said. "The literature is pretty consistent about that."
New tests make it far easier than in the past to measure response to aspirin. Companies selling such tests are calling attention to aspirin resistance to help in their marketing.
Some experts caution that not enough is understood about the meaning of resistance to justify routine tests. Moreover, the experts say, it is unclear what to do for aspirin-resistant patients. Should aspirin be dropped? Should the doses be increased? Should patients be switched to other anticlotting drugs?
"For none of these tests is there evidence that altering treatment is beneficial to the patient," said Dr. Alan D. Michelson, director of the center for platelet function studies at the University of Massachusetts. "I don't think doctors should do these tests, and I don't think they should change treatments based on these tests."
A small but growing number of doctors are starting to test patients. They argue that even without conclusive evidence it is reasonable to alter therapy rather than have a patient continue to take a drug that a test shows is ineffective.
Dr. Mark A. Goodman, president of Cardiovascular Medical Associates in Garden City, N.Y., said he tested all his patients and found that 20 to 25 percent were aspirin resistant. For those people, Dr. Goodman said, he first tries a higher dose, because that is the least expensive alternative.
If that does not work - and it usually does not - he prescribes another anticlotting drug, Plavix, that can cost $3 or more a day, compared with pennies a day for aspirin.
Aspirin resistance could be one reason many people continue to have heart attacks and strokes even though they take aspirin. But, experts said, it is quite likely that some people have heart attacks or strokes even if aspirin is providing the desired anticlotting effect.
It is widely believed that the main way aspirin provides cardiovascular protection is by blocking the ability of platelets in the blood to stick together, a vital step in forming clots that can lead to a heart attack or stroke. Aspirin blocks an enzyme, cyclo-oxygenase, that is involved in producing thromboxane, a substance that induces platelets to clump.
The standard test of how readily platelets clump is called aggregometry. It is usually performed in a specialized laboratory and can take two to three hours.
New tests are far less cumbersome, allowing doctors themselves to measure aspirin resistance. Accumetrics, a small company in San Diego, received clearance from the Food and Drug Administration last year for its VerifyNow test, a version of aggregometry that doctors can perform in their own offices.
A tube of blood is collected from the patient's arm, allowed to settle for about half an hour and is then inserted with a test cartridge into a $5,000 desktop machine. The result is ready in minutes.
Dade Behring of Deerfield, Ill., a large manufacturer of diagnostic instruments, sells a blood test called the PFA-100 that works somewhat differently but that doctors say is also easy to use.
An alternative to blood testing is a urine test that measures thromboxane, the clot-inducing substance that aspirin is supposed to block. Creative Clinical Concepts of Denver has developed such a test, AspirinWorks. With that test, doctors have to send urine samples to a laboratory for testing.
The tests range in price from $30 for the Accumetrics test to $100 or more for the others.
Which test is best is still unclear. Indeed, one reason some experts say the tests are not ready for everyday use is that they can give different answers. That is one reason for the wide variation in estimates of how many people are aspirin resistant.
In a study of 326 patients with cardiovascular disease, at the Cleveland Clinic, 9.5 percent were found to be resistant using the PFA-100 test. With the older aggregometry test, 5 percent were resistant and 24 percent partly resistant.
In that study, published last year in The Journal of the American College of Cardiology, the patients deemed resistant by the aggregometry test had three times the rate of death, heart attack or stroke compared with nonresistant patients in the subsequent two years or so. But the patients deemed resistant by the PFA-100 test did not have a significantly higher incidence of problems afterward.
In a Canadian study of 967 patients published in Circulation in 2002, the quartile of patients who were most resistant, as measured by the urine test, had an 80 percent higher rate of stroke, heart attack or death from cardiovascular causes in the next five years than the quartile of patients who were most responsive. The rate of death alone was three and a half times as great.
Such results are convincing some doctors that aspirin resistance does raise risk. The next question, however, is what to do about it.
Experts say the first thing is to rule out some simple explanations why a person's blood might not be showing the anticlotting effect of aspirin. The patient might not really be taking the aspirin regularly or might be taking ibuprofen, a painkiller that can interfere with aspirin's cardiovascular protection.
Patients taking coated aspirin to minimize stomach irritation may not be absorbing enough of it into the bloodstream. A study led by Dr. Mark J. Alberts, director of the stroke program at Northwestern University, found that 65 percent of those taking the coated aspirin tested resistant, as against 25 percent of the people taking the uncoated type.
There is some evidence that increasing the dose may help. In Dr. Alberts's study, 28 percent of those taking a high dose were aspirin resistant, compared with 56 percent on a low dose.
Other doctors say the overwhelming evidence is that higher doses do not provide extra protection. "My biggest fear is that people will be doubling the dose," said Dr. Steven R. Steinhubl, director of cardiovascular research and education at the University of Kentucky. "We might just end up doubling the side effects and not end up helping the patients."
The side effects of aspirin include gastrointestinal bleeding and an increased risk of a type of stroke caused by bleeding in the brain. Some doctors say people who receive an anticlotting effect from aspirin would probably not be at risk for such side effects.
Other doctors say that is not at all clear.
Some doctors interviewed said they would not have patients drop aspirin even if they were resistant; aspirin has anti-inflammatory effects that may also stave off heart attacks, even if the anticlotting effect is absent.
Some doctors said they might drop aspirin if a patient switched to Plavix, which inhibits platelets by a different mechanism from aspirin's. Plavix, known generically as clopidogrel, is jointly marketed by Sanofi-Synthélabo and Bristol-Myers Squibb.
Dr. Timothy G. Jayasundera, assistant professor at the Temple University School of Medicine, said he found that in patients undergoing angioplasty and stenting to open clogged arteries he could overcome aspirin resistance by giving intravenous antiplatelet drugs during and immediately after the procedure and then have patients take Plavix long term.
Louis Cancelliere, a worker in a fruit store in Philadelphia who was in Dr. Jayasundera's study, found out about aspirin resistance the hard way. Mr. Cancelliere was found to be aspirin resistant after having a mild heart attack and receiving a stent last autumn. But his doctor took him off Plavix after 30 days and left him on aspirin alone. In March, he had another heart attack and got another stent.
Now Mr. Cancelliere, 56, is on Plavix.
"If you don't get tested, you could be in my boat," he said.
Still, neither Dr. Jayasundera's small study, which is yet to be published, nor Mr. Cancelliere's experience prove that adding Plavix lowers the risk of future heart attacks for aspirin-resistant people. Some studies, however, are under way to answer that question.
Of course, studies are also finding that people can be nonresponsive to Plavix. The extent of overlap between aspirin resistance and Plavix resistance is not clear.
The causes of aspirin resistance are also not known. Experts say other mechanisms in the body can cause platelets to clump besides the one that aspirin interrupts. Genetic variations may explain why some patients are resistant.
Dr. Marc Ladenheim, a cardiologist in Burbank, Calif., who has tested patients for several years, said more severe disease correlated with greater rates of aspirin resistance. Some studies have found the degree of resistance can change over time.
Scientists say it is not surprising that aspirin does not work for everyone. Virtually no drug does. Still, the emerging awareness of aspirin resistance suggests that 107 years after aspirin was first synthesized, mysteries remain about the pill that millions of people pop without a second thought.
"It's the most common cardiovascular drug in the world," Dr. Bhatt said, "and we still don't know everything about aspirin that we probably ought to."
Well thank you very much Neverdem........my stock in Bayer just dropped...........:o)
Ya could have kept this a secret darn it ! Ow chest pains !!.......
Stay safe !
It & other(dangerous & untested) herbs have given me peace & understanding of our marvelous human biochemistry.
Eat right, sleep well, work hard, take aspirin and then you die...
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