For Some, Aspirin May Not Help Hearts
02/18/2005.
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. Barry Bertolet, interventional cardiologist with Cardiology Associates of North Mississippi.
Patients who use aspirin to fight pain or inflammation are not affected by these 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 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. Aspirin also has anti-inflammatory effects that may also stave off heart attacks.
“Aspirin resistance is associated with a worse outcome,” said Dr. Murray Estess, cardiologist with Cardiology Associates of North Mississippi. “The literature is pretty consistent about that, however, there is no convincing evidence now available that supports altering treatment is beneficial to the patient.” It is now suggested that patients found to be aspirin resistant, a higher dose of aspirin be prescribed. If that does not work, another anti-platelet drug, such as clopidogrel, should be prescribed.
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 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.
In a recent study of 326 patients with cardiovascular disease, at the Cleveland Clinic, 25 percent were found to be aspirin resistant. In that study, published last year in The Journal of the American College of Cardiology, the patients deemed resistant had three times the rate of death, heart attack or stroke compared with nonresistant patients in the subsequent two years or so.
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’ study, 28 percent of those taking a high dose were aspirin resistant, compared with 56 percent on a low dose.
Studies are also finding that people can be nonresponsive to clopidogrel. The extent of overlap between aspirin resistance and clopidogrel resistance is not clear. The causes of clopidogrel resistance, like aspirin resistance, are not yet known. In some early studies, cigarette smoking seems to promote clopidogrel resistance. Genetic variations may also explain why some patients are resistant.
“It is not surprising that aspirin does not work for everyone. Virtually no drug does.” said Barry Bertolet, MD.
The VerifyNow Aspirin test is now available at Cardiology Associates of North Mississippi. It is expected that the test for plavix resistance will be available in the first quarter of 2005.