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Aspirin resistance: Bad news for patients and doctors!
Aspirin is the safest, oldest and probably the most widely used cardiovascular drug and least expensivedrug in existence. Aspirin is being used from the ancient time. Even in 400 BC there is history of use of aspirin. In the 20th century, aspirin attracted the attention of physicians interested in cardiovascular disease after it was found it blocks 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, cyclooxygenase, that involves in producing thromboxane, a substance that induces platelets to clump.
Doctors always prescribe Aspirin to patients suffering from cardiovascular or cerbrovascular diseases. Many people take aspirin regularly to help prevent heart attacks and strokes. The number in our country is also very high. The American Heart Association recommends aspirin use for patients who have had a myocardial infarction (heart attack), unstable angina, ischemic stroke (caused by blood clot) or transient ischemic attacks (TIAs or "little strokes"), if not contraindicated. This recommendation is based on sound evidence from clinical trials showing that aspirin helps prevent the recurrence of such events as heart attack, hospitalisation for recurrent angina, second strokes, etc. (secondary prevention). Studies show aspirin also helps prevent these events from occurring in people at high risk (primary prevention).
But new evidence suggests that for many of those patients, 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. (New York Times, 20 July 2004). Study published in the British Medical Journal (28 Feb 2004) showed that aspirin fails to preventmost (at least 75 percent) serious vascular events in patients with symptomatic atherothrombosis. Aspirin resistance may be a cause of recurrent ischaemic vascular events in patientstaking aspirin whichmeans that aspirin does not inhibit their blood from clotting, as it is supposed to. We heard about antibiotic resistance a lot, now it is aspirin resistance! It is a bad news for lot of patients and also for the doctors, who confidently prescribe the drug. Why aspirin resistance occurs?
The causes of aspirin resistance are not known. Experts say other mechanisms in the body can cause platelet to clump besides the one that aspirin interrupts. Genetic variations may explain why some patients are resistant. 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 synthesised, mysteries remain about the pill that millions of people pop without a second thought.
Do we need test for Aspirin Resistance?
There are several different laboratorytests of platelet function, which are being used to diagnose aspirin resistance, and each has its own limitations. 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.
Although some experts have known about aspirin resistance for years, it is a topic of growing interest as studies have confirmed that aspirin users who are resistant have a higher rate of heart attacks and strokes than nonresistant aspirin users. New tests make it far easier than in the past to measure response to aspirin.
Experts say, it is not clear what to do for aspirin-resistant patients. Should aspirin be dropped? Should the doses be increased? Should
patients be switched to other anticlotting drugs? 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, New York, 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 why 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.
In a Canadian study of 967 patients, published in journal "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.
What to do if a patient has aspirin resistance?
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 (poor compliance) or taking inadequate dose or might be taking ibuprofen/indomethacin, painkillers that can interfere with aspirin's cardiovascular protection.
Patients taking coated aspirin to minimise stomach irritation may not be absorbing enough of it into the bloodstream. A study led by Dr Mark J Alberts, director of the stroke programme at Northwestern University, Chicago, USA, found that 65 percent of those taking the coated aspirin tested resistant, as against 25 percent of the people taking the uncoated type. In Bangladesh, doctors usually prescribe coated aspirin to prevent the side effects, specially the gastro-intestinal bleeding.
Is there any risk if we increase the dose of Aspirin?
Some doctors hold opinions that higher doses do not provide extra protection. The biggest fear is that doubling the dose 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.
Doctors have different opinion
Some doctors in the USA opined that they would advise their patients not to drop aspirin even if they were resistant. This is because 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. Dr Timothy G Jayasundera, Assistant Professor at the Temple University School of Medicine, Philadelphia, USA 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. Of course, studies are also finding that people can be nonresponsive to Plavix.
Re-thinking before taking or prescribing aspirin
Though aspirin is the most common cardiovascular drug in the world, we still do not know everything about aspirin that we probably ought to. It is time to re-think before taking aspirin or prescribing it. While awaiting the development of a reliable test and effectivetreatment for aspirin resistance, the most efficient strategyfor clinicians to prevent aspirin failure is to make sure that the index event was atherothro-mbotic in origin, use an appropriatedose of aspirin (75-150 mg daily), maintain a high level of compliance, and avoid combining aspirin with drugs such as ibuprofen that may reduce its effectiveness for the prevention of atherothromboticvascular events
The writer is Product Planning Officer in Beximco Pharmaceutical, currently in study leave for pursuing her Ph.D. in Clinical Pharmacology in the School of Medical Sciences, Universiti Sains Malaysia.