Aspirin and Antiplatelet Medications (cont.)
Treatment of exertional and unstable angina
Aspirin is particularly useful in preventing heart attacks
and heart attack related deaths in patients with
unstable angina. The Canadian Multicenter Trial, and the
Montreal Heart Institute study all demonstrated significant reductions
(approximately 50%) in the risk of heart attack among patients with unstable
angina who are treated with aspirin. A study by the Research on
Instability in Coronary Artery Disease Group (RISC) showed a 70% reduction in
the risk of death or heart attack in patients with unstable angina treated with
aspirin. Aspirin usually is started as soon as the diagnosis of unstable angina is made and then continued
indefinitely.
In patients with prolonged chest pain due to unstable
angina (a situation in which heart attacks are frequent), percutaneous
transluminal coronary artery angioplasty (PTCA) with or without stenting may be
necessary to open blocked coronary arteries. Aspirin is often used in
combination with another antiplatelet agent, such as
eptifibatide (Integrilin),
and an anti-coagulant (heparin or low molecular weight heparin) to prevent heart attacks while
awaiting the PTCA procedure. Aspirin then is used long-term (either alone or in
combination with another antiplatelet agent) to prevent blood clots from forming
inside the coronary arteries and stents.
In patients with exertional angina (chest pain brought on by exertion), low
dose aspirin (75 mg-325 mg daily) given long-term has been shown to
significantly reduce the risk of heart attacks, sudden death, and ischemic
strokes.
Treatment of ischemic strokes
Ischemic stroke is a process similar to a heart attack. In general, ischemia means injury
to a tissue in the body due to lack of blood flow. Accordingly, an
ischemic
stroke is injury to the brain tissue due to lack of blood perfusion. This
usually happens because of atherosclerosis (narrowing and hardening of the blood
vessels) of the arteries in the brain. Heart attack is the ischemia of the heart
caused by similar process. Another major process for ischemic stroke may be due
to an embolism (a blood clot that dislodges and travels from some other
location in the body) to the blood vessels in the brain stopping blood from
passing through the blood vessel.
When aspirin at moderate doses (160-350 mg/d) is given to
patients as soon as an ischemic stroke is recognized (usually within the first
48 hours of the onset of symptoms), survival is improved, and the risk of
additional strokes is reduced. Aspirin is believed to benefit patients having
acute ischemic strokes by preventing the propagation (extension or growth) of
the blood clots and preventing the complete obstruction of the arteries.
However, aspirin is not effective in treating or preventing hemorrhagic strokes. In fact, some studies
suggest that long-term aspirin use may increase slightly the risk of developing
hemorrhagic strokes.
It is important to recognize that aspirin is not the
preferred treatment for ischemic strokes. Thrombolytic medications (medications
that dissolve clots) are used early (as soon as an ischemic stroke is
recognized) to open blocked cerebral arteries.
The major limitation for using these medications is time. For example, for an
ischemic stroke, thrombolytics must be given within the first three hours after
the first symptoms of a stroke. Many people with strokes may not recognize the
symptoms and may delay medical attention for several hours if not days after the
onset of stroke symptoms.
Another limitation in their use is that only certain patients qualify to
receive these medications. As a result, for patients in whom thrombolytic
medications cannot be used (most often because of underlying conditions that can
cause excessive bleeding), doctors may consider using aspirin. Thus, aspirin is
often the drug that patients with stroke will receive when they are seen in the
emergency room.
Prevention of strokes
Patients with prior strokes and TIAs (mini-strokes) usually have significant
atherosclerosis of the carotid and /or the smaller arteries within the brain and
are at risk of further strokes. (These patients often have coronary
atherosclerosis as well and are at risk for heart attacks.) Long-term
low-to-moderate doses of aspirin (50-325 mg/d) have been found to reduce the
risk of strokes as well as heart attacks in these patients.
Aspirin is not the only medication to prevent strokes among patients with
atherosclerosis. Another anti-platelet agent, clopidogrel (Plavix), also has
been used, especially in patients who are intolerant or allergic to aspirin.
Aspirin is sometimes combined with a second anti-platelet agent, dipyridamole
(Persantine, Aggrenox), to prevent strokes.
Antiplatelet agents are not the only measures that prevent
strokes. For example, aspirin alone may not be sufficient to prevent embolic
strokes in patients at risk for these strokes, such as in patients with
atrial
fibrillation. In these patients, warfarin (Coumadin), an oral anti-coagulant
that is a stronger anti-clotting medication than aspirin, may be necessary.
In patients with ischemic strokes or TIAs who have advanced atherosclerosis
and narrowing of the carotid arteries, carotid endarterectomy (a surgical
procedure to widen the narrowed carotid artery, the main blood vessel feeding
the brain) or the introduction of stents within the carotid artery may be
necessary to prevent strokes.
How effective is aspirin for preventing heart attacks among healthy subjects?
Long-term, low dose aspirin (75-160 mg/d) infrequently
causes serious side effects. Therefore, among patients with advanced
atherosclerosis (patients who already have heart attacks and strokes, patients
with angina or TIAs, patients who need PTCA and coronary artery bypass surgery,
and patients with symptoms of peripheral vascular disease) the benefits of low dose aspirin usually outweigh
the risks of long-term aspirin (discussed below).
Unlike the treatment of patients with advanced atherosclerosis, aspirin use
among healthy subjects (for example, individuals with no prior heart attacks or
strokes) is more controversial. In the U.S. Physicians' Health Study (a study
comparing 325 mg of aspirin every other day to placebo among more than
20,000 healthy male doctors), there were fewer heart attacks among aspirin users
as compared to placebo users. However, the overall rate of death from heart
disease
was no different between aspirin users and men on placebo. Furthermore, there is
insufficient data to evaluate the benefit of aspirin among healthy women.
Therefore, the potential benefits of long-term aspirin in
healthy subjects may not justify the small risks of serious side effects of
aspirin, including bleeding from ulcers and blood vessels in the brain. Healthy
individuals should discuss long-term therapy with aspirin with their doctors before they start
taking aspirin. Most doctors recommend aspirin in healthy subjects who have one
or more risk factors for developing atherosclerosis.
What are the latest recommendations on the use of aspirin
in the primary prevention of cardiovascular disease?
As described below, the recommendations for the secondary prevention (in
people who already have had a heart attack or stroke) of future attacks are more
compelling.
In 2009, the U.S. Preventive Services Task Force (USPSTF) has come up with
slightly modified recommendations for the primary prevention of cardiovascular
disease using aspirin. Based on their review of the published data:
- They
encourage the use of aspirin in men between 45-79 years of age and women between
55-79.
- In individuals older than 80, the treatment with aspirin was associated
with more bleeding episodes which outweigh the protective benefits.
- In men
younger than 45 and women younger than 55, the benefits of aspirin seemed to too
insignificant to warrant routine use for the prevention of cardiovascular
disease.
Next: How effective is aspirin for preventing heart attacks among healthy subjects? »
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