ASPIRIN AND HEART DISEASE OVERVIEW

Aspirin is a nonsteroidal antiinflammatory drug (NSAID) that has been used at moderate to high doses to decrease pain and reduce swelling. More recently, low dose aspirin has been used to treat and prevent cardiovascular disease (CVD).

Cardiovascular disease includes conditions such as heart attack, stroke, and peripheral artery disease (poor circulation) in the legs; these conditions cause more than 900,000 deaths each year in the United States alone.

Many large trials have shown that aspirin has benefits for the following groups:

• Virtually all people who have had a heart attack, stroke, or peripheral artery disease, as well as angina, stents, or bypass surgery
• Men and women who have no signs or symptoms but have an increased risk of a first heart attack (eg, due to diabetes or other risk factors)

However, the benefits of aspirin must be weighed against its possible side effects. People with a higher risk of heart attack have a greater potential for benefit. Thus, it is important to discuss the overall risk of cardiovascular disease with a healthcare provider to determine if aspirin could be of benefit.

ACTIONS OF ASPIRIN

Aspirin inhibits the clumping of platelets (even in low doses), has pain killing effects (in medium doses), and has antiinflammatory effects (in high doses).

Platelets are tiny cell fragments circulating in the blood that have a role in blood clotting. Under normal circumstances, platelets clump together and help form blood clots that stop bleeding. However, in coronary heart disease, platelets clump together in narrowed arteries, which leads to the development of a clot within the artery; the platelet "plug" itself and/or the clot that forms can block blood flow (figure 1).

This blockage can have significant consequences. When the arteries that supply blood to the brain are blocked, the supply of oxygen to the brain is decreased. The consequences of this depend upon the duration and the extent to which blood flow is cut off.

• When the arteries that supply blood and oxygen to the heart are blocked briefly, the result is an episode of chest pain, called angina. A blockage that is of longer duration can result in a heart attack (also called myocardial infarction).
• In the brain, when the blockage is brief, the result is a transient ischemic attack (TIA), and when the blockage is longer, the result is an ischemic stroke. (See "Patient information: Stroke symptoms and diagnosis (Beyond the Basics)".)

BENEFITS OF ASPIRIN

The benefits of aspirin have been studied in a wide range of patients, including the groups discussed below.

Prevention of heart attack or stroke — Several large trials, primarily among men, have shown that aspirin can prevent a first heart attack in people who have no signs or symptoms of cardiovascular disease (this is called primary prevention). However, these trials could not detect the effects of aspirin on the risk of stroke and death related to cardiovascular disease. In one trial of women, aspirin reduced the risk of a first stroke and also decreased the risk of a first heart attack among those 65 years and over [1].

The risk of a first heart attack or stroke in healthy men and women is far lower than among those who are having or have had an event. As a result, the benefit of reducing the risk of a first heart attack must be weighed against risks, such as gastrointestinal bleeding and other side effects. (See 'Side effects of aspirin' below.)

Expert groups recommend aspirin to prevent heart attack or stroke for healthy men and women when the benefits outweigh the risks; this includes people with a 10-year risk of a coronary event of at least 6 to 10 percent. The 10-year risk can be calculated here for women (calculator 1) and for men (calculator 2).

For healthy men and women at low risk of a first event, the benefit of aspirin (prevention of heart attacks or strokes) is similar to the risk of harm (gastrointestinal bleeding). Thus, it is important to discuss your absolute benefits of aspirin on a first heart attack or stroke and your risks of aspirin with your healthcare provider.

The recommended daily dose of aspirin for prevention of heart attack and stroke is between 81 mg and 162.5 mg.

During a heart attack — Aspirin can be life-saving for people who are actively having a heart attack. Healthcare providers recommend that anyone who believes they may be having a heart attack immediately take 162 to 325 mg of plain aspirin (one half to one whole adult aspirin tablet). If only enteric coated aspirin is available then the pill should be crushed or chewed to obtain an immediate effect. (See "Patient information: Heart attack (Beyond the Basics)".)

After coronary events — Aspirin is recommended for people who have a history of the following:

• Heart attack
• Stable or unstable angina
• Coronary bypass graft surgery or percutaneous coronary intervention (angioplasty)

(See "Patient information: Heart attack recovery (Beyond the Basics)" and "Patient information: Recovery after coronary artery bypass graft surgery (CABG) (Beyond the Basics)" and "Patient information: Heart stents and angioplasty (Beyond the Basics)".)

Most healthcare providers recommend that people in this group take between 75 and 100 mg of aspirin daily.

During and after stroke — Aspirin has benefits in people who are having or have recently had an ischemic stroke or transient ischemic attack (TIA). The recommended dose for this group is 162.5 to 325 mg during and 81 to 325 mg per day after stroke. (See "Patient information: Ischemic stroke treatment (Beyond the Basics)" and "Patient information: Transient ischemic attack (Beyond the Basics)".)

Aspirin plus clopidogrel — Another antiplatelet medication (clopidogrel, Plavix®) may be recommended, in addition to aspirin, to further reduce the risk of future heart attacks and strokes. This may be suggested for people with a high risk of future cardiovascular events, including people with a prior heart attack, ischemic stroke, or symptomatic peripheral artery disease (also called claudication). (See "Patient information: Peripheral artery disease and claudication (Beyond the Basics)".)

SIDE EFFECTS OF ASPIRIN

Aspirin can have a significant benefit for people with a wide range of blockages in the heart, brain, or peripheral arteries, as well as those without prior events but who have a sufficiently high risk. However, aspirin has two main side effects: stomach upset (nausea, vomiting, heartburn, stomach pain, or ulcers) and bleeding.

Stomach upset — In one large study, approximately 4 percent of all people who took 300 mg of aspirin daily for 5 years noted stomach upset. Signs and symptoms of ulcer were far less common, although the risk of ulcers (particularly bleeding ulcers) is increased in the following settings:

• Increasing age, particularly >60 years
• Higher doses of aspirin
• Long duration of aspirin use
• A past history of gastrointestinal complications from aspirin or other NSAIDs (ibuprofen or naprosyn)
• A past history of ulcers (see "Patient information: Peptic ulcer disease (Beyond the Basics)")
• Current use of steroids (eg, prednisone), anticoagulants (such as warfarin), or other NSAIDs

To help prevent stomach upset, aspirin should be taken with food. People with a history of ulcers or stomach upset while taking aspirin or other NSAIDs should talk with a healthcare provider before starting; several recommendations can be made, depending upon the particular circumstances:

• The dose may be reduced
• An enteric-coated (EC) or buffered formulation may be recommended
• A medication may be given to reduce stomach acid
• Testing for a microorganism called H. pylori, which can cause ulcers, may be done (see "Patient information: Helicobacter pylori infection and treatment (Beyond the Basics)")

For patients who cannot tolerate aspirin, other antiplatelet medications, especially (clopidogrel [Plavix®] but also ticlopidine [Ticlid®]) are available. In certain circumstances , an oral anticoagulant (blood-thinning) drug, such as warfarin (Coumadin®), may be recommended in addition to or as an alternative to aspirin. The risks of bleeding are further increased when another antiplatelet agent or an anticoagulant are added to aspirin. (See "Patient information: Warfarin (Coumadin) (Beyond the Basics)".)

Bleeding — Individuals who take aspirin regularly may bleed more than usual after a cut or a nose-bleed. This type of bleeding usually causes no significant problems. Of bigger concern is when bleeding occurs in other areas, most commonly in the gastrointestinal tract (such as a bleeding ulcer), or extremely rarely, in the brain (hemorrhagic stroke). For these reasons, the benefits of aspirin must be weighed against the risks.

Because the effects of aspirin on bleeding last for about a week, it is important to notify a healthcare provider or dentist about aspirin use before any surgery or procedure. In most cases, aspirin should be stopped 7 to 10 days before a scheduled surgery or procedure.

Interaction with ibuprofen — As mentioned above, taking aspirin and another NSAID (such as ibuprofen) at the same time can increase the likelihood of stomach upset. There is also some evidence that therapy with ibuprofen can interfere with the ability of aspirin to stop platelets from sticking together. For these reasons it seems prudent to take aspirin at least two hours before ibuprofen.

There is also some evidence that therapy with ibuprofen can interfere with the protective effect of aspirin on cardiovascular disease. Patients should speak to a healthcare provider about this interaction if they require long-term ibuprofen therapy.

IS ASPIRIN RIGHT FOR ME?

You and your healthcare provider must balance the benefits of aspirin against the potential risks. As general rules:

• Aspirin has a clear benefit in people with a current or past history of heart attack, angina, ischemic stroke, transient ischemic attack, peripheral artery disease (claudication), as well as people with a 10-year risk of having a coronary event of at least 6 to 10 percent. The 10-year risk can be calculated here for women (calculator 1) and for men (calculator 2).
• Aspirin is likely to have a benefit in people with a moderate to high risk of heart attack or ischemic stroke (stroke caused by blockage of arteries that supply blood to the brain).
• The benefits of aspirin may not outweigh the risks in people who have a low risk of heart attack or ischemic stroke.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient information: Medicines after an ischemic stroke (The Basics)
Patient information: Medicines after a heart attack (The Basics)
Patient information: Coronary heart disease (The Basics)
Patient information: Heart attack recovery (The Basics)
Patient information: Lowering the risk of having another stroke (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient information: Stroke symptoms and diagnosis (Beyond the Basics)
Patient information: Heart attack (Beyond the Basics)
Patient information: Heart attack recovery (Beyond the Basics)
Patient information: Recovery after coronary artery bypass graft surgery (CABG) (Beyond the Basics)
Patient information: Heart stents and angioplasty (Beyond the Basics)
Patient information: Ischemic stroke treatment (Beyond the Basics)
Patient information: Transient ischemic attack (Beyond the Basics)
Patient information: Peripheral artery disease and claudication (Beyond the Basics)
Patient information: Peptic ulcer disease (Beyond the Basics)
Patient information: Helicobacter pylori infection and treatment (Beyond the Basics)
Patient information: Warfarin (Coumadin) (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Aspirin: Mechanism of action, major toxicities, and use in rheumatic diseases
Benefits and risks of aspirin in secondary and primary prevention of cardiovascular disease
Overview of primary prevention of coronary heart disease and stroke
Secondary prevention of cardiovascular disease

The following organizations also provide reliable health information.

• National Library of Medicine

     (www.nlm.nih.gov/medlineplus/healthtopics.html)

• National Heart, Lung, and Blood Institute

     (www.nhlbi.nih.gov/)

• American Heart Association

     (www.americanheart.org)

• The National Coalition for Women with Heart Disease

     (www.womenheart.org/)

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