Coronary Artery Disease

Your heart is an amazing powerhouse that pumps and circulates 5 or 6 gallons of blood each minute through your entire body.

Understanding how the heart works

To understand heart disease, you must first know how the heart works. The heart is like any other muscle, requiring blood to supply oxygen and nutrients for it to function. It beats about 100,000 times a day, pumping blood through your circulatory system. The cycle of pumping blood throughout your body carries fresh oxygen to your lungs and nutrients to your body's tissues. Blood also takes waste, such as carbon dioxide, away from your tissues,. Without this process, we could not live.

Heart disease begins when cholesterol, fatty material, and calcium build up in the arteries, a process known as atherosclerosis.

What is heart disease?

Heart disease begins when cholesterol, fatty material, and calcium build up in the arteries. When this occurs in the arteries that supply the heart, this buildup, or plaque, causes the arteries to narrow, so that oxygen delivery to the heart is reduced. The reduction in oxygen delivery to the heart can create chest pain, also called angina.

Blockage of the coronary arteries by plaque may cause a heart attack (myocardial infarction) or a fatal rhythm disturbance (sudden cardiac arrest).

The link between heart disease and heart attack

When plaque builds up to the point that it ruptures, it causes a blood clot to form in the coronary artery. The blood clot blocks blood from flowing to the heart muscle, leading to a heart attack. In a worst-case scenario, sudden cardiac arrest or fatal rhythm disturbance can occur.

Cardiovascular disease is the leading cause of death for both men and women in the U.S.

Heart disease: the number-one killer

Heart disease affects about 14 million men and women in the United States, and it has a high mortality rate. In fact, it takes more lives than the next seven leading causes of death combined.

Some of the risk factors for heart disease include smoking, high blood pressure, high cholesterol, diabetes, and obesity.

What are the risk factors for heart disease?

Some of the common risk factors for heart disease include

• smoking,
• high blood pressure (hypertension),
• high cholesterol,
• diabetes,
• family history of heart disease,
• peripheral artery disease, and
• obesity.

Additional heart disease risk factors include lack of exercise, an unhealthy diet, stress, and a "type A" personality

What are lifestyle risk factors for heart disease?

Lifestyle risk factors that contribute to heart disease include

• lack of exercise,
• high-fat diet,
• emotional stress, and
• having a "type A" personality (aggressive, impatient, competitive).

One of the most devastating consequences of heart disease can be sudden cardiac arrest.

Sudden cardiac death - a fatal consequence of heart disease

Everyone's experience with heart disease is different. Some people experience shortness of breath or chest pain and make it to the hospital in time to be treated. Others are not as lucky. For some people, sudden cardiac arrest can be the first symptom they experience, and it is often deadly unless treated immediately.

Besides chest pain (angina) and shortness of breath, some other common symptoms of heart disease include jaw pain, back pain, and heart palpitations.

What are common symptoms of heart disease?

Symptoms of heart disease usually occur during exercise or activity. That's because the heart experiences increased demand for nutrients and oxygen that cannot be met because the coronary arteries are blocked. Other symptoms of heart disease include

• chest pain (angina),
• shortness of breath,
• jaw pain, and
• back pain, especially on the left side.

Other symptoms of heart disease may include dizziness, weakness, irregular heartbeat, nausea, and abdominal pain.

What are other symptoms of heart disease?

Other symptoms of heart disease may include

• dizziness or light-headedness,
• weakness when at rest,
• irregular heartbeat,
• nausea, and
• abdominal pain.

Women, seniors, and people with diabetes tend to experience heart disease differently than men.

What are the heart disease symptoms in women, seniors, and people with diabetes?

For many women, seniors, and people with diabetes, pain is not a symptom of heart disease at all. Instead of experiencing discomfort, they often have symptoms of malaise or fatigue.

Doctors use a variety of tests to detect heart disease. One common test is the electrocardiogram (ECG or EKG).

What is an electrocardiogram (EKG)?

A healthy heart works as an "electrical pump" and needs a strong blood supply to conduct electricity. People with heart disease, however, have a weak blood supply, so their hearts conduct electricity poorly. An electrocardiogram (EKG) is a noninvasive test that measures the electrical activity of the heart. An EKG takes approximately five minutes and is painless. Many other heart conditions can be diagnosed with an EKG, for example

• abnormal heart rhythms,
• evidence of prior heart attack,
• evidence of an evolving heart attack,
• unstable angina,
• congenital heart abnormalities,
• evidence of abnormal blood electrolytes, and
• evidence of inflammation of the heart (myocarditis, pericarditis).

Sometimes, if an electrocardiogram comes back normal, doctors will use stress tests to detect heart disease.

What is a stress test?

Symptoms of heart disease tend to show up when the person is exercising because that's when the heart needs a higher level of oxygen delivery. However, for a person with heart disease, the coronary arteries can't deliver the amount of oxygenated blood needed because of the coronary artery blockage. That's why stress tests require the patient to perform a strenuous activity under a doctor's supervision, such as walking or running on a treadmill. An EKG is taken of the person before, during, and after the stress tests. Stress tests have a 60%-70% accuracy rate for detecting blockages in the coronary arteries. If a patient is unable to walk on a treadmill, a stress test can be used with medication that mimics the physiology of exercise without the patient needing to walk, and the heart can be imaged with nuclear techniques or ultrasound, and this is as good as exercise.

Another test option is echocardiography, which uses sound waves to generate images of the heart.

What is echocardiography?

Doctors may want to use echocardiography to detect heart disease. Echocardiography uses sound waves to generate images of the heart. The test serves as a tool to see how well the heart muscle is functioning. A normal heart pushes at least 50%-60% of the blood in the ventricle out to the body when it beats. Echocardiography can show if the heart muscle is weaker than this, which could indicate heart disease.

Computerized tomography (CT) scans are used to show that heart disease is not present and that the coronary arteries are normal.

Why use computerized tomography tests (CT scans)?

Computerized tomography tests, also known as CT scans, take detailed images of blood vessels to show whether they have narrowed. In general, this test is used to show that heart disease is not present.

Coronary angiography via cardiac catheterization is considered the "gold standard" of heart disease tests.

What makes coronary angiography a superior test compared to the others?

During coronary angiography, doctors guide a catheter into the coronary arteries. Next, a small amount of radiographic contrast (a solution containing iodine, which is easily visualized with X-ray images) is injected into each coronary artery. X-ray images are then taken, which are called the angiogram. Angiographic images accurately reveal the extent and severity of all coronary arterial blockages.

Heart disease treatment is different for everyone.

There is no single treatment method for heart disease

Each person experiences heart disease differently, and no one treatment method works for everyone. A multi-faceted approach of dietary changes, lifestyle changes, exercise, and medications may be combined,, depending on the patient's individual situation and needs.

For some patients with heart disease, medications may be necessary.

What are some common medications used to treat heart disease?

Common heart disease medications can include:

• beta blockers which reduce heart rate and blood pressure;
• nitroglycerin, which dilates the coronary arteries, making it easier for blood to flow;
• calcium channel blockers, which help slow the heart rate, allowing the heart to beat more efficiently;
• ACE Inhibitors, which dilate blood vessels to increase blood flow and relieve stress on the heart; and
• statins, which reduce the number of lipids (found in cholesterol) in the blood to reduce the likelihood of plaque forming on the arteries.

When medications aren't enough, sometimes invasive procedures are used to help treat heart disease.

What are some of the procedures performed to treat heart disease?

The following are common procedures used to treat heart disease.

• Coronary (balloon) angioplasty: A thin catheter is inserted into the blocked artery with a tiny balloon on the end. When the balloon is in the spot of the blockage, it is expanded to keep the artery open so blood can flow more freely, and the catheter is removed.
• Stents: The insertion of a stent is similar to coronary angioplasty except that over the balloon is a small metallic tube (a stent) that stays in place to keep the artery open while the catheter and the balloon are removed.
• Atherectomy: A drill-like device or laser cuts away the plaque covering the arteries.
• Brachytherapy: Radiation is applied to the blockages to remove them from recurring after angioplasty.

Heart disease is a highly preventable and reversible disease. A healthy diet is a major factor in controlling heart disease.

The key to preventing heart disease is through a healthy lifestyle, starting with a healthy diet.

Although heredity is a risk factor for heart disease, and an individual cannot control this factor, other factors can be modified to decrease the risk of heart disease. What you eat can reduce your chances of developing heart disease. A heart-healthy diet includes lots of whole grains, vegetables, and fruits. Chickpeas, beans, and soy products can help lower your cholesterol as well as olive oil, garlic, and avocados. Nuts, such as almonds, walnuts, and pecans, can boost "good" cholesterol (nuts are high in calories, so limit the amount you eat). Incorporate fish and seafood into your meals a few times a week. Also, try to avoid sweets.

Other lifestyle changes that can be made to help prevent heart disease include drinking alcohol in moderation and quitting smoking.

Lifestyle changes: using alcohol in moderation and quitting smoking

To raise good cholesterol levels (HDL), it is recommended that women have only one drink per day, while men should have no more than two. In addition, smoking has been linked to heart disease, so the sooner you quit, the better. In fact, after just three years of not smoking, your risk of developing heart disease becomes equal to that of a nonsmoker.

Exercise, controlling high blood pressure and diabetes, and taking daily aspirin are more ways to reduce your chances of developing heart disease.

Lower the risk of heart disease with exercise, aspirin, and by controlling high blood pressure and diabetes.

The following steps may help reduce your risk of heart disease.

• Regular exercise strengthens the heart, lowers bad cholesterol (LDL), raises good cholesterol (HDL), and lowers blood pressure, The AHA recommends exercising at least 30 minutes of exercise at least three to five days a week.
• Control high blood pressure and diabetes: If you have diabetes, keep blood sugars under control.
• Take a low-dose aspirin daily; This can reduce your risk of heart attack.

Talk with your doctor before taking any new medications or starting an exercise program.

angina

Introduction to angina

Chest pain is a common symptom that is caused by many different conditions. Some causes require prompt medical attention, such as angina, heart attack, or tearing of the aorta. Other causes of chest pain that may not require immediate medical intervention include spasm of the esophagus, gallbladder attack, or inflammation of the chest wall. An accurate diagnosis is important in providing proper treatment to patients with chest pain.

The diagnosis and treatment of angina is discussed below, as well as the diagnosis of other causes of chest pain that can mimic angina.

What is angina, and what are the symptoms of angina?

Angina (angina pectoris - Latin for squeezing of the chest) is chest discomfort that occurs when there is a decreased blood oxygen supply to an area of the heart muscle. In most cases, the lack of blood supply is due to a narrowing of the coronary arteries as a result of arteriosclerosis.

Angina is usually felt as:

• pressure,
• heaviness,
• tightening,
• squeezing, or
• aching across the chest, particularly behind the breastbone.

This pain often radiates to the neck, jaw, arms, back, or even the teeth.

Patients may also suffer:

• indigestion,
• heartburn,
• weakness,
• sweating,
• nausea,
• cramping, and
• shortness of breath.

Angina usually occurs during exertion, severe emotional stress, or after a heavy meal. During these periods, the heart muscle demands more blood oxygen than the narrowed coronary arteries can deliver. Angina typically lasts from 1 to 15 minutes and is relieved by rest or by placing a nitroglycerin tablet under the tongue. Nitroglycerin relaxes the blood vessels and lowers blood pressure. Both rest and nitroglycerin decrease the heart muscles demand for oxygen, thus relieving angina.

Angina is classified in one of two types: 1) stable angina or 2) unstable angina.

Stable angina

Stable angina is the most common type of angina, and what most people mean when they refer to angina. People with stable angina have angina symptoms on a regular basis and the symptoms are somewhat predictable (for example, walking up a flight of steps causes chest pain). For most patients, symptoms occur during exertion and commonly last less than five minutes. They are relieved by rest or medication, such as nitroglycerin under the tongue.

Unstable angina

Unstable angina is less common and more serious. The symptoms are more severe and less predictable than the pattern of stable angina. Moreover, the pains are more frequent, last longer, occur at rest, and are not relieved by nitroglycerin under the tongue (or the patient needs to use more nitroglycerin than usual). Unstable angina is not the same as a heart attack, but it warrants an immediate visit to your healthcare provider or hospital emergency department as further cardiac testing is urgently needed. Unstable angina is often a precursor to a heart attack.

What causes angina?

The most common cause of angina is coronary artery disease. A less common cause of angina is spasm of the coronary arteries.

Coronary artery disease

Coronary arteries supply oxygenated blood to the heart muscle. Coronary artery disease develops as cholesterol is deposited in the artery wall, causing the formation of a hard, thick substance called cholesterol plaque. The accumulation of cholesterol plaque over time causes narrowing of the coronary arteries, a process called arteriosclerosis. Arteriosclerosis can be accelerated by smoking, high blood pressure, elevated cholesterol, and diabetes. When coronary arteries become narrowed by more than 50% to 70%, they can no longer meet the increased blood oxygen demand by the heart muscle during exercise or stress. Lack of oxygen to the heart muscle causes chest pain (angina).

Coronary artery spasm

The walls of the arteries are surrounded by muscle fibers. Rapid contraction of these muscle fibers causes a sudden narrowing (spasm) of the arteries. A spasm of the coronary arteries reduces blood to the heart muscle and causes angina. Angina as a result of a coronary artery spasm is called "variant" angina or Prinzmetal angina. Prinzmetal angina typically occurs at rest, usually in the early morning hours. Spasms can occur in normal coronary arteries as well as in those narrowed by arteriosclerosis.

Coronary artery spasm can also be caused by use/abuse of cocaine. The spasm of the artery wall caused by cocaine can be so significant that it can actually cause a heart attack.

What are other causes of chest pain?

In caring for patients with chest pain, the doctor distinguishes whether the pain is related to a lack of oxygen to the heart muscle (as in angina or heart attack), or is due to another process. Many conditions are considered that can cause chest pain which is similar to that of a heart attack or angina. Examples include the following:

• Pleuritis (pleurisy): Inflammation of the lining of the lungs (pleuritis) causes sharp chest pain, which is aggravated by deep breathing and coughing. Patients often notice shortness of breath, in part due to their shallow breathing to minimize chest pain. Viral infections are the most common causes of pleurisy. Other systemic inflammatory conditions, such as systemic lupus, can also cause pleurisy.
• Pericarditis: Pericarditis is inflammation of the lining around the heart. Symptoms of pericarditis are similar to that of pleuritis.
• Pneumonia: Pneumonia (bacterial infection of the lung) causes fever and chest pain. Chest pain in bacterial pneumonia is due to an irritation or infection of the lining of the lung (pleura).
• Pulmonary embolism: blood clots travel from the veins of the pelvis or the lower extremities to the lung, the condition is called pulmonary embolism. Pulmonary embolism can cause death of lung tissue (pulmonary infarction). Pulmonary infarction can lead to irritation of the pleura, causing chest pain similar to pleurisy. Some common causes of blood clots in these veins is deep vein thrombosis (prolonged immobility, recent surgery, trauma to the legs, or pelvic infection).
• Pneumothorax: Small sacs in the lung tissue (alveoli) can spontaneously burst, causing pneumothorax. Symptoms of pneumothorax include sudden, severe, sharp chest pain and shortness of breath. One common cause of pneumothorax is severe emphysema.
• Mitral valve prolapse: Mitral valve prolapse is a common heart valve abnormality, affecting 5% to 10% of the population. MVP is especially common among women between 20 to 40 years of age. Chest pain with MVP is usually sharp but not severe. Unlike angina, chest pain with MVP rarely occurs during or after exercise, and usually will not respond to nitroglycerin.
• Aortic dissection: The aorta is the major vessel delivering blood from the left ventricle to the rest of the body. Aortic dissection (tearing of the aorta wall) is a life-threatening emergency. Aortic dissection causes severe, unrelenting chest and back pain. Young adults with aortic dissection usually have Marfan's syndrome, an inherited disease in which an abnormal form of the structural protein called collagen causes weakness of the aortic wall. Older patients develop aortic dissection typically as a result of chronic, high blood pressure, in addition to generalized hardening of the arteries (arteriosclerosis).
• Costochondritis, rib fractures, muscle strain or spasm: Pain originating from the chest wall may be due to muscle strain or spasm, costochondritis, or rib fractures. Chest wall pain is usually sharp and constant. It is usually worsened by movement, coughing, deep breathing, and direct pressure on the area. Muscle spasm and strain can result from vigorous, unusual twisting and bending. The joints between the ribs and cartilage next to the breastbone can become inflamed, a condition called costochondritis. Fractured ribs resulting from trauma or cancer involvement can cause significant chest pain.
• Nerve compression: Compression of the nerve roots by bone spurs as they exit the spinal cord can cause pain. Nerve compression can also cause weakness and numbness in the upper arm and chest.
• Shingles (herpes zoster infection of the nerves): Shingles is nerve irritation from the infection, which can cause chest pain days before any typical rash appears.
• Esophageal spasm and reflux: The esophagus is the long muscular tube connecting the mouth to the stomach. Reflux, or regurgitation of stomach contents and acid into the esophagus can cause heartburn and chest pain. Spasm of the muscle of the esophagus can also cause chest pain which can be indistinguishable from chest pain caused by angina or a heart attack. The cause of esophageal muscle spasm is not known. Pain of esophageal spasm can respond to nitroglycerin in a similar manner as angina.
• Gallbladder attack (gallstones): Gallstones can block the gallbladder or bile ducts and cause severe pain of the upper abdomen, back and chest. Gallbladder attacks can mimic the pain of angina and heart attack.
• Anxiety and panic attacks: Anxiety, depression, and panic attacks are frequently associated with chest pain lasting from minutes to days. The pain can be sharp or dull. It is usually accompanied by shortness of breath, or the inability to take a deep breath. Emotional stress can aggravate chest pain, but the pain is generally not related to exertion, and is not relieved by nitroglycerin. These patients often breath too fast (hyperventilate), causing lightheadedness, numbness, and tingling in the lips and fingers. Coronary artery disease risk factors are typically absent in these patients. Since there is no test for panic attacks, patients with chest pain usually undergo tests to exclude coronary artery disease and other causes of chest pain.

Why is it important to establish the diagnosis of angina?

Angina is usually a warning sign of the presence of significant coronary artery disease. Patients with angina are at risk of developing a heart attack (myocardial infarction). A heart attack is the death of heart muscle precipitated by the complete blockage of a diseased coronary artery by a blood clot.

During angina, the lack of oxygen (ischemia) to the heart muscle is temporary and reversible. The lack of oxygen to the heart muscle resolves and the chest pain disappears when the patient rests. In contrast, the muscle damage in a heart attack is permanent. The dead muscle turns into scar tissue when healed. A scarred heart cannot pump blood as efficiently as a normal heart, and can lead to heart failure.

Up to 25% of patients with significant coronary artery disease have no symptoms at all, even though they clearly lack adequate blood and oxygen supply to the heart muscle. These patients have "silent" angina. They have the same risk of heart attack as those with symptoms of angina.

How is angina diagnosed?

The electrocardiogram (EKG) is a recording of the electrical activity of the heart muscle, and can detect heart muscle which is in need of oxygen. The EKG is useful in showing changes caused by inadequate oxygenation of the heart muscle or a heart attack.

Exercise stress test

In patients with a normal resting EKG, exercise treadmill or bicycle testing can be useful screening tools for coronary artery disease. During an exercise stress test (also referred to as stress test, exercise electrocardiogram, graded exercise treadmill test, or stress ECG), EKG recordings of the heart are performed continuously as the patient walks on a treadmill or pedals on a stationary bike at increasing levels of difficulty. The occurrence of chest pain during exercise can be correlated with changes on the EKG, which demonstrates the lack of oxygen to the heart muscle. When the patient rests, the angina and the changes on the EKG which indicate lack of oxygen to the heart can both disappear. The accuracy of exercise stress tests in the diagnosis of significant coronary artery disease is 60% to 70%. If the exercise stress test does not show signs of coronary artery disease, a nuclear agent (thallium) can be given intravenously during exercise stress test. The addition of thallium allows nuclear imaging of blood flow to different regions of the heart, using an external camera. A reduced blood flow in an area of the heart during exercise, with normal blood flow to the area at rest, signifies significant artery narrowing in that region of the heart.

Stress echocardiography

Stress echocardiography combines echocardiography (ultrasound imaging of the heart muscle) with exercise stress testing. Like the exercise thallium test, stress echocardiography is more accurate than an exercise stress test in detecting coronary artery disease. When a coronary artery is significantly narrowed, the heart muscle supplied by this artery does not contract as well as the rest of the heart muscle during exercise. Abnormalities in muscle contraction can be detected by echocardiography. Stress echocardiography and thallium stress tests are both about 80% to 85% accurate in detecting significant coronary artery disease.

When a patient cannot undergo exercise stress test because of neurological or orthopedic difficulties, medications can be injected intravenously to simulate the stress on the heart normally brought on by exercise. Heart imaging can be performed with a nuclear camera or echocardiography.

Cardiac catheterization

Cardiac catheterization with angiography (coronary arteriography) is a technique that allows x-ray pictures to be taken of the coronary arteries. It is the most accurate test to detect coronary artery narrowing. Small hollow plastic tubes (catheters) are advanced under x-ray guidance to the openings of the coronary arteries. Iodine contrast "dye" is injected into the arteries while an x-ray video is recorded. Coronary arteriography gives the doctor a picture of the location and severity of coronary artery disease. This information can be important in helping doctors select treatment options.

CT coronary angiogram

CT coronary angiography is procedure that uses an intravenous dye that contains iodine, and CT scanning to image the coronary arteries. While the use of catheters is not necessary (thus the term "noninvasive" test applies to this procedure), there are still some risks involved, including the following:

• Patients allergic to iodine
• Patients with abnormal kidney function
• Radiation exposure which is similar to, if not greater than, that received with a conventional coronary angiogram.

Nonetheless, this is generally a very safe test for most people. It is a major tool in the diagnosis of coronary artery disease in patients:

• at high risk for developing coronary disease (cigarette smokers, those with genetic risk, high cholesterol levels, hypertension, or diabetes),
• who have unclear results with exercise stress tests or other testing, or
• who have symptoms suspicious of coronary disease

What are the treatment options for angina patients?

Treatment options include:

• rest,
• medications (nitroglycerin, beta blockers, calcium channel blockers),
• percutaneous transluminal coronary angioplasty (PTCA), or
• coronary artery bypass graft surgery (CABG).

Medications

Nitroglycerin

Resting, nitroglycerin tablets (placed under the tongue), and nitroglycerin sprays all relieve angina by reducing the heart muscle's demand for oxygen. Nitroglycerin also relieves spasm of the coronary arteries and can redistribute coronary artery blood flow to areas that need it most. Short-acting nitroglycerin can be repeated at five minute intervals. When 3 doses of nitroglycerin fail to relieve the angina, further medical attention is recommended. Short-acting nitroglycerin can also be used prior to exertion to prevent angina.

Longer-acting nitroglycerin preparations, such as Isordil tablets, Nitro-Dur transdermal systems (patch form), and Nitrol ointment are useful in preventing and reducing the frequency and intensity of episodes in patients with chronic angina. The use of nitroglycerin preparations may cause headaches and lightheadedness due to an excess lowering of blood pressure.

Beta Blockers

Beta blockers relieve angina by inhibiting the effect of adrenaline on the heart. Inhibiting adrenaline decreases the heart rate, lowers the blood pressure, and reduces the pumping force of the heart muscle, all of which reduce the heart muscle's demand for oxygen. Beta blockers include:

• acebutolol (Sectral)
• atenolol (Tenormin)
• bisoprolol (Zebeta)
• metoprolol (Lopressor, Lopressor LA, Toprol XL)
• nadolol (Corgard)
• propranolol (Inderal)
• timolol (Blocadren)

Side effects include:

• worsening of asthma,
• excess lowering of the heart rate and blood pressure,
• depression,
• fatigue,
• impotence,
• increased cholesterol levels, and
• shortness of breath due to diminished heart muscle function (congestive heart failure).

Calcium Channel Blockers

Calcium channel blockers relieve angina by lowering blood pressure, and reducing the pumping force of the heart muscle, thereby reducing muscle oxygen demand. Calcium channel blockers also relieve coronary artery spasm. Calcium channel blockers include:

• amlodipine (Norvasc)
• bepridil (Vascor)
• diltiazem (Cardizem)
• felodipine (Plendil)
• isradipine (Dynacirc)
• nicardipine, (Cardene)
• nifedipine (Adalat, Procardia)
• nimodipine (Nimotop)
• nisoldipine (Sular)
• verapamil (Calan)

Side effects include:

• swelling of the legs,
• excess lowering of the heart rate and blood pressure, and
• depressing heart muscle function.

Miscellaneous anti-anginal drugs

New drugs are being studied to treat angina. In 2006, the FDA approved ranolazine (Ranexa). Because of its side effects (potential to cause abnormal heart rhythm), ranolazine is indicated only after other conventional drug treatments are found to be ineffective.

Angioplasty and coronary artery bypass surgery

When patients continue to have angina despite maximally tolerated combinations of nitroglycerin medications, beta blockers and calcium channel blockers, cardiac catheterization with coronary arteriography is indicated. Depending on the location and severity of the disease in the coronary arteries, patients can be referred for balloon angioplasty (percutaneous transluminal coronary angioplasty or PTCA) or coronary artery bypass graft surgery (CABG) to increase coronary artery blood flow.

What's new in the evaluation of angina?

A newly developed computerized x-ray scan (ultrafast CT scan) is highly accurate in detecting small amounts of calcium in the plaque of coronary arteries. If an ultrafast CT scan shows no calcium in the arteries, atherosclerotic coronary artery disease is unlikely. Ultrafast CT scanning is useful in evaluating chest pain in younger patients (men under 40 and women under 50 years old). Since young people do not normally have significant coronary artery plaque, a negative ultrafast CT scan makes the diagnosis of coronary artery disease unlikely. However, finding calcium by this method is less meaningful in older patients who are likely to have mild plaquing simply from the aging process.

Even though an ultrafast CT scan is useful in detecting calcium in plaque, it cannot determine whether the calcium-laden plaque actually causes artery narrowing and reduces blood flow. For example, a patient with a densely calcified plaque causing minimal or no artery narrowing will have a strongly positive ultrafast CT scan but a normal exercise treadmill test. In most patients who are suspected of having angina due to coronary artery disease, an exercise treadmill study is usually the first step in determining whether any plaque is clinically significant. Newer very high speed CT scanners can actually detect true coronary artery plaques and lesions similar to coronary angiography.

Magnetic resonance imaging (MRI), using magnetism and radio waves, can be used to image (produce a likeness of) the blood vessels. Currently, the larger vessels, such as the carotid arteries in the neck, can be imaged using this technique. Future software and hardware improvements may allow screening of the heart's arteries with magnetic resonance testing.

What's new in the treatment of angina and heart attacks?

Coronary arteries can close after angioplasty, causing recurrent angina or even heart attacks. One way to decrease the risk of coronary artery closure is by deploying stents to keep the arteries open. Newer drug-coated stents are being improved to significantly reduce the rate of artery closure.

Angina At A Glance

• Angina is one of many causes of chest pain.
• Angina is chest pain that is a result of inadequate oxygen supply to the heart muscle.
• Angina can be caused by coronary artery disease or spasm of the coronary arteries.
• EKG, exercise stress test, stress echocardiography, stress thallium, and cardiac catheterization are important in the diagnosis of angina.
• Treatment of angina includes rest, medications, angioplasty, and/or coronary artery bypass surgery.

Aspirin and Antiplatelet Medications

What is aspirin?

Aspirin belongs to a class of medications called nonsteroidal antiinflammatory drugs (NSAIDs). Aspirin and other NSAIDs, for example, ibuprofen (for example, Motrin, Advil) and naproxen (for example, Aleve), are widely used to treat fever, pain, and inflammatory conditions such as arthritis, tendonitis, and bursitis. Aspirin is known chemically as acetyl salicylic acid and often abbreviated as ASA.

In addition to its effects on pain, fever, and inflammation, aspirin also has an important inhibitory effect on platelets in the blood. This antiplatelet effect is used to prevent blood clot formation inside arteries, particularly in individuals who have atherosclerosis (narrowing of the blood vessels) of their arteries, or are otherwise prone to develop blood clots in their arteries.

What are antiplatelet agents?

Antiplatelet agents are medications that block the formation of blood clots by preventing the clumping of platelets. There are three types of antiplatelet agents:

1. aspirin,
   
   
2. thienopyridines, and
   
   
3. glycoprotein IIb/IIIa inhibitors.

These agents differ in the way they work, their potency (how strongly they prevent clumping), how rapidly they work, and their cost.

What are platelets?

Platelets are particles (actually, remnants of cells) circulating in the blood that are needed in order for blood clots to form. Platelets initiate the formation of blood clots by sticking together (clumping or aggregating), a process called platelet aggregation. Clumps of platelets then are further bound together by a protein (fibrin) formed by clotting factors present in the blood. The clumps of platelets and fibrin make up the blood clot.

Blood clots are important because they stop bleeding (for example, a cut or laceration on the skin). When bleeding occurs from a cut, platelets become activated and form a network by attaching to the blood vessel wall at the site of bleeding, and by also attracting other clotting factors in the blood (such as fibrin) to stop ongoing bleeding rapidly.

However, if a blood clot forms inside an artery, it blocks the flow of blood to the tissue that the artery supplies, which can damage the tissue. For example, a blood clot that forms in a coronary artery supplying blood to the muscle of the heart causes a heart attack, and a blood clot that forms in an artery supplying blood to the brain causes a stroke.

How do antiplatelet agents work?

Aspirin

Aspirin prevents blood from clotting by blocking the production by platelets of thromboxane A-2, the chemical that causes platelets to clump. Aspirin accomplishes this by inhibiting the enzyme cyclo-oxygenase-1 (COX-1) that produces thromboxane A-2. While other NSAIDs also inhibit the COX-1 enzyme, aspirin is the preferred NSAID for use as an antiplatelet agent because its inhibition of the COX-1 enzyme lasts much longer than the other NSAIDs (aspirin's antiplatelet effect lasts days while the other NSAIDs' antiplatelet effects last only hours).

Thienopyridines

In addition to thromboxane A-2, platelets also produce adenosine diphosphate (ADP). When ADP attaches to receptors on the surface of platelets, the platelets clump. The thienopyridines, for example, ticlopidine (Ticlid) and clopidogrel (Plavix), block the ADP receptor. Blocking the ADP receptor prevents ADP from attaching to the receptor and the platelets from clumping.

Glycoprotein IIb/IIIa inhibitors

The glycoprotein IIb/IIIa inhibitors, such as abciximab (Reopro) and eptifibatide (Integrilin), prevent clumping by inhibiting a different receptor on the surface of platelets, the receptor for glycoprotein IIb/IIIa. The glycoprotein IIb/IIIa inhibitors that are approved by the FDA must be given intravenously (in the veins).

What is the relative potency of the antiplatelet agents?

• Since aspirin blocks only one of the several pathways by which platelet aggregation can occur, aspirin is a weak antiplatelet agent because platelet aggregation can be stimulated via another pathway.
  
  
• Since glycoprotein IIb/IIIa inhibitors block the final common pathway for platelet aggregation (platelet aggregation is blocked regardless of the nature of the initial stimuli), glycoprotein IIb/IIIa inhibitors are the most potent antiplatelet agents. The maximal antiplatelet effect of glycoprotein IIb/IIIa inhibitors is approximately nine times that of aspirin.
  
  
• The maximal antiplatelet effect of thienopyridines is in between that of aspirin and the glycoprotein IIb/IIIa inhibitors.

How quickly do antiplatelet agents work?

Aspirin

When aspirin is given in low doses (75 mg/day), the complete inhibition of the COX-1 enzyme and hence maximal antiplatelet effect may take several days. At a dose of 160-325 mg/day, the maximal antiplatelet effect of aspirin occurs within 30 minutes. Thus, aspirin at low doses (75-150 mg/day) is used for the long term prevention of heart attacks and strokes, whereas moderate doses (160-325 mg/day) of aspirin are given in situations where an immediate anti-clotting effects are needed (such as in the treatment of acute heart attacks and unstable angina).

Thienopyridines

Like aspirin, the onset of action of clopidogrel (Plavix) is dose related. Maximal antiplatelet effect occurs several days after initiation of clopidogrel (75 mg/daily), but can occur within hours after larger doses of 300 or 600 mg. Therefore, larger doses of clopidogrel are used initially when immediate antiplatelet actions are needed (such as after placement of intracoronary stents) while the lower doses are used as maintenance.

Glycoprotein IIb/IIIa inhibitors

The glycoprotein IIb/IIIa inhibitors have a rapid onset of action. Their maximal antiplatelet effect occur within minutes after an intravenous infusion, and are used mainly in patients with unstable angina or acute heart attack (myocardial infarction).

What is dipyridamole?

Dipyridamole (Persantine IV, Persantine) is another medication that decreases platelet aggregation, though the exact mechanism of its antiplatelet action is not well understood. Dipyridamole is not commonly used in heart attack prevention, although it is sometimes used with aspirin to lessen the chance of stroke.

When is aspirin used for preventing and treating heart attacks and strokes?

Aspirin is widely used either alone or in combination with other antiplatelet agents to prevent blood clots from forming in arteries. Aspirin is used specifically in several situations including:

1. Aspirin often is prescribed in moderate doses (160-325 mg/day) for patients who are having heart attacks to limit the extent of damage to the heart's muscle (by preventing blood clot formation in the blood vessels of the heart), prevent additional heart attacks, and improve survival.
   
   
2. Aspirin often is prescribed to patients undergoing surgery to open or bypass blocked arteries, including percutaneous transluminal coronary angioplasty (PTCA) with or without placement of coronary stents and coronary artery bypass surgery (CABG). Aspirin also is prescribed on a long-term basis to prevent clotting in the stents and/or the bypassed blood vessels.
   
   
3. Aspirin often is prescribed in low doses (75-160 mg/day) on a long-term basis to patients with prior heart attacks or strokes and to patients with TIAs (transient ischemic attacks or mini-strokes) and exertional angina to prevent heart attacks and ischemic strokes.
   
   
4. Aspirin may be used in low dose (75-160mg/day) for prevention of heart attack or stroke in patients with risk factors of these conditions including longstanding diabetes, vascular disease (previous heart attack or stroke, or poor circulation to the legs), or angina.
   
   
5. Aspirin is prescribed in moderate doses (160-325 mg/day) to patients who are having unstable angina to prevent heart attacks and improve survival.
   
   
6. Aspirin is prescribed in moderate doses (160-325 mg/day) to selected patients who are having ischemic strokes to limit damage to the brain, prevent a second stroke, and improve survival.

Treatment of heart attacks

In a large multi-center study (Second International Study of Infarct Survival of the ISIS-2 trial) of patients having acute heart attacks, early treatment (within 24 hours of the onset of symptoms) with aspirin (160 mg/d) was found to reduce deaths from the heart attacks by 23%. The improved survival is believed to be due to aspirin's ability to quickly prevent further blood clots and the expansion of existing clots and thus limit the amount of damage to the heart's muscle.

Aspirin is easy to use, safe at the low doses used for its antiplatelet action, and fast acting. Aspirin at moderate doses (160-325 mg/day) produces an antiplatelet effect rapidly (within 30 minutes). The current recommendation is to give aspirin immediately to almost all patients as soon as a heart attack is recognized at a dose of 160-325 mg/d and to continue it for one month. The only reason for not using aspirin is a history of intolerance or allergy to aspirin or evidence obvious active bleeding (such as actively bleeding stomach ulcers).

Performance of vascular procedures

Aspirin is not the only treatment for heart attacks and unstable angina. Sometimes percutaneous transluminal coronary artery angioplasty (PTCA), with or without placement of an arterial stent, is necessary to open narrowed or blocked coronary arteries. In rare instances, PTCA may be technically impossible, or not practical, to do, and coronary artery bypass graft surgery (CABG) becomes necessary to improve the flow of blood to the heart.

Some patients with heart attacks are treated with thrombolytic agents (medications that dissolve clots) to open blocked arteries. It is important to make the distinction that aspirin generally does not open an existing blood clot, but it acts to prevent propagation of the existing clot and the formation of new ones. In all of these instances, there is a risk that blood clots will form again inside the arteries, leading to further heart attacks. In all of these cases, aspirin has been shown to be beneficial in preventing new clots, thus reducing the risk of heart attacks and improving both short and long-term survival.

Prevention of further heart attacks

There are two types of heart attack prevention, primary and secondary. Preventing the first heart attack is called primary prevention. Preventing further heart attacks among patients who already have had a heart attack is called secondary prevention.

Within six years after the first heart attack, 16% of men and 35% of women will have a second heart attack. Long-term, daily aspirin (75-325 mg/d) has been shown to reduce the risk of second heart attacks and improve survival among both men and women. Additionally, long-term secondary prevention with aspirin also has resulted in fewer ischemic (lack of blood flow due to blockage in blood vessels from clot formation) strokes. Therefore, survivors of heart attacks usually take daily low dose (75 mg-160 mg/d) aspirin indefinitely to prevent further heart attacks as well as strokes.

Aspirin taken long-term is an important part but NOT the only measure for preventing heart attacks.

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.

What is the optimal dose of aspirin for treating and preventing heart attacks and strokes?

An ideal dose of aspirin is one that maximizes its benefits but minimizes side effects. However, the ideal dose of aspirin for primary or secondary prevention of ischemic strokes and heart attacks has not been established firmly.

In situations where an immediate antiplatelet effect is needed (for example, in the treatment of acute heart attacks, ischemic strokes, and unstable angina) aspirin at moderate doses (160–325 mg/day) will produce rapid and immediate antiplatelet effects. In the ISIS-2 trial, a dose of 160 mg/day given within 24 hours of the onset of symptoms of heart attack was shown to decrease deaths due to heart attacks by 23%. Therefore, this is the dose recommended for acute heart attacks and unstable angina.

At lower doses, such as 75 mg/d, the antiplatelet effect of aspirin can be achieved in several days instead of minutes. Since the risk of serious bleeding from aspirin is lower at lower doses, 75 mg/d is an appropriate dose for long-term primary and secondary prevention. Even though aspirin at doses as low as 40 mg/d has been shown to have anti-platelet effects, there is insufficient and inconclusive data to show that such low doses are effective in preventing heart attacks and ischemic strokes.

There also is no evidence that higher doses of aspirin, such as 1000 mg/day or higher, is more effective than lower doses. Some studies even suggest that higher doses may not be as effective as lower doses. Since the side effects of aspirin are more frequent with higher doses, doctors generally do not recommend higher doses for long-term use.

The USPSTF also looked into the optimal dose of aspirin for primary preventive purposes in 2009. They concluded that the low doses of 75-100mg daily were as effective as higher doses in preventing vascular disease and less associated with bleeding complications.

Who should be taking aspirin to prevent heart attacks and strokes?

Even though aspirin is available without a doctor's prescription and has been used safely for many years by patients for fever and pain, patients should NOT take aspirin on a long-term basis without consulting with their doctor.

Aspirin prevents blood clots from forming inside arteries affected by atherosclerosis, but aspirin does not prevent atherosclerosis. Other measures (losing excess weight, controlling high blood pressure and diabetes, lowering LDL cholesterol, increasing HDL cholesterol, and stopping cigarette smoking) are necessary to prevent atherosclerosis.

Most doctors now recommend low doses of aspirin long-term for patients with advanced atherosclerosis for secondary prevention purposes. Such patients include those with:

• prior heart attacks
  
  
• prior strokes
  
  
• exertional and unstable angina
  
  
• TIAs (transient ischemic attack, mini-stroke)
  
  
• peripheral vascular disease (poor artery blood flow to the legs)
  
  
• vascular procedures such as PTCA and CABG

Doctors also consider low dose aspirin in patients at risk for atherosclerosis because they:

• Have high blood LDL cholesterol
  
  
• Are males over 45 or are postmenopausal or over 55 females
  
  
• Have high blood pressure (hypertension) after high blood pressure is controlled with medications
  
  
• Use tobacco
  
  
• Have diabetes mellitus
  
  
• Have a family history of coronary heart disease

Who should not be taking aspirin?

Patients who should not be taking aspirin include:

• Patients with an allergy to aspirin or other NSAIDs;
  
  
• Patients with active ulcers, especially those with bleeding ulcers, because of the side effects of ulcers and bleeding with aspirin. Among patients who must take aspirin but have had intestinal ulcers, the lowest does of aspirin should be used only after the ulcers heal. It should also be taken together with a proton pump inhibitor such as pantoprazole (Protonix), esomeprazole (Nexium), rabeprazole (Aciphex), or lansoprazole (Prevacid, Prevacid SoluTab) to decrease the risk of recurrent ulcers;
  
  
• Pregnant women and nursing mothers (since aspirin is excreted into breast milk);
  
  
• Teenagers and children with the flu or chickenpox because of the associated risk of Reye's syndrome, a serious disease of the liver and nervous system that can lead to coma and death;
  
  
• Patients with advanced kidney or liver diseases since aspirin may cause toxicity to the kidney and liver;
  
  
• Patients at risk for developing intracranial hemorrhage;
  
  
• Some patients undergoing elective surgery or procedures (Patients taking aspirin should discuss with their doctors whether to stop aspirin for several days to up to two weeks before surgery and procedures to avoid excess bleeding.)

What are the side effects of aspirin?

Serious side effects of aspirin and other NSAIDs occur infrequently. However, they may occur and generally tend to be more frequent with higher doses. Therefore, it is advisable to use the lowest effective dose to minimize side effects.

The most common side effects of aspirin involve the gastrointestinal system.

Aspirin can cause:

• ulcers of the stomach and duodenum (first part of the small intestine),
  
  
• abdominal pain,
  
  
• nausea,
  
  
• gastritis (inflammation of the stomach), and
  
  
• even serious gastrointestinal bleeding from ulcers.

Occasionally, aspirin may be toxic to the liver.

Sometimes, ulcers of the stomach and bleeding occur without any abdominal pain, and the only signs of bleeding may be:

• black tarry stools,
  
  
• weakness, and
  
  
• dizziness upon standing (orthostatic hypotension).

Another serious but rare side effect of aspirin is intracranial hemorrhage (bleeding into the tissues of the brain), similar to a hemorrhagic stroke.

Aspirin can impair function of the kidney and liver, especially in patients who already have liver and kidney disease. Other side effects of aspirin include easy bruising, vertigo, ringing in the ears (tinnitus), and lightheadedness.

Serious side effects of aspirin, such as bleeding ulcers or intracranial bleeding, are rare (less than 1% of patients) among patients taking moderate doses of aspirin (for example, 325 mg/d). Serious side effects of aspirin should be even lower with low doses such as 75-160 mg/d. However, the actual incidence of serious bleeding with long-term use of low dose aspirin has not been clearly determined.

What is aspirin allergy?

Allergy to aspirin is a rare condition in which a patient can develop swelling of tissues, spasm of the airways (bronchospasm) that causes difficulty breathing, and even anaphylaxis, a life-threatening condition. Clearly, patients with a history of allergy to aspirin should not take aspirin. Since aspirin is related chemically to the other NSAIDs, patients who are allergic to the other NSAIDs, such as ibuprofen (Motrin) and naproxen (Aleve), also should not take aspirin.

What interactions might aspirin have with other medications?

Aspirin may interact with other medications and cause undesirable side effects. For example:

• Aspirin, when taken together with an anti-coagulant such as warfarin (Coumadin) or enoxaparin (Lovenox), can greatly impair the body's ability to form blood clots, resulting in excessive bleeding spontaneously, from ulcers, or related to a procedure. Therefore, patients on such combinations must be closely monitored by a doctor.
  
  
• Aspirin can raise levels of uric acid in the blood and may need to be avoided in patients with increased uric acid levels or gout.
  
  
• Aspirin can increase the effect of medications used for lowering blood sugar levels in patients with diabetes, resulting in abnormally low blood sugar levels (hypoglycemia). Blood sugar levels may need to be more closely monitored.
  
  
• Certain NSAIDs, particularly ibuprofen (Motrin, Advil), if taken just before aspirin or in multiples doses each day, can reduce the anti-platelet effects of aspirin and theoretically render aspirin less effective in preventing heart attacks and ischemic strokes. The ibuprofen molecule is believed to adhere to the COX-1 enzyme, thus keeping aspirin from reaching the enzyme.

What can be done to reduce the risk of ulcers from long-term aspirin use?

Long-term low dose aspirin use is generally safe. An estimated 10% of the patients taking long-term aspirin (75-325 mg/day) can develop ulcers. Most of these ulcers were asymptomatic (no abdominal pain or bleeding). Patients at a higher risk of developing ulcers with low dose aspirin included elderly patients age 70 years and older, and patients with H. pylori stomach infection (see below). The risk of significant ulcer bleeding from aspirin is low (approximately 1%). One can reduce the risk of bleeding by adding a daily dose of a proton pump inhibitor for example, pantoprazole (Protonix), esomeprazole (Nexium), rabeprazole (Aciphex), or lansoprazole (Prevacid, Prevacid SoluTab), and omeprazole (Prilosec, Zegerid).

Chronic H. Pylori infection of the stomach is found in up to 30% of adults in the U.S. Patients with gastritis due to H. pylori will have a higher risk of bleeding when given aspirin or NSAIDs long-term. Eradication of H. pylori from the stomach with antibiotics can reduce the risk of bleeding from chronic aspirin use.

Buffered and coated aspirin do not seem to have any beneficial effect in preventing ulcers and ulcer bleeding.

What are the limitations of aspirin treatment?

Aspirin is not always effective in preventing strokes and heart attacks. Examples of possible causes of aspirin failure include:

• Poor patient compliance (not taking the medication regularly)
  
  
• Inadequate dosing
  
  
• Concurrent intake of other NSAIDs such as ibuprofen that interferes with the anti-platelet action of aspirin
  
  
• Activation of platelet aggregation via pathways not blocked by aspirin
  
  
• Aspirin resistance

What is aspirin resistance?

Aspirin resistance can be defined as the lack of antiplatelet effect despite therapeutic doses of aspirin (75mg-150mg/day for at least five days). This lack of anti-platelet response to aspirin increases the risk of developing heart attacks, strokes, and related deaths. Aspirin resistance is different from other causes of aspirin failure (see above), such as patient non-compliance or drug interference from concomitant use of ibuprofen.

Some scientists believe that a segment of the population is resistant to the antiplatelet effect of aspirin. In these aspirin-resistant individuals, aspirin does not inhibit the formation of thromboxane A-2. Resistant individuals can be identified in research settings by finding high levels of 11-dehydrothromboxane B2 (a metabolic breakdown product of thromboxane A-2) in the urine while taking aspirin. These individuals have a higher risk of heart attack and strokes than subjects with lower urine levels of 11-dehydrothromboxane B2.

Another way of identifying aspirin resistance in research settings is by optical platelet aggregation. Aspirin nonresponders identified by this method were found to have higher rates of heart attacks, strokes, and death than aspirin responders.

What is in the future for the research on aspirin resistance?

While research scientists are increasingly convinced that aspirin resistance exists, there are no reliable and standardized tests that doctors in clinical practice can use to diagnose this condition. Large scale controlled studies are needed to validate and standardize laboratory tests of aspirin resistance, and link these tests results to clinical outcomes.

Clinical trials will also be needed to determine how best to treat aspirin resistance. For example, should patients diagnosed as having aspirin resistance be treated with higher doses of aspirin? Should they be treated with aspirin in combination with another anti-platelet agent? Or should they be treated with a different anti-platelet agent, such as clopidogrel bisulfate (Plavix)?

References:
U.S. Preventive Services Task Force; "Aspirin for the Prevention of Cardiovascular Disease: U.S. Preventive Services Task Force Recommendation Statement;" Annals of Internal Medicine; 17 March 2009. Volume 150 Issue 6. Pages 396-404.
ISIS-2 (Second International Study of Infarct Survival) Collaborative Group (1988), "Randomized Trial of Intravenous Streptokinase, Oral Aspirin, Both, or Neither Among 17 187 Cases of Suspected Acute Myocardial Infarction: ISIS-2", The Lancet 332: 349-360
Cairns JA, Gent M, Singer J, Finnie KJ, Froggatt GM, Holder DA, Jablonsky G, Kostuk WJ, Melendez LJ, Myers MG, et al.; "Aspirin, sulfinpyrazone, or both in unstable angina. Results of a Canadian multicenter trial." N Engl J Med. 1985 Nov 28;313(22):1369-75.
Theroux P; Ouimet H; McCans J; Latour JG; Joly P; Levy G; Pelletier E; Juneau M; Stasiak J; deGuise P; et al. "Aspirin, heparin, or both to treat acute unstable angina." Journal of Medicine Vol. 319:1105-1111
LC Wallentin; "Aspirin (75 mg/day) after an episode of unstable coronary artery disease: long-term effects on the risk for myocardial infarction, occurrence of severe angina and the need for revascularization. Research Group on Instability in Coronary Artery Disease in Southeast Sweden"J Am Coll Cardiol, 1991; 18:1587-1593
C. H. Hennekens, MD; M. L. Dyken, MD; V. Fuster, MD. "Aspirin as a Therapeutic Agent in Cardiovascular Disease;" Circulation. 1997;96:2751-2753