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Therapy for ischemic stroke is usually delivered in three phases based on the amount of time since the stroke occurred. First, clot-busting drugs are administered to dissolve a blood clot blocking the artery. These are followed by anticoagulant drugs to prevent new blood clots from forming. The third phase consists of preventive medications aimed at avoiding another stroke. This course of three-phase treatment is also used for a TIA.

Phase 1: Early, hyperacute phase

This period spans the first minutes to several hours after stroke symptoms begin. As soon as an ischemic stroke or TIA is diagnosed, the first goal is to determine whether a clot is still blocking an artery and to consider whether to give medication to dissolve the clot.

Thrombolytic therapy

You may be given a clot-dissolving drug (thrombolytic therapy) to dissolve the blockage and restore blood flow to the brain. Drugs of this type, frequently used to treat heart attacks, have been found useful in treating ischemic stroke as well. But they carry the risk of causing a hemorrhage, so doctors must carefully consider whether to use them.

The drug will be given either intravenously through a thin tube in your arm or intra-arterially through a catheter threaded through your blood vessels directly to the site of the blockage.

Intravenous. The drug given for intravenous thrombolytic therapy is recombinant tissue plasminogen activator (tPA), one of the first genetically engineered medications. Intravenous tPA was developed to dissolve small clots by generating the enzyme plasmin, which digests the strands of fibrin that form clots (see Figure 13). When tPA works, its benefit is long term. A study sponsored by the National Institutes of Health showed that although people treated with tPA did not show any improvement after just one month, there was some improvement after three months.

This drug is best given within three hours of the onset of stroke because it can lead to a hemorrhage in the brain if given later. The more time that passes between stroke onset and the administration of tPA, the greater the risk of hemorrhage.

Intra-arterial. This is a different method for delivering clot-busting (thrombolytic) medication, using a catheter placed in the artery near the clot. Either of two drugs can be used — tPA or an older, similar drug called urokinase (Abbokinase). Doctors consider this approach when a major artery appears to be blocked. This method is particularly effective because, in addition to releasing medicine to help dissolve the clot, the doctor can use the tip of the catheter to dislodge it. One study demonstrated its effectiveness when it was used to remove a clot in the major arteries at the base of the brain. This treatment can be used only in the first few hours after a stroke because of the risk of hemorrhage, but in some cases it results in a dramatic recovery within hours. It is best done by a skilled team headed by a stroke neurologist. People who suffer a stroke in the brainstem area have been shown to benefit from this treatment up to six hours after the attack.

Medication to prevent further clots from forming (antithrombotic, or anticoagulant, therapy such as heparin) may also be useful at this stage (see Table 1). It is sometimes given either as an alternative to thrombolytic therapy or after the effect of thrombolytic therapy has worn off.

Download PDF: Medications commonly used for ischemic stroke

Phase 2: Acute and subacute phase

The acute and subacute phase therapy will begin after the thrombolytic treatment has ended, or if your doctors decide not to use thrombolytic treatment. Phase 2 therapy can last several days, until you receive a confirmed, precise clinical diagnosis and begin therapy to prevent another stroke.

During phase 2, MRI images of your brain may be taken to look for further damage from the stroke. If you did not seek medical help during the hyperacute phase, doctors will go directly to acute phase therapy and try to determine whether an artery is blocked and, if so, where and why. Intravenous antithrombotic, or anticoagulant, medication is often used during phase 2 therapy to prevent further clotting. If you've had an embolic stroke, you may also undergo echocardiography, heart monitoring, and various laboratory tests. These can help the doctor predict your risk of developing a blood clot in the heart.

Thrombolytic medication is not an option during phase 2 therapy because of the risk of hemorrhage. An area of the brain already damaged by a stroke can hemorrhage drastically beyond the area already affected by the clot.

Antithrombotic (anticoagulant) therapy

Antithrombotic drugs (also known as anticoagulants or blood thinners) help prevent the formation of blood clots. In the acute phase, doctors typically use heparin — delivered intravenously or by injection — for this purpose. Oral anticoagulant therapy, such as warfarin (Coumadin), may be used later, in the preventive phase.

Doctors consider using intravenous heparin when clot-dissolving (thrombolytic) therapy is not given or, in selected cases, immediately after intra-arterial thrombolysis in order to keep the blood vessel open. Intravenous heparin is most often used in treating stroke or TIA caused by a narrowing in a major artery, such as the carotid artery, the middle cerebral artery, the distal vertebral artery, or the basilar artery, where further clotting and embolization are likely to occur.

Doctors also consider using this drug to treat embolic stroke if thrombolytic therapy is not given, particularly when the embolic clot is thought to still be in the brain artery before it dissolves naturally. Because there hasn't been a large clinical study of heparin in which the precise cause of the stroke or TIA was documented, proof of its effectiveness is lacking. Therefore, doctors must evaluate each situation on a case-by-case basis. It may be useful when the cause of stroke or TIA is a clot blocking a major artery in the neck or at the base of the brain that could expand and cause more damage, although some physicians are not convinced that it helps.

Phase 3: Secondary prevention of stroke

The third phase, known as secondary stroke prevention, begins a day or more after the stroke or TIA occurs, once doctors have fully evaluated the condition of the artery involved and confirmed the exact cause. This treatment phase continues indefinitely after you go home. The goal is to prevent a second stroke from the same problem that caused the first. Secondary stroke prevention therapy can involve medications to help prevent future blood clots (oral anticoagulant therapy or antiplatelet therapy), blood pressure medicine, or surgery. In virtually all people, the underlying causes of the stroke — including high blood pressure, high blood cholesterol, and diabetes — must also be treated during phase 3. Other recommendations for people who have had an ischemic stroke or TIA is to reduce modifiable risk factors, such as quitting smoking and increasing physical activity (see "Preventing stroke").

If you have had an ischemic stroke or TIA, you may receive some of the following therapies. Doctors may also search for clotting abnormalities in the heart and blood vessels, as well as for a deficiency of vitamin metabolism, which may suggest further preventive therapies for embolic or large-artery atherothrombotic stroke.

Oral anticoagulant therapy

The oral anticoagulant warfarin is the treatment of choice for stroke patients with atrial fibrillation or certain other cardiac conditions, such as prosthetic heart valves or cardiac thrombus after a heart attack.

For many other people, however, there is no clear benefit for warfarin over aspirin, an antiplatelet medication (see "Antiplatelet therapy"). A large study in the New England Journal of Medicine in 2001 found no significant difference between the two medicines for most stroke patients. (The study excluded people with atrial fibrillation and some other cardiac conditions because of warfarin's demonstrated advantage for them. People with severely narrowed arteries were not studied because some doctors think that warfarin is beneficial for them, or the patients were on antiplatelet therapy when they had the first stroke.) Further studies are under way to clarify which stroke patients benefit from warfarin.

Most doctors now think that the decision to use warfarin or aspirin should be made on an individual basis. The advantages of aspirin are that it is inexpensive and readily available. Its chief disadvantage is that it can cause gastrointestinal side effects, such as bleeding. The downside of warfarin is that you need to have regular blood tests (see "Keeping track of clotting") to make sure your blood's clotting ability is at an acceptable level and prevent hemorrhage.

Antiplatelet therapy

Platelets are disc-shaped cells in blood that clump together to start the process of clot formation. Platelets are essential for wound healing because they form the clots that staunch blood flow in a wound. Too much platelet activity can be dangerous because it can lead to a stroke. Antiplatelet therapy is designed to keep platelets from forming dangerous clots. It currently includes three medications: aspirin, clopidogrel (Plavix), and Aggrenox (aspirin with dipyridamole). A fourth medication, ticlopidine (Ticlid), is not used any longer because it is more expensive and has been associated with gastrointestinal disturbances, diarrhea, rash, and problems with the production of blood products in the bone marrow.

Aspirin. Aspirin is generally reserved for people who have had small-vessel strokes and people with embolic strokes or large-artery strokes in which warfarin's efficacy is uncertain. Many doctors also give aspirin to people with embolic stroke after they have finished their course of warfarin therapy, which generally lasts for six months. A significant limitation of aspirin is that it can cause gastrointestinal discomfort and bleeding.

Clopidogrel. Clopidogrel (Plavix) has fewer gastrointestinal side effects than aspirin, but it is more expensive. Doctors typically prescribe clopidogrel for people who can't tolerate aspirin.

Aggrenox. This is a combination of aspirin and dipyridamole, another antiplatelet agent. Its effectiveness in preventing stroke and TIA, as well as its likelihood to cause side effects, is similar to that of aspirin or clopidogrel alone but because it contains a lower dose of aspirin, it may be better tolerated in patients who are sensitive to aspirin.

Antihypertensive medications

Lowering blood pressure with antihypertensive medications reduces the risk of recurrent stroke in people who have had an ischemic stroke or a TIA, even in those without high blood pressure. Therefore, in its guidelines for preventing recurrent strokes, the American Stroke Association (a division of the American Heart Association) recommends high blood pressure treatment for anyone recovering from an ischemic stroke or a TIA. Research has found that a combination of diuretics and ACE inhibitors is beneficial for secondary stroke prevention, but the guidelines state that the choice of drug should be made on an individual basis. Lifestyle modifications that reduce blood pressure are also recommended, such as quitting smoking, losing weight, moderating alcohol consumption, and exercising (see "Lower your blood pressure"). A blood pressure reduction of an average of 10/5 mm Hg can lower the risk of another stroke, although the optimal amount of blood pressure reduction is unclear.

Carotid endarterectomy

The carotid arteries are the two arteries on either side of the neck that channel blood to the brain. A stroke occurs when one of them is blocked, so surgery to remove the obstruction reduces the likelihood of a recurrence. This surgical procedure, called carotid endarterectomy, is often the best treatment after a TIA or minor ischemic stroke that results from a significant narrowing (at least 70%) of a carotid artery, and it may also be appropriate for some people with less complete obstruction. If you are a candidate for carotid endarterectomy, you and your doctor must weigh the complex risks, which include the chance of a heart attack or even a stroke, against the potential benefits of the procedure in your case.

Before having a carotid endarterectomy, you'll probably have an ultrasound imaging study of your brain and its arterial supply to give your surgeon a road map of the narrowed blood vessels. Doctors rarely recommend using cerebral angiography for this purpose because this invasive procedure has some risk. Noninvasive arterial flow analysis and imaging techniques such as transcranial Doppler ultrasound, carotid duplex ultrasound, CTA, and MRI are used to identify the site of blockage, determine how much it is narrowing a blood vessel, and whether it alters blood flow to the brain (see "Imaging and blood-flow studies"). Transcranial Doppler can also assess the location and adequacy of collateral blood flow coming around the Circle of Willis to take over from the narrowed carotid artery.

Carotid endarterectomy is a major surgical procedure that usually requires one or two days in the hospital. You will probably be given general anesthesia, although under some circumstances, it may be local anesthesia. The surgeon makes an incision in the neck and opens the blocked carotid artery. After removing the plaque and cleaning out the artery, the surgeon stitches the artery back together and closes the incision (see Figure 14).

During your hospital stay, your blood pressure will be carefully monitored and controlled. Even after you leave the hospital, your neck will feel sore and you'll have trouble swallowing for a few days. You won't be allowed to do any heavy lifting for three weeks, but you should be able to return to your normal daily activities within a month.

In general, carotid endarterectomy is performed on people who have had a TIA or a small stroke that suggests a major stroke could be imminent. Studies suggest, however, that certain high-risk but otherwise healthy individuals who have not had a TIA or small stroke may also benefit from the procedure, particularly if the narrowing in the internal carotid artery is severe enough to cause a blood pressure drop in the artery. Doctors can identify such people by using a combination of carotid duplex Doppler and transcranial Doppler ultrasound to study blood flow in the carotid and brain arteries. If you are advised to undergo a carotid endarterectomy, a second opinion can be helpful. Physicians and surgeons with extensive experience and a good understanding of cerebral circulation and the medical risks of surgery make the best team.

Doctors sometimes perform an emergency carotid endarterectomy in the early, acute stage of an ischemic stroke, but only in special circumstances. Many experts agree, however, that the procedure is safe when performed on a nonemergency basis after evaluating medical risk, especially cardiac risk. Carotid endarterectomy may be able to prevent a larger, more catastrophic stroke in people who have had a small atherothrombotic stroke. Patients who have suffered a large, more complete stroke usually don't benefit from this type of emergency surgery; in fact, it can be dangerous for them.

Carotid artery stenting

As in the treatment of coronary artery disease, a stent can be used to prop open a carotid artery that has been severely narrowed by atherosclerotic plaque. A stent is a prosthetic device inserted into the artery to keep it from closing up and causing a stroke. A carotid artery stent is applied by a wire inserted into the aorta and then threaded to the carotid artery. The stent is left there to widen the diameter of the vessel.

The stent's job is to prevent stroke from low blood flow or artery-to-artery embolus. A stent is most often used to treat a narrowing at the origin of the internal carotid artery. But studies have not yet shown whether this procedure is safe and effective enough to replace carotid endarterectomy. Studies are under way to examine these issues.

Carotid artery stenting is usually considered when someone is a candidate for carotid endarterectomy but is too frail to undergo major surgery. Stenting is sometimes considered a "last chance" treatment of very severe narrowings of the large intracranial arteries. Even in these circumstances, the benefit and safety of carotid artery stenting have not been proved. The procedure is best done only at a hospital with an experienced stroke team.

Source: from Harvard Health Publications, Copyright © 2008 Harvard University. All rights reserved. Harvard Medical School does not endorse products.
Used with permission of StayWell.
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