Drugs for Initial Treatment of Ischemic Stroke
Intravenous Thrombolytics. Clot-busting, or thrombolytic, drugs, normally used for breaking up existing clots in people who have had heart attacks, are now administered intravenously for ischemic (not hemorrhagic) stroke. The standard thrombolytic drug used for stroke is t-PA or alteplase (Activase). Streptokinase is also sometimes used and others are under investigation. The following steps are critical before administering these agents.

 
• Before t-PA is given, a CT scan must also first confirm that the Stroke  is not hemorrhagic.  
• Thrombolytics must be administered within three hours of a stroke (but not after that period) to have any effect. Unfortunately, most stroke patients arrive at the hospital more than three hours after an attack and therefore are not eligible for treatment. This delay is the primary reason why only 1% to 2% of stroke patients are receiving these agents.

T-PA itself carries a risk for hemorrhage and they may not be appropriate for patients with existing risk factors for bleeding. The drug may be appropriate in more patients than previously thought, however, including older people, those with a history of stroke, and those with high blood pressure. More research is needed to confirm this. Thrombolytics are used less frequently than they should be in certain groups, particularly African Americans.

Intra-Arterial t-PA . Researchers are investigating a t-PA agents injected directly into an artery in the brain. Early studies suggest this approach may allow effective treatment up to six hours after a stroke and improve recovery in more patients. The risk for bleeding is increased, however.

Ancrod. Ancrod is an agent derived from the venom of a pit viper snake that reduces the amount of a blood clotting factor called fibrinogen. Although it is not actually a clot-busting drug, some experts believe it might be a possible alternative to thrombolytics. Studies are reporting less disability in patients who are given ancrod within three hours of the stroke. (It is not clear yet whether the agent improves survival.) As with all anti-clotting agents, there is a slightly higher risk for hemorrhage.

Anti-Clotting Medications
Medications that prevent blood from coagulating or clotting have been used for years in people at risk for a recurring stroke. They may also be warranted in some patients at high-risk for a first stroke. A major analysis of 17 trials reported that in patients with a history of TIA or stroke antiplatelet treatment reduced the chances of a second stroke, heart attack, and related deaths by 22%. These benefits were evident in men and women of any age, including those with and without hypertension or diabetes. In general, they are initiated within 48 hours of an ischemic stroke and continued as maintenance.

The specific anti-clotting agents are generally recommended in the following order:

Aspirin. A 2000 review of four trials found no evidence that aspirin can prevent a first ischemic stroke (although the studies reviewed in the report had been conducted using subjects at risk for heart disease, not stroke.) Aspirin has some modest effect in preventing a second stroke and is the most widely recommended agent as initial therapy in doses of between 50 and 325 mg. It is not clear if aspirin should be used after a first stroke in patients who have been taking it before the stroke for heart attack prevention or other medical problems.

Aggrenox. Aggrenox is the brand name for a single capsule containing both low-dose aspirin and extended release dipyridamole, an anti-platelet agent. The two agents have complementary actions and are somewhat more effective than ordinary aspirin for preventing a second stroke in high-risk people; the drug also has a good safety profile. Aggrenox is much more expensive than aspirin, however, and is usually recommended only if aspirin does not appear to be helpful.

Thienopyridines. Ticlopidine (Ticlid) or clopidogrel (Plavix) are anti-blood platelet agents known as thienopyridines. They are slightly more protective against stroke than aspirin, but they are costly. Typically, they are options for patients who cannot tolerate or who do not respond to aspirin. These agents however, can have severe side effects. Ticlopidine particularly has been associated with reversible lupus-like symptoms (an autoimmune disease), reversible neutropenia (a drop in white blood cells), and thrombocytopenia (a severe drop in platelet counts). Clopidogrel has been preferred because of its better safety record, but reports of thrombocytopenia in patients taking clopidogrel have created concern.

Warfarin. The anticoagulant warfarin (Coumadin) is a potent anti-clotting agent and needs to be monitored carefully, as it can lead to bleeding. An important study in 2001 suggested, however, that it is no more effective than aspirin in preventing a second stroke. Warfarin may still be useful in certain patients, such as those with atrial fibrillation or high-risk patients who do not respond to other anti-platelet drugs.

All anti-clotting drugs carry a risk for bleeding. Of some concern in this regard are studies reporting a higher than usual risk for Hemorrhagic stroke with long-term use of aspirin. Any risk for Hemorrhagic stroke is still very low, particularly with low-dose aspirin.

Drugs for Hemorrhagic Stroke
Calcium Channel Blockers. One of the most common and serious dangers after a subarachnoid Hemorrhagic stroke is spasm of the blood vessels near the ruptured site, which closes off oxygen to the brain. Calcium causes contraction of the smooth muscles of the blood vessels, and calcium channel blockers are drugs that relax the blood vessels. One, nimodipine (Nimotop), has been tested in a number of trials with considerable success. The drug works best if it is administered within six hours of the stroke. Calcium channel blockers are not useful for ischemic stroke.

Urokinase Irrigation. Introducing irrigation tubes and administering urokinase (a thrombolytic agent) after surgically removing an aneurysm may help prevent spasm.

Investigative Drugs Used to Protect or Restore Nerve Cells after a Stroke
Nerve-Protecting Agents. Researchers are currently working to develop medications that may slow down or prevent the cascading process that destroys nerve cells after a stroke. Many investigative drugs are targeting the excitatory amino acids, such as glycine and glutamate, which are known to destroy nerve cells after a stroke.

Studies to date have been discouraging. Of note, gavestinal, an investigative agent that blocks glycine, produced no significant benefits for stroke patients in two major trials. Other nerve-protecting agents being investigated that have shown some promise include citicoline, clomethiazole, piracetam, and ebselen.

Agents for Nerve Regeneration. It has been thought that when cells in the brain were destroyed, new ones could not grow to replace them. Scientists have now observed, however, that nerve regrowth (neurogenesis) can occur in the adult human brain. This exciting discovery opens the way for new agents that might in the future stimulate nerve growth and repair damage done by many neurologic diseases, including stroke.

One investigative technique involves the transplanting of laboratory-grown nerve cells into the brains of stroke patients in order to improve motor and speech skills. Six of twelve people who had had strokes in years (rather than days) past, and who received such cells appear to improve their motor skills, but the 2000 study was far too small to be definitive.