Stroke

Description

Alternative Names

Medications

An intriguing study in 2003 suggested that taking a single daily pill containing a number of heart- and circulatory protective agents could largely prevent heart attacks and stroke in nearly everyone over 55. It would contain the following:

• A statin (such as Lipitor or Zocor). Statins inhibit the liver enzyme HMG-CoA reductase, which is used in the manufacturing of cholesterol. They are the most effective drugs for the treatment of high cholesterol, and, according to a 2003 major analysis over 200 studies, they reduce risk for heart events by 60% and stroke by 17%. In addition, statins may have nerve-protecting properties that may help stroke sufferers.
• Three blood-pressure lowering agents in low doses (e.g., a thiazide diuretic, a beta blocker, and an ACE inhibitor). An important study in 2003 suggested that using low-doses of three different agents to lower pressure may reduce the risk of stroke by 63% and heart disease by half. Using low doses also reduces the risk for side effects.
• Aspirin (low-dose).
• Folic acid. Folic acid lowers levels of homocysteine, an amino acid believed to increase the risk for heart disease and stroke.

The experts in the study believed this combination would reduce ischemic heart events by 88% and stroke by 80%. Only between 1% and 2% of the population would have to withdraw because of side effects. More research on this is certainly warranted.

Thrombolytics and Other Drugs for Initial Treatment of Ischemic Stroke

Intravenous Thrombolytics. Clot-busting, or thrombolytic, drugs break up existing blood clots. They are among the important treatments for heart attacks, and are now also being used for ischemic (not hemorrhagic) stroke. Their benefits for treating stroke patients appear to be more limited than for heart attacks, however, and only a minority of stroke patients is given these agents. More needs to be learned about the risks and benefits of thrombolytics for stroke.

The standard thrombolytic drugs are recombinant tissue plasminogen activators or rt-PAs. They include alteplase (Activase and reteplase (Retavase)). Both are similar in effectiveness, although reteplase is easier to administer. Others are under investigation.

The following steps are critical before administering these agents.

• Before the thrombolytic is given, a CT scan must also first confirm that the stroke is not hemorrhagic. If the stroke is ischemic, a CT scan can also suggest if injuries are very extensive, which might affect the use of thrombolytics.
• 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.

Thrombolytics carry a risk for hemorrhage and so may not be warranted for patients with existing risk factors for bleeding. They should not be used in patients who are experiencing seizures. 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.

Intra-Arterial Thrombolytics. Researchers are investigating thrombolytics 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 and hemorrhagic stroke is significantly increased, however.

Fibrin-Depleting Agents.These drugs deplete the amount of fibrinogen in blood, which in turn reduces the "stickiness" in blood. Such agents include ancrod and batroxobin (Defibrase), which are derived from the venom of poisonous snakes. Some experts believe these agents might be a possible alternative to thrombolytics. Studies suggest they may modestly reduce the risks for death and disability if given early on. As with all anti-clotting agents, there is a higher risk for hemorrhage, but it appears to be slight.

Anti-Clotting Medications for Preventing a Recurring Stroke

Medications that prevent blood from coagulating or clotting are used to prevent a recurring or second stroke. They are generally either anti-platelet agents or anticoagulants. Specific anti-clotting agents may be warranted depending on risk factors.

Anti-Platelet Agents.Typically, an anti-platelet agent--most often aspirin--is initiated within 48 hours of an ischemic stroke and continued in low doses as maintenance. Studies suggest that antiplatelet therapy can reduce the risk for a second stroke by 25%.

• Aspirin. Aspirin has some modest effect in preventing a second stroke and is recommended within 48 hours of a first stroke in doses of between 50 and 325 mg. Note, patients should not be given an aspirin until a diagnosis of ischemic or hemorrhagic stroke has been determined. Aspirin increases the risk for bleeding in patients with hemorrhagic stroke and taking it would preclude important clot-busting drugs in appropriate patients with ischemic stroke. On an ongoing basis, experts now recommend that most patients take a daily low-dose aspirin to prevent a second stroke. If patients had already taking aspirin for preventing heart disease, it is not clear it they should take if after a first stroke.
• Thienopyridines. Clopidogrel (Plavix) and ticlopidine (Ticlid) are anti-blood platelet agents known as thienopyridines. (Clopidogrel is preferred over ticlopidine because of its better safety record.) Evidence strongly suggests that clopidogrel is more protective against stroke than aspirin and appears to be as safe. It is more expensive, however. Typically, it is an option for patients who cannot tolerate or who do not respond to aspirin.
• Glycoprotein IIB/IIIa Inhibitors. Glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors are potent drugs that reduce clotting by blocking platelets (clotting factors in the blood). They are administered intravenously in the hospital and include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), tirofiban (Aggrastat), lortrafiban, and lamifiban. They are being investigated along or as add-on agents to thrombolytic drugs.

Anticoagulants.Anticoagulants thin blood and may be useful under certain circumstances.

• Warfarin. The anticoagulant warfarin (Coumadin) is a potent anticoagulant and needs to be monitored carefully. Studies have been mixed on its value for protecting against future stroke. A 2001 study found no additional benefits for patients with ischemic stroke compared to aspirin. Warfarin is, however, very important in high-risk patients with atrial fibrillation. It may be useful in other situations, such as patients with patent foramen ovale (PFO), those whose stroke followed a heart attack, or in high-risk patients who do not respond to or cannot take other anti-platelet drugs.
• Heparin. Intravenous heparin, a potent anti-platelet agent, has been used for ischemic stroke since 1941. Although many physicians continue to use it, five out of six major studies have reported no clear protective benefits compared to aspirin with the use of standard heparin or any heparin-like agents. They also pose a much higher risk for hemorrhagic stroke. Experts now recommend heparins only for preventing thromboembolism in stroke patients at risk for this condition.
• Direct Thrombin Inhibitors (DTIs). Direct thrombin inhibitors are a more recent group of anti-coagulants. The first DTI hirudin, a natural substance derived from the saliva of leeches. New forms include argatroban (Novastan), bivalirudin (Angiomax), danaproid (Orgaran), lepirudin (Refludan), desirudin (Revasc), inogatran, and efegatran. Ximelagatran (Exanta) is new oral agent that is showing great promise for protection against stroke in patients with atrial fibrillation while posing a low risk for bleeding.

All anti-clotting drugs carry a risk for bleeding and a slightly increased risk for hemorrhagic stroke.

Drugs for Hemorrhagic Stroke

Calcium Channel Blockers. Early administration of calcium channel blockers, such as nimodipine (Nimotop), can improve functional outcome. 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. The drugs work best if it is administered within six hours of the stroke. Calcium channel blockers are not useful for ischemic stroke, although they can be used in combinations with blood pressure lowering agents to prevent them.

Antifibrinolytic Drugs. Drugs called antifibrinolytics (e.g., tranexamic acid, epsilon amino-caproic acid or an equivalent) are used to stop bleeding. They have been investigated for years for subarachnoid hemorrhagic stroke but, at this time, they do not appear to improve outlook.

Investigative Therapies to Protect or Restore Nerve Cells after a Stroke

Nerve-Protecting Agents. More than 50 medications have been studied in clinical trials aimed at slowing down or preventing 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. Although none to date have proven to have any significant benefits, some are showing promise. They include magnesium sulfate, citicoline, ebselen, piracetam, edaravone, albumin, and erythropoietin. In a 2002 study, for example, an analysis of studies using citicoline with the first 24 hours of a stroke suggested that it increased the probability of complete recovery by about 5%. Of particular interest are animal studies suggesting that sildenafil (Viagra) may have nerve-protecting properties and help recovery from a stroke.

Investigative 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. For example, a 2002 study reported nerve regeneration in animals whose brains were treated with the agent inosine. More research is underway.