Stroke ischemic treatment

Overview
Treatment of stroke is occasionally with thrombolysis ("clot buster"), but usually with supportive care (physiotherapy and occupational therapy) and secondary prevention with antiplatelet drugs (aspirin and often dipyridamole), blood pressure control, statins and anticoagulation (in selected patients).

Treatment of Ischemic stroke
An ischemic stroke is due to a thrombus (blood clot) occluding a cerebral artery, a patient is given antiplatelet medication (aspirin, clopidogrel, dipyridamole), or anticoagulant medication (warfarin), dependent on the cause, when this type of stroke has been found. Hemorrhagic stroke must be ruled out with medical imaging, since this therapy would be harmful to patients with that type of stroke.

Whether thrombolysis is performed or not, the following investigations are required:
 * Stroke symptoms are documented, often using scoring systems such as the National Institutes of Health Stroke Scale, the Cincinnati Stroke Scale, and the Los Angeles Prehospital Stroke Screen. The Cincinnati Stroke Scale is used by emergency medical technicians (EMTs) to determine whether a patient needs transport to a stroke center.
 * A CT scan is performed to rule out hemorrhagic stroke
 * Blood tests, such as a full blood count, coagulation studies (PT/INR and APTT), and tests of electrolytes, renal function, liver function tests and glucose levels are carried out.

Other immediate strategies to protect the brain during stroke include ensuring that blood sugar is as normal as possible (such as commencement of an insulin sliding scale in known diabetics), and that the stroke patient is receiving adequate oxygen and intravenous fluids. The patient may be positioned so that his or her head is flat on the stretcher, rather than sitting up, since studies have shown that this increases blood flow to the brain. Additional therapies for ischemic stroke include aspirin (50 to 325 mg daily), clopidogrel (75 mg daily), and combined aspirin and dipyridamole extended release (25/200 mg twice daily).

It is common for the blood pressure to be elevated immediately following a stroke. Studies indicated that while high blood pressure causes stroke, it is actually beneficial in the emergency period to allow better blood flow to the brain.

If studies show carotid stenosis, and the patient has residual function in the affected side, carotid endarterectomy (surgical removal of the stenosis) may decrease the risk of recurrence if performed rapidly after stroke.

If the stroke has been the result of cardiac arrhythmia with cardiogenic emboli, treatment of the arrhythmia and anticoagulation with warfarin or high-dose aspirin may decrease the risk of recurrence. Stroke prevention treatment for a common arrhythmia, atrial fibrillation, is determined according to the CHADS/CHADS2 system.

Anticoagulant recommendations following ischemic stroke
Currently, the European Stroke Organization recommends that anticoagulation should not be used after non-cardio-embolic ischemic stroke, except in some specific situations, such as aortic atheromas, fusiform aneurysms of the basilar artery, cervical artery dissection, or patent foramen ovale in the presence of proven deep vein thrombosis (DVT) or atrial septal aneurysm. Data suggest that oral anticoagulation after non-cardiac ischemic stroke is not superior to aspirin, but may be associated with more bleeding.

The 2007 American Heart Association (AHA) / American Stroke Association (ASA) Guidelines state the following: 1. Urgent anticoagulation with the goal of preventing early recurrent stroke, halting neurological worsening, or improving outcomes after acute ischemic stroke is not recommended for treatment of patients with acute ischemic stroke (Class III, Level of Evidence A). This recommendation may change if additional data demonstrate the usefulness of very early intravenous administration of anticoagulants for treatment of patients with infarctions secondary to large-artery thrombosis or cardioembolism. Urgent anticoagulation should not be used in lieu of intravenous thrombolysis for treatment of otherwise eligible patients (Class III, Level of Evidence A).

2. Urgent anticoagulation is not recommended for patients with moderate to severe strokes because of an increased risk of serious intracranial hemorrhagic complications (Class III, Level of Evidence A).

3. Initiation of anticoagulant therapy within 24 hours of treatment with intravenously administered rtPA is not recommended (Class III, Level of Evidence B).

Antiplatelet recommendations following ischemic stroke
Although the combination of clopidogrel and aspirin is prescribed for patients with acute coronary syndromes (ACS), this combination has not been studied in the setting of acute ischemic stroke. No data are available about the use of other combinations of antiplatelet agents in the management of acute ischemic stroke. The current American Stroke Association (ASA) / American Heart Association (AHA) recommendations are the following:


 * "The administration of clopidogrel alone or in combination with aspirin is not recommended for the treatment of acute ischemic stroke (Class III, Level of Evidence C)."

The 2008 American College of Chest Physician (ACCP) Guidelines, similar to the AHA/ASA Guidelines, state the following:


 * 4.1.3. "In most patients with a noncardioembolic stroke or transient ischemic attack, were recommend avoiding long-term use of the combination of aspirin and clopidogrel (Grade1B). In those with a recent acute myocardial infarction, other acute coronary syndrome, or a recently placed coronary stent, we recommend clopidogrel plus aspirin (75-100mg) [Grade1A]."

There is no data available regarding the safety and efficacy of dual antiplatelet therapy in addition to chronic anticoagulation for patients with non-cardio-embolic-ischemic stroke. It should be noted that more potent platelet inhibition with prasugrel was associated with a higher risk of adverse outcomes compared to clopidogrel in the Triton study among patients who had sustained a prior stroke or transient ischemic attack (TIA).

Thrombolysis
In increasing numbers of primary stroke centers, pharmacologic thrombolysis ("clot busting") with the drug tissue plasminogen activator, tPA, is used to dissolve the clot and unblock the artery. However, the use of tPA in acute stroke is controversial. On one hand, it is endorsed by the American Heart Association and the American Academy of Neurology as the recommended treatment for acute stroke within three hours of onset of symptoms as long as there are not other contraindications (such as abnormal lab values, high blood pressure, or recent surgery). This position for tPA is based upon the findings of two studies by one group of investigators which showed that tPA improves the chances for a good neurological outcome. When administered within the first three hours, 39% of all patients who were treated with tPA had a good outcome at three months, only 26% of placebo controlled patients had a good functional outcome. However, in the NINDS trial 6.4% of patients with large strokes developed substantial brain hemorrhage as a complication from being given tPA. tPA is often misconstrued as a "magic bullet" and it is important for patients to be aware that despite the study that supports its use, some of the data were flawed and the safety and efficacy of tPA is controversial. A recent study found the mortality to be higher among patients receiving tPA versus those who did not. Additionally, it is the position of the American Academy of Emergency Medicine that objective evidence regarding the efficacy, safety, and applicability of tPA for acute ischemic stroke is insufficient to warrant its classification as standard of care. Until additional evidence clarifies such controversies, physicians are advised to use their discretion when considering its use. Given the cited absence of definitive evidence, AAEM believes it is inappropriate to claim that either use or non-use of intravenous thrombolytic therapy constitutes a standard of care issue in the treatment of stroke.

Mechanical thrombectomy
Another intervention for acute ischemic stroke is removal of the offending thrombus directly. This is accomplished by inserting a catheter into the femoral artery, directing it into the cerebral circulation, and deploying a corkscrew-like device to ensnare the clot, which is then withdrawn from the body. In August 2004, based on data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Trial, the FDA cleared several of these devices, called the Merci X5 and X6 Retrievers. The newer generation Merci L5 Retriever was additionally used in the Multi MERCI trial. Both the MERCI and Multi MERCI trials required the first pass with the Merci Retriever to be initiated within 8 hours of onset of symptoms.

Embolic stroke
Anticoagulation can prevent recurrent stroke. Among patients with nonvalvular atrial fibrillation, anticoagulation can reduce stroke by 60% while antiplatelet agents can reduce stroke by 20%. . However, a recent meta-analysis suggests harm from anti-coagulation started early after an embolic stroke.