Along with aspirin, other antiplatelet agents have been studied, most commonly dipyridamole and clopidrogel. The EARLY trial demonstrated no significant differences in the aspirin and dipyridamole groups at 90 days.3
Another large trial, which focused on clopidrogel and aspirin, looked at aspirin plus clopidrogel or aspirin alone. The FASTER trial enrolled mostly patients with mild cerebrovasular accidents (CVA) or transient ischemic attacks (TIA), and there was no difference in outcome measures between the groups.4 However, the MATCH trial found that aspirin and clopidrogel did not provide improved stroke preventions versus clopidogrel alone but had a larger risk of hemorrhagic/bleeding complications.5
Aspirin dosage is somewhat controversial. Fewer side effects occur with lower doses. Combining the trials, consensus treatment includes early aspirin dosing (325 mg initially, then 150 mg-325 mg daily) given to patients with ischemic stroke. Early aspirin should be avoided in those patients who qualify for and are receiving alteplase, heparin, or oral warfarin therapy.
There are other antiplatelet agents for long-term management of ischemic stroke. Whereas aspirin alone is used in the early management of acute ischemic stroke in those ineligible for thrombolytic therapy, many patients are transitioned to other antiplatelet strategies for secondary prevention long-term. The number needed to treat for aspirin to reduce one future stroke, myocardial infarction (MI), or vascular death when compared to placebo is quite high at 33. However, the combination of aspirin and dipyradimole does not prevent MI, vascular death, or the combined endpoint of either stroke or death.
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Table 1. Summary of major trials
Clopidogrel is more effective than aspirin in preventing a combined endpoint of ischemic stroke, MI, or vascular death, but it is not superior to aspirin in preventing recurrent stroke in TIA or stroke patients. The effects of clopidrogel are greater in patients with peripheral arterial disease, previous coronary artery bypass grafting, insulin-dependent diabetes, or recurrent vascular events.
There is a substantially high cost of treatment and long-term disability associated with stroke. Costs can vary from 3% to 5% of the annual healthcare budget. The newer antiplatelet agents are more expensive than aspirin, and overall cost-effectiveness is difficult to estimate. Yet, from an economic standpoint, the combination of aspirin and dipyradimole can be recommended as an alternative for secondary stroke prevention in patients without major comorbidities. In those patients with higher risk factors and/or comorbidities, clopidogrel might be more cost-effective than aspirin alone. Furthermore, in patients with aspirin intolerance, clopidogrel is a useful, but expensive, alternative.
Thrombolytic therapy. Restora-tion of blood flow with thrombolytic therapy is the most effective way of salvaging ischemic brain tissue that has not already infarcted. The window for use of the thrombolytic alteplase is narrow; studies suggest that its benefit diminishes with increasing time to treatment. Indeed, after 4.5 hours from the onset of symptoms, evidence suggests that the harm might outweigh the benefit, so the determination of who is eligible for its use has to be made quickly.
Guidelines published by the American Heart Association/American Stoke Association stroke council outline strict inclusion and exclusion criteria for the use of alteplase in the management of acute ischemic stroke.6 Obtaining informed consent and emergent neuroimaging are vital in preventing delays in alteplase administration.
Two major trials that illustrate the benefit of alteplase in the treatment of acute ischemic stroke are the NINDS trial and the ECASS 3 trial. NINDS showed that when intravenous alteplase was used within three hours of symptom onset, patients had improved functional outcome at three months.7 The ECASS 3 trial showed that intravenous alteplase has benefit when given up to 4.5 hours after symptom onset.8 Treatment with intravenous alteplase from three-4.5 hours in the ECASS 3 trial showed a modest improvement in patient outcomes at three months, with a number needed to treat of 14 for a favorable outcome.