For patients who have contraindications or choose not to initiate anticoagulation, the combination of aspirin (ASA) and clopidogrel is a reasonable alternative. Timing of the initiation of oral anticoagulation should be between one and two weeks after the stroke. Patients with extensive infarction or hemorrhagic transformation should delay starting oral anticoagulation, with no exact timeline. Long-term antithrombotic therapy is contraindicated in patients with history of a symptomatic primary intracerebral hemorrhage.2 New guidelines also recommend full anticoagulation for patients with symptomatic cerebral venous sinus thrombosis.
The panel did not make any recommendations regarding statin usage. In several studies, findings showed that statins reduced infarct size and had improved outcome in all stroke types.4
Prior to the 2012 update, the last guideline for antithrombotic and thrombolytic therapy for ischemic stroke was published by the ACCP in the June 2008 issue of Chest.5 Dating back to 2001, medications included r-tPA administration within three hours of stroke symptom onset, and aspirin, clopidogrel, or a com bination of aspirin and extended-release dipyridamole for stroke prophylaxis.
The management of stroke continues to focus on early intervention and secondary prevention. Thrombolytic therapy is an effective treatment of acute ischemic stroke if given within the narrow window from onset of stroke symptoms up to 4.5 hours, with the goal of treatment within a three-hour window. Beyond this time constraint, the risk outweighs the benefit of using r-tPA except in the case of intra-arterial r-tPA administration for proximal cerebral artery occlusion.
In 2010, a meta-analysis supported this by showing that the risk of death increased significantly in patients receiving r-tPA beyond 4.5 hours. Therefore, antiplatelet therapy is the best alternative for patients ineligible for thrombolytic therapy.6 Even so, that study offered little data for patients with mechanical heart valves or intracardiac thrombi. Thus, the choice for acute anticoagulation therapy is variable and uncertain. If the hemorrhagic risk is low, anticoagulation can be considered in this subgroup, but no specific guideline endorsement was made.
In 2011, the AHA/ASA published an updated treatment guideline for patients with stroke or TIA. This was an update to 2007 guidelines that outlined the early management of ischemic stroke and affirmed the benefit of IV r-tPA at 4.5 hours for the treatment of stroke.7 Of note, IV r-tPA is only FDA-approved for treatment of acute ischemic stroke within the previously recommended three-hour period from symptom onset.
Aspirin has been found to be effective in both early treatment of acute ischemic stroke and secondary prevention. The CAST trial showed a statistically significant rate of reduction of nonfatal strokes with the use of aspirin. Other antiplatelet agents, including clopidogrel and dipyridamole, can be used. The FASTER trial compared aspirin alone versus aspirin plus clopidogrel, with no difference in outcome measures, although the MATCH trial found a larger risk of hemorrhagic and bleeding complications in the acetylsalicylic acid (ASA)-plus-clopidogrel group.6,7
In TIA or stroke patients, clopidogrel is not superior to ASA in preventing recurrent stroke. However, patients who have peripheral artery disease (PAD), previous coronary artery bypass grafting (CABG), insulin dependent diabetes mellitus (IDDM), or recurrent vascular events show a benefit of transitioning from ASA to clopidogrel for secondary long-term prevention. Clopidogrel or aspirin/extended-release dipyridamole is preferred over aspirin alone or cilostazol for long-term treatment in patients with a history of noncardioembolic ischemic stroke or TIA based on the PROFESS trial.2,7
The 2012 guidelines are a resource available to hospitalists for treating acute ischemic stroke either alone or with neurology consultation. These guidelines further define the timing of r-tPA and the use of both anticoagulation and antiplatelet therapy in the proper clinical settings.