Medical Treatment of Cerebral Infarction

Choi, Young Bin; Lee, Kwang Soo

Abstract

Anticoagulants and antiplatelet agents have been widely used and studied in both the management of acute stroke and for stroke prevention. The use of anticoagulants and antiplatelet agents in acute ischemic stroke is aimed at preventing stroke recurrence and reducing stroke progression. Studies examining unfractionated heparin following acute ischemic stroke failed to show an overall benefit. Reductions in thromboembolic events and progression of stroke were offset by an increased risk of major bleeding including intracerebral hemorrhage. Low molecular weight heparin compounds and hepanoids in acute ischemic stroke similarly have failed to prove overall benefit when bleeding complications, especially intracerebral hemorrhage, are considered along with reductions in thromboembolic complications. Ancrod, an agent capable of reducing circulating fibrinogen levels has been shown in clinical trials to improve outcome following stroke when administered within three ours of stroke onset. Antiplatelet agents have been evaluated in acute ischemic stroke. The largest studies have examined the role of aspirin therapy (IST, CAST). Studies have shown a small but statistically significant improvement in the aspirin-treated patients treated within 48 hours. Abciximab, a IIB/IIIA inhibitor, has been studied in acute ischemic stroke with an acceptable safety profile and encouraging findings of potential benefit. These studies have led to an ongoing trial of Abciximab (ReoPro) in acute ischemic stroke. Other ongoing clinical trials in acute ischemic stroke include studies of clopidogrel following TIA and unfractionated heparin in acute ischemic stroke. Antithrombotic agents are widely used for stroke prevention. Long-term oral anticoagulation has been proven of benefit in the prevention of stroke in high risk patients with atrial fibrillation. Two large clinical trials in high risk patients with atrial fibrillation have examined a direct thrombin inhibitor, Ximelagatran, compared to warfarin for stroke prevention. These studies have shown similar thromboembolic events with Ximelagatran comparable to warfarin. The risks of bleeding were reduced with Ximelagatran as compared to warfarin treatment. Ximelagatran does not require regular monitoring of coagulation or dose adjustments. There is an increased risk of liver enzyme abnormalities in some patient receiving Ximelagatran. Antiplatelet agents are the mainstay of antithrombotic therapy for secondary stroke prevention with four agents currently approved for use (aspirin, ticlopidine, clopidogrel, and extended release dipyridamole plus aspirin). A number of studies are underway examining the role of antiplatelet agents in combination or for additional indications. These studies include MATCH, CHARISMA, SPS3, ARCH, CARESS, PROFESS, and WASID.