Antithrombotic and Neuroprotective Therapy in Acute Ischemic Stroke

Sung Hyuk Heo; Dae-Il Chang

doi:10.5124/jkma.2009.52.4.356

J Korean Med Assoc > Volume 52(4); 2009 > Article

Heo and Chang: Antithrombotic and Neuroprotective Therapy in Acute Ischemic Stroke

Focused Issue of This Month

Acute Management of Stroke

Journal of the Korean Medical Association

Journal of the Korean Medical Association 2009; 52(4): 356-364.

Published online: April 30, 2009

DOI: http://dx.doi.org/10.5124/jkma.2009.52.4.356

Antithrombotic and Neuroprotective Therapy in Acute Ischemic Stroke

Sung Hyuk Heo, MD, Dae-Il Chang, MD

Department of Neurology, Kyung Hee University College of Medicine, Korea. dichang@khmc.or.kr

Abstract

As, until now, many studies have failed to establish the clinical effect of numerous neuroprotectives, antithrombotic therapy must be emphasized as one of critical options among limited treatment strategies in acute ischemic stroke. Based on the accumulating evidences that platelets and coagulating proteins play an important role in the thrombus formation, antiplatelets and anticoagulants are served as antithrombotics. Recently, major advances have been made in understanding the effects of antiplatelets and anticoagulants. Large randomized clinical trials have highlighted the effectiveness and safety of early and continuous antiplatelet therapy in reducing atherothrombotic stroke recurrence. Urgent anticoagulation has been used often to prevent early recurrent stroke and to improve neurological outcomes, however, its formal use in acute stroke has been the subject of debate even in cardioembolic stroke. That's because anticoagulants also increase the risk of fatal or disabling intracranial hemorrhage and it is difficult to monitor proper anticoagulation. Although early administration of anticoagulants should be considered to prevent the secondary injury and the propagation of thrombosis in patients with atherothrombotic stroke, more evidences are needed especially in patients with infractions secondary to large artery thrombosis or cardioembolism. This review discusses recent advances related to antithrombotic strategies and putative neuroprotectives.

Acute stroke; Antithrombotic therapy; Antiplatelet; Anticoagulant; Neuroprotective

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Figure 1

Absolute effects in CAST and IST of early use of aspirin in 40,000 randomized patients with suspected acute ischemic stroke. Numbers and percentages of patients with various outcomes during the scheduled treatment period, by allocated treatment: A indicates aspirin; C, control. The percentages are plotted as bars (with the SD of each bar plotted at the top). The difference between aspirin and control is given as the benefit per 1,000, along with its SD and statistical significance (2P). A negative benefit indicates an apparent hazard. *Number of patients who experienced the relevant event and survived (Stroke 2000; 31: 1240-1249).

Table 1

Characteristics of the two large trials of the early use of aspirin in acute ischemic stroke: CAST and IST (Stroke 2000; 31: 1240-1249)

IST was as 2X2 'factorial' trial of aspirin, heparin, neither, or both: of those allocated to receive heparin in IST, half were to receive 5,000U BID and half were to receive 12,500U unfractionated heparin SC BID.

Table 2

Recent trials of emergent lower-molecular-weight heparin and danaparoid for acute ischemic stroke

FISS: the Fraxiparine in Ischemic Stroke, Study, TOAST: the Trials of ORG 10172 in Acute Stroke Treatment, TAIST: Tinzaparin in Acute Ischemic Stroke Trial, TOPAS: Therapy Of Patients with Acute Stroke, HAEST: Heparin in Acute Embolic Stroke Trial, GOS: Glasgow Outcome Scale, MBI: Modified Barthel Index, AIS: acute ischemic stroke, LAD: large artery atherosclerotic disease.