SEMINARS I N NEUKOLO(;Y-VOLUME
11,
NO. 4 Dt.;Cb;:'MBEK
1991
ANTITHROMBOTIC THERAPY FOR ISCHEMIC CEREBROVASCULAR DISEASE
Cerebrovascular disease ranks third as a cause of death and is a leading cause of' long-term disability in much of the industrialized world. Kecognition of these facts has stimulated considerable interest in new approaches to its prevention and treatment. Antithrombotic agents are widely used for the treatment of ischemic cerebrovascular disease. 'These drugs are prescribed to prevent recurrent embolization o r thrombus propagation, maintain collateral circulation to the ischemic area, and tlecrease the risk of' major complications of' ischemic stroke such as systemic venous thromboernbolisrri. 'l'he purpose of'this review is to present a perspective, based on clinical trial results, on the use of selective antithrombotic agents (aspirin, ticlopidine, heparin, low molecular weight heparinoids) and the defibrinating agent ancrod.
ANTIPLATELET AGENTS ASPIRIN
Aspirin is thc standard medical therapy used filr prevention in patients threatened with stroke. I t irreversibly inhibits platelet function by inactivating cyclooxygenase. Both primary and secondary prevention studies have evaluated its efficacy in cerebrovascular disease.
Primary Prevention Tivo primary prevention studies have assessed the role of' aspirin in preventing vascular events in asymptomatic individuals. In the United Kingdom study, 5 139 male physicians received either aspirin
500 mglday o r no treatment.' There was no significant difference in vascular mortality between the two groups. Another trial, the American Physicians' Health Study, enrolled 22,071 physicians and compared aspirin 325 mg every other day to placebo in the prevention of cardiovascular rnortality and stroke.%yocardial infjrction (MI) was reduced by 445% in the aspirin-treated group. There was inconclusive evidence regarding the effect of' aspirin in reducing stroke because of the small number of stroke endpoints. When the endpoints of nonf'atal M I , nonfatal stroke, and cardiovascular death were combined, there was an 18% risk reduction with aspirin when compared with placebo.
Secondary Prevention There have been many studies evaluating the use of various antiplatelet agents for the secondary prevention of' cerebral infarction after cerebral ischemic events. These studies are sumnlarized in 'lable 1. T h e first double-blind, placebo-controlled trial of aspirin for stroke prevention in the United States was perfhrmed in 1977." T h e study enrolled 178 patients (66%' men, 34% women) with carotid distribution transient ischemic attacks (TIAs). Considering the absolute endpoints of mortality, cerebral and retinal infarction, there was no statistically signif'icant difference between the aspirin and placebo groups. In the aspirin-treated group, 1 1 of 88 patients (13%) had a stroke compared to 14 o f 9 0 in the placebo (16%) group. However, aspirin was superior to placebo in preventing the combined endpoints of mortality, cerebral infarction, and retinal infarction in patients with fre-
Division of Ckreb~-ov;~scular I)ise;rscs, Department of' Neurology, U ~ ~ i v e r s iof t y Iowa (:ollcge of'hletlici~le,Iowa City, Iowa Kcpril~tI-equests: Dr. Killer, Stroke Program, Department of Ncul-ology, Ko~-th\veste~-n li~~iversity hlcclical School, 233 East Eric, Suite 500, Chicago, Illinois 6061 I Copyright 0 1991 by l'hieme Medical Publishers, Inc., 381 Park Avenue S o ~ ~ t New h , York, NY 100ICi. All rights reserved.
Downloaded by: Universite Laval. Copyrighted material.
josd Biller, M.D. F.A.C. P., Betsy B. Love, M.D., and David Lee (hrdor~,M.D.
Table 1. Studies of Aspirin in Secondary Prevention of Cerebral Ischemia* No. Patients
Diagnosis
Timing of Entry
FoIIow-UP
Groups
Results
Carotid TIA
11,
NO. 4 Dt.;Cb;:'MBEK
1991
ANTITHROMBOTIC THERAPY FOR ISCHEMIC CEREBROVASCULAR DISEASE
Cerebrovascular disease ranks third as a cause of death and is a leading cause of' long-term disability in much of the industrialized world. Kecognition of these facts has stimulated considerable interest in new approaches to its prevention and treatment. Antithrombotic agents are widely used for the treatment of ischemic cerebrovascular disease. 'These drugs are prescribed to prevent recurrent embolization o r thrombus propagation, maintain collateral circulation to the ischemic area, and tlecrease the risk of' major complications of' ischemic stroke such as systemic venous thromboernbolisrri. 'l'he purpose of'this review is to present a perspective, based on clinical trial results, on the use of selective antithrombotic agents (aspirin, ticlopidine, heparin, low molecular weight heparinoids) and the defibrinating agent ancrod.
ANTIPLATELET AGENTS ASPIRIN
Aspirin is thc standard medical therapy used filr prevention in patients threatened with stroke. I t irreversibly inhibits platelet function by inactivating cyclooxygenase. Both primary and secondary prevention studies have evaluated its efficacy in cerebrovascular disease.
Primary Prevention Tivo primary prevention studies have assessed the role of' aspirin in preventing vascular events in asymptomatic individuals. In the United Kingdom study, 5 139 male physicians received either aspirin
500 mglday o r no treatment.' There was no significant difference in vascular mortality between the two groups. Another trial, the American Physicians' Health Study, enrolled 22,071 physicians and compared aspirin 325 mg every other day to placebo in the prevention of cardiovascular rnortality and stroke.%yocardial infjrction (MI) was reduced by 445% in the aspirin-treated group. There was inconclusive evidence regarding the effect of' aspirin in reducing stroke because of the small number of stroke endpoints. When the endpoints of nonf'atal M I , nonfatal stroke, and cardiovascular death were combined, there was an 18% risk reduction with aspirin when compared with placebo.
Secondary Prevention There have been many studies evaluating the use of various antiplatelet agents for the secondary prevention of' cerebral infarction after cerebral ischemic events. These studies are sumnlarized in 'lable 1. T h e first double-blind, placebo-controlled trial of aspirin for stroke prevention in the United States was perfhrmed in 1977." T h e study enrolled 178 patients (66%' men, 34% women) with carotid distribution transient ischemic attacks (TIAs). Considering the absolute endpoints of mortality, cerebral and retinal infarction, there was no statistically signif'icant difference between the aspirin and placebo groups. In the aspirin-treated group, 1 1 of 88 patients (13%) had a stroke compared to 14 o f 9 0 in the placebo (16%) group. However, aspirin was superior to placebo in preventing the combined endpoints of mortality, cerebral infarction, and retinal infarction in patients with fre-
Division of Ckreb~-ov;~scular I)ise;rscs, Department of' Neurology, U ~ ~ i v e r s iof t y Iowa (:ollcge of'hletlici~le,Iowa City, Iowa Kcpril~tI-equests: Dr. Killer, Stroke Program, Department of Ncul-ology, Ko~-th\veste~-n li~~iversity hlcclical School, 233 East Eric, Suite 500, Chicago, Illinois 6061 I Copyright 0 1991 by l'hieme Medical Publishers, Inc., 381 Park Avenue S o ~ ~ t New h , York, NY 100ICi. All rights reserved.
Downloaded by: Universite Laval. Copyrighted material.
josd Biller, M.D. F.A.C. P., Betsy B. Love, M.D., and David Lee (hrdor~,M.D.
Table 1. Studies of Aspirin in Secondary Prevention of Cerebral Ischemia* No. Patients
Diagnosis
Timing of Entry
FoIIow-UP
Groups
Results
Carotid TIA
