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April 1990, Vol 47, No. 4 >
Article | April 1990

The Contribution of Multicenter Trials to Stroke Prevention and Treatment

H. J. M. Barnett, MD
[+] Author Affiliations

Accepted for publication September 27, 1989.

Reprint requests to The John P. Robarts Research Institute, PO Box 5015, London, Ontario, Canada N6A 5K8 (Dr Barnett).


Arch Neurol. 1990;47(4):441-444. doi:10.1001/archneur.1990.00530040097023
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Until the second half of this decade, neurologists interested in stroke felt little need for critical studies evaluating therapeutic measures. Neither stroke prevention nor specific treatment of patients who had signs of infarction offered promise. Detailed study of individual patients was of importance mainly to assess the probable prognosis. The imaging methods of the day were inexact, uncomfortable, and not without risk. The situation has changed: there has been a dramatic decline in the occurrence of, and mortality due to, stroke; primary prevention measures collectively appear to have brought about this reduction; some effective secondary prevention measures are available now, and other new ones look promising; certain measures to reduce the brain edema associated with infarction have been found to be ineffective, if not hazardous, and we are struggling with uncertainties about the others; putative measures for brain resuscitation are undergoing animal and early clinical trials; the possibility of actively

REFERENCES

1 +
Caplan LR.  TIAs: we need to return to the question, 'what is wrong with Mr. Jones?' Neurology . 1988;;38:791-793.
2 +
Haynes RB, Mukherjee J, Sackett DL, Taylor W, Barnett HJM, Peerless SJ.  Functional status changes following medical or surgical treatment for cerebral ischemia . JAMA . 1987;;257:2043-2046.
3 +
Duke RJ, Bloch RF, Turpie AGG, Trebilcock R, Bayer N.  Intravenous heparin for the prevention of stroke progression in acute partial stable stroke: a randomized controlled trial . Ann Intern Med . 1986;;105:825-828.
4 +
Haley EC, Kassell NF, Torner JC.  Failure of heparin to prevent progression in progressing ischemic infarction . Stroke . 1988;;19:10-14.
5 +
Cerebral Embolism Study Group.  Immediate anticoagulation of embolic stroke: a randomized trial . Stroke . 1988;;14:668.
6 +
Dyken ML.  Antiplatelet aggregating agents in transient ischemic attacks and the relationship of risk factors . In: Breddin K, Loew D, Überla K, Dorndorf W, Marks R, eds. Prophylaxis of Venous, Peripheral Cardiac and Cerebral Vascular Diseases With Acetylsalicylic Acid . New York, NY: FK Schattauer Verlag; 1981;:141-148.
7 +
Canadian Cooperative Study Group.  A randomized trial of aspirin and sulfinpyrazone in threatened stroke . N Engl J Med . 1978;;299:53-59.
8 +
Bousser MG, Eschwege E, Haguenau M, et al.  'AICLA' controlled trial of aspirin and dipyridamide in the secondary prevention of antherothrombotic cerebral ischemia . Stroke . 1983;;14:5-14.
9 +
American-Canadian Cooperative Study Group.  Persantine-aspirin trial in cerebral ischemia: end-point results . Stroke . 1985;;16:406.
10 +
Gent M, Blakely JA, Hachinski V, et al.  A secondary prevention, randomized trial of suloctidil in patients with a recent history of thromboembolic stroke . Stroke . 1985;;16:416-424.
11 +
The ESPS Group.  The European Stroke Prevention Study (ESPS): principal end-points . Lancet . 1987;;2:1351-1354.
12 +
Peto R, Gray R, Collins R, et al.  Randomized trial of prophylactic daily aspirin in British male doctors . Br Med J . 1988;;296:313-316.
13 +
Gent M, Blakely JA, Easton JD, et al and the CATS Group.  The Canadian American Ticlopidine Study (CATS) in Thromboembolic Stroke . Lancet . 1989;;1:1215-1220.
14 +
Hass WK, Kamm B.  The North American Ticlopidine Aspirin Stroke Study: structure, stratification variable, and patient characteristics . In: Gordon JL, ed. Ticlopidine: Quo Vadis? Cambridge, Mass: Birkhauser Boston Inc; 1984;: 273-282.
15 +
Boysen G, Sorensen PS, Juhler M, et al.  Danish very-low-dose aspirin after carotid endarterectomy trial . Stroke . 1988;;19:1211-1215.
16 +
UK-TIA Study Group.  United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results . Br Med J . 1988;;296:316-320.
17 +
Barnett HJM.  The anticipated and the unexpected from clinical trials in stroke prevention . In: Arnold CB, ed. Transactions of the Association of Life Insurance Medical Directors of America Ninety-Seventh Annual Meeting . Tampa, Fla: Joe B Klay & Sons Inc; 1989;.
18 +
The EC/IC Bypass Study Group.  Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke: results of an international randomized trial . N Engl J Med . 1985;;313:1191-1200.
19 +
Powers WJ, Grubb RL, Raichle ME.  Clinical results of extracranial-intracranial bypass surgery in patients with hemodynamic cerebrovascular disease . J Neurosurg . 1989;;1970;61-67.
20 +
Powers WJ, Tempel LW, Grubb RL.  Influence of cerebral hemodynamics on stroke risk: one-year follow-up of 30 medically treated patients . Ann Neurol . 1985;;25:325-330.
21 +
Sundt TM.  Was the international randomized trial of extracranial-intracranial arterial bypass representative of the population at risk? N Engl J Med . 1987;;316:814-816.
22 +
Fields WS, Maslenikov V, Meyer JS, et al.  Joint study of extracranial arterial occlusion, V: progress report of prognosis following surgery or nonsurgical treatment for transient cerebral ischemic attacks and cervical carotid artery lesions . JAMA . 1970;;211:1993-2003.
23 +
Shaw DA, Venables GS, Cartilidge NEF, Bates D, Dickinson PH.  Carotid endarterectomy in patients with transient cerebral ischemia . J Neurol Sci . 1984;;64:45-53.
24 +
Kurtzke J.  Considerations in the treatment of stroke . In: Whisnant JP, Sandok BA, eds. Cerebral Vascular Diseases . New York, NY: Grune & Stratton; 1974;:190-193.
25 +
 The Extracranial-Intracranial Bypass Study: a report of the committee appointed by the American Association of Neurological Surgeons to examine the study . N Engl J Med . 1987;;316:817-820.
26 +
Meyer JS, Gilroy J, Barnhardt ME, Johnson JF.  Therapeutic thrombolysis in cerebral thromboembolism: randomized evaluation of intravenous streptokinase . In: Millikan CH, Siekert RG, Whisnant JP, eds. Cerebral Vascular Diseases: Fourth Princeton Conference . New York, NY: Grune & Stratton, 1965;:200-213.
27 +
Barnett HJM.  Delayed cerebral ischemic episodes distal to occlusion of major cerebral arteries . Neurology . 1978;;28:769-774.
28 +
Barnett HJM, Peerless SJ, Kaufmann JCE.  'Stump' of internal carotid artery: a source for further cerebral embolic ischemia . Stroke . 1978;;9:448-456.
29 +
Bogousslavsky J, Wong W, Barnett HJM.  Bilateral occlusion of the middle cerebral artery trunk . Stroke . 1986;;17:1107-1111.
30 +
Bogousslavsky J, Barnett HJM, Fox AJ, Hachinski VC.  Atherosclerotic disease of the middle cerebral artery . Stroke . 1986;;17:1112-1120.
31 +
Wade JPH, Wong W, Barnett HJM, Vandervoort P.  Bilateral occlusion of the internal carotid arteries presenting symptoms in 74 patients and a prospective study of 34 medically treated patients . Brain . 1987;;110:667-682.
32 +
Barnett HJM, Boughner DR, Taylor W, Cooper PE, Kostuk WJ, Nichol PE.  Further evidence relating mitral valve prolapse to cerebral ischemic events . N Engl J Med . 1980;;302:139-144.

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1 +
Caplan LR.  TIAs: we need to return to the question, 'what is wrong with Mr. Jones?' Neurology . 1988;;38:791-793.
2 +
Haynes RB, Mukherjee J, Sackett DL, Taylor W, Barnett HJM, Peerless SJ.  Functional status changes following medical or surgical treatment for cerebral ischemia . JAMA . 1987;;257:2043-2046.
3 +
Duke RJ, Bloch RF, Turpie AGG, Trebilcock R, Bayer N.  Intravenous heparin for the prevention of stroke progression in acute partial stable stroke: a randomized controlled trial . Ann Intern Med . 1986;;105:825-828.
4 +
Haley EC, Kassell NF, Torner JC.  Failure of heparin to prevent progression in progressing ischemic infarction . Stroke . 1988;;19:10-14.
5 +
Cerebral Embolism Study Group.  Immediate anticoagulation of embolic stroke: a randomized trial . Stroke . 1988;;14:668.
6 +
Dyken ML.  Antiplatelet aggregating agents in transient ischemic attacks and the relationship of risk factors . In: Breddin K, Loew D, Überla K, Dorndorf W, Marks R, eds. Prophylaxis of Venous, Peripheral Cardiac and Cerebral Vascular Diseases With Acetylsalicylic Acid . New York, NY: FK Schattauer Verlag; 1981;:141-148.
7 +
Canadian Cooperative Study Group.  A randomized trial of aspirin and sulfinpyrazone in threatened stroke . N Engl J Med . 1978;;299:53-59.
8 +
Bousser MG, Eschwege E, Haguenau M, et al.  'AICLA' controlled trial of aspirin and dipyridamide in the secondary prevention of antherothrombotic cerebral ischemia . Stroke . 1983;;14:5-14.
9 +
American-Canadian Cooperative Study Group.  Persantine-aspirin trial in cerebral ischemia: end-point results . Stroke . 1985;;16:406.
10 +
Gent M, Blakely JA, Hachinski V, et al.  A secondary prevention, randomized trial of suloctidil in patients with a recent history of thromboembolic stroke . Stroke . 1985;;16:416-424.
11 +
The ESPS Group.  The European Stroke Prevention Study (ESPS): principal end-points . Lancet . 1987;;2:1351-1354.
12 +
Peto R, Gray R, Collins R, et al.  Randomized trial of prophylactic daily aspirin in British male doctors . Br Med J . 1988;;296:313-316.
13 +
Gent M, Blakely JA, Easton JD, et al and the CATS Group.  The Canadian American Ticlopidine Study (CATS) in Thromboembolic Stroke . Lancet . 1989;;1:1215-1220.
14 +
Hass WK, Kamm B.  The North American Ticlopidine Aspirin Stroke Study: structure, stratification variable, and patient characteristics . In: Gordon JL, ed. Ticlopidine: Quo Vadis? Cambridge, Mass: Birkhauser Boston Inc; 1984;: 273-282.
15 +
Boysen G, Sorensen PS, Juhler M, et al.  Danish very-low-dose aspirin after carotid endarterectomy trial . Stroke . 1988;;19:1211-1215.
16 +
UK-TIA Study Group.  United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results . Br Med J . 1988;;296:316-320.
17 +
Barnett HJM.  The anticipated and the unexpected from clinical trials in stroke prevention . In: Arnold CB, ed. Transactions of the Association of Life Insurance Medical Directors of America Ninety-Seventh Annual Meeting . Tampa, Fla: Joe B Klay & Sons Inc; 1989;.
18 +
The EC/IC Bypass Study Group.  Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke: results of an international randomized trial . N Engl J Med . 1985;;313:1191-1200.
19 +
Powers WJ, Grubb RL, Raichle ME.  Clinical results of extracranial-intracranial bypass surgery in patients with hemodynamic cerebrovascular disease . J Neurosurg . 1989;;1970;61-67.
20 +
Powers WJ, Tempel LW, Grubb RL.  Influence of cerebral hemodynamics on stroke risk: one-year follow-up of 30 medically treated patients . Ann Neurol . 1985;;25:325-330.
21 +
Sundt TM.  Was the international randomized trial of extracranial-intracranial arterial bypass representative of the population at risk? N Engl J Med . 1987;;316:814-816.
22 +
Fields WS, Maslenikov V, Meyer JS, et al.  Joint study of extracranial arterial occlusion, V: progress report of prognosis following surgery or nonsurgical treatment for transient cerebral ischemic attacks and cervical carotid artery lesions . JAMA . 1970;;211:1993-2003.
23 +
Shaw DA, Venables GS, Cartilidge NEF, Bates D, Dickinson PH.  Carotid endarterectomy in patients with transient cerebral ischemia . J Neurol Sci . 1984;;64:45-53.
24 +
Kurtzke J.  Considerations in the treatment of stroke . In: Whisnant JP, Sandok BA, eds. Cerebral Vascular Diseases . New York, NY: Grune & Stratton; 1974;:190-193.
25 +
 The Extracranial-Intracranial Bypass Study: a report of the committee appointed by the American Association of Neurological Surgeons to examine the study . N Engl J Med . 1987;;316:817-820.
26 +
Meyer JS, Gilroy J, Barnhardt ME, Johnson JF.  Therapeutic thrombolysis in cerebral thromboembolism: randomized evaluation of intravenous streptokinase . In: Millikan CH, Siekert RG, Whisnant JP, eds. Cerebral Vascular Diseases: Fourth Princeton Conference . New York, NY: Grune & Stratton, 1965;:200-213.
27 +
Barnett HJM.  Delayed cerebral ischemic episodes distal to occlusion of major cerebral arteries . Neurology . 1978;;28:769-774.
28 +
Barnett HJM, Peerless SJ, Kaufmann JCE.  'Stump' of internal carotid artery: a source for further cerebral embolic ischemia . Stroke . 1978;;9:448-456.
29 +
Bogousslavsky J, Wong W, Barnett HJM.  Bilateral occlusion of the middle cerebral artery trunk . Stroke . 1986;;17:1107-1111.
30 +
Bogousslavsky J, Barnett HJM, Fox AJ, Hachinski VC.  Atherosclerotic disease of the middle cerebral artery . Stroke . 1986;;17:1112-1120.
31 +
Wade JPH, Wong W, Barnett HJM, Vandervoort P.  Bilateral occlusion of the internal carotid arteries presenting symptoms in 74 patients and a prospective study of 34 medically treated patients . Brain . 1987;;110:667-682.
32 +
Barnett HJM, Boughner DR, Taylor W, Cooper PE, Kostuk WJ, Nichol PE.  Further evidence relating mitral valve prolapse to cerebral ischemic events . N Engl J Med . 1980;;302:139-144.

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