- Email: [email protected]
7. Clinical trials (medical)
SECOND WORLD CONGRESS OF STROKE, 1992
S13
SY19
SY18 Angiogenic Events in Neural Transplantation Jeffrey M. Rosenstein and Janette M. Krum, The George Washington University Medical Center, Washington, D.C., U.S.A.
Rapid vascular integration between transplanted neural tissues and host brain is essential to prevent ischemic damage and ensure long-term survival. This presentation wiII examine the mechanism of angiogenesis in both autonomic and fetal CNS transplants. In autonomic grafts such as ganglia or adrenal meduIla, the intrinsic vessels retain both morphological and physiological properties which usually leads to deficit in the blood-brain barrier (BBB). These transplants stimulate the growth of host vessels to a greater degree than injury alone but few of the neovessels enter the tissue and vascularization takes place at the interface. The vasculature in a CNS transplant, however, is a combination of the actively growing fetal vessels and the regenerating vascular sprouts that invade from the host. The new angio-architecture within transplants wiII be discussed with regard to BBB properties, astroglial relations, extraceIlular matrix components and endothelial ceIl proteins.
Fibrinolysis in acute stroke: progress report Werner Hacke, Heidelberg, Germany The rationale for the use of thrombolytic substances in acute cerebral ischemia, and the results of recent studies in acute stroke patients will be reviewed. The results of open efficacy and safety studies in acute hemispheric and brain stem stroke will be reported. Special emphasis will be put upon the correlation between recanalization and clinic outcome. Data from the Heidelberg MCA-rtPA study (von KUDmer and Hacke, Stroke 1992, in press), which included 32 patients with hemispheric stroke caused by angiographic proven middle cerebral artery occlusion will be presented. Complete or partial reperfusion was observed in 17 patients within 12-24h after stroke onset. Recanalisation was significantly associated with favourable outcome. Additionally, the presence of good meningeal collaterals was assossiated with good outcome. Finally, the design of an ongoing placebo controlled. European rtPA acute stroke trial (ECASS) will be presented.
SY20
SY21
European Stroke Prevention Study, Part I
EUROPEAN STROKE PREVENTION STUDY 2
Juhani Sivenius, Finland
ESPS 2 Group, Coordination in Belgium. 106, Jan Van Rijswijcklaan, 2018 Antwerpen
The European Stroke Prevention Study (ESPS) was a multicenter trial comparing the effect of a combination of 75 mg dipyridamole and 330 mg acetylsalicylic acid tid with placebo in the prevention of stroke or death after one or more attacks of recent «3 months) transient ischemic attack or stroke of atherothrombotic origin. In the 2.500 patients in the intention-to-treat analysis, treatment was associated with a 33.5% reduction (p
European stroke prevention study (ESPS) has shown, using the association of 75 mg dipyridamole (OP) and 330 mg aspirin (ASA) three times a day, a reduction of the end-points (stroke or death) of more than 33 % (p
SECOND WORLD CONGRESS OF STROKE, 1992
S14
SY23
SY22 Update In Stroke Prevention with Atrial Fibrillation David G. Sherman, M.D. United States
European Carotid Surgery Trial (ECST) ECST Collaborators (Europe)' presented by Professor Charles Warlow on their behalf
More than 3,600 patients with nonvalvular atrial fibrillation (NYAF) have now been studied in five randomized clinical trials examining the "efficacy and safety of warfarin or aspirin. These studies have shown that untreated disabling stroke occurs in 2.5%/yr, ischemic stroke in 5%/yr, stroke and TIA in 7%/yr and stroke, TIA and silent stroke in > 7 %/yr. Warfarin (INR 1.5-3.5) reduces ischemic brain events by about 2/3rds. There is a 1% increased risk for major bleeding with warfarin. One study showed a significant reduction in stroke with aspirin. Potential predictors of increased risk for stroke include age, hypertension, recent congestive heart failure, prior TIA or stroke, echocardiographic evidence of left ventricular dysfunction, mitral annular calcification or left atrial enlargement. Patients without these additional risk factors have a reduced risk for stroke. All patients with NVAF should receive some form of antithrombotic therapy, warfarin or aspirin. Additional studies are underway comparing therapies in these patients.
The European Carotid Surgery Trial has demonstrated in patients with a recent TIA or oild ischaemic stroke and who have mor e than 70% stenosis of the symptomatic internal carotid artery origin that a) surgery carries a serious risk b) if the patient survives surgery without stroke then the risk of ipsilateral ischaemic stroke is almost completely abolished and c) severe internal carotid artery origin atherothrombosis is the cause of most ipsilateral ischaemic strokes. The challenges now are to make surgery safer, to select patients at particularly high risk if they don't have surgery, and to devise other - a nd perhaps safer - ways of removing the lesion a t th e origin of the internal carotid artery.
SY24
SY25 Severe carotid Stenosis - Surgical Benefit and Subgroup observations
H.J.M. Barnett, M.D.
Results of a Doppler/Angiogram Validation Study Applied to Eligibility Criteria in the Asymptomatic Carotid Atherosclerosis Study (ACAS) Toole JF, Howard VJ, Chambless LE, Nelson JJ, Baker WH for the ACAS Study Group, USA
The North American Symptomatic Carotid Endarterectomy Trial determined on the basis of 331 patients with very severe stenosis given best medical care and 328 patients submitted to carotid endarterectomy that the surgical group fared significantly better at 2 years. The absolute difference between the two treatment groups for survival free of ipsilateral stroke was 17% favoring surgery. Data generated in the trial allow us to conclude that the presence of ulceration, the presentation with hemisphere (as opposed to retinal) ischemia, the age of the patient (over, rather than under 65), the presence of contralateral severe disease particularly occlusion, the existence of asymptomatic CT ischemic lesions in the TIA group, the presence of thrombus visible in the artery beyond the stenosis all contributed to a worse outlook for the medical group. Surgery was significantly beneficial for all of these high risk groups with the exception of those with thrombi beyond the stenosis visualized in the arteriogram.
ACAS is a prospective, multicenter, randomized clinical trial designed to determine whether the addition of carotid endarterectomy to aspir in plus risk factor modifications reduces the incidence of ipsilateral trans ient ischemic attacks and retinal and cerebral infarction in patients with asymptomatic carotid stenosis. The major criterion for inclusion is a hemodynamically significant stenosis (HSS) of the internal or common carotid artery based on validated test results from Doppler ultrasound, arteriography, or Doppler plus OPG-Gee. All patients in the surgery group must have arteriography before endarterectomy. ACAS developed study-wide standards for determining HSS which were consistent and designed to provide a 90-95% positive predictive value. To date, of the 467 pat ients who have thus far received the study endarterectomy, 247 had a postrandomization angiogram (the other 220 had their angiogram prerandomization). Eight percent were false positive for HSS. A small number 3/247 (1.2%) were excluded from surgery bec ause of intracranial arterial pathology found on postrandomization ang iogram.
S13
SY19
SY18 Angiogenic Events in Neural Transplantation Jeffrey M. Rosenstein and Janette M. Krum, The George Washington University Medical Center, Washington, D.C., U.S.A.
Rapid vascular integration between transplanted neural tissues and host brain is essential to prevent ischemic damage and ensure long-term survival. This presentation wiII examine the mechanism of angiogenesis in both autonomic and fetal CNS transplants. In autonomic grafts such as ganglia or adrenal meduIla, the intrinsic vessels retain both morphological and physiological properties which usually leads to deficit in the blood-brain barrier (BBB). These transplants stimulate the growth of host vessels to a greater degree than injury alone but few of the neovessels enter the tissue and vascularization takes place at the interface. The vasculature in a CNS transplant, however, is a combination of the actively growing fetal vessels and the regenerating vascular sprouts that invade from the host. The new angio-architecture within transplants wiII be discussed with regard to BBB properties, astroglial relations, extraceIlular matrix components and endothelial ceIl proteins.
Fibrinolysis in acute stroke: progress report Werner Hacke, Heidelberg, Germany The rationale for the use of thrombolytic substances in acute cerebral ischemia, and the results of recent studies in acute stroke patients will be reviewed. The results of open efficacy and safety studies in acute hemispheric and brain stem stroke will be reported. Special emphasis will be put upon the correlation between recanalization and clinic outcome. Data from the Heidelberg MCA-rtPA study (von KUDmer and Hacke, Stroke 1992, in press), which included 32 patients with hemispheric stroke caused by angiographic proven middle cerebral artery occlusion will be presented. Complete or partial reperfusion was observed in 17 patients within 12-24h after stroke onset. Recanalisation was significantly associated with favourable outcome. Additionally, the presence of good meningeal collaterals was assossiated with good outcome. Finally, the design of an ongoing placebo controlled. European rtPA acute stroke trial (ECASS) will be presented.
SY20
SY21
European Stroke Prevention Study, Part I
EUROPEAN STROKE PREVENTION STUDY 2
Juhani Sivenius, Finland
ESPS 2 Group, Coordination in Belgium. 106, Jan Van Rijswijcklaan, 2018 Antwerpen
The European Stroke Prevention Study (ESPS) was a multicenter trial comparing the effect of a combination of 75 mg dipyridamole and 330 mg acetylsalicylic acid tid with placebo in the prevention of stroke or death after one or more attacks of recent «3 months) transient ischemic attack or stroke of atherothrombotic origin. In the 2.500 patients in the intention-to-treat analysis, treatment was associated with a 33.5% reduction (p
European stroke prevention study (ESPS) has shown, using the association of 75 mg dipyridamole (OP) and 330 mg aspirin (ASA) three times a day, a reduction of the end-points (stroke or death) of more than 33 % (p
SECOND WORLD CONGRESS OF STROKE, 1992
S14
SY23
SY22 Update In Stroke Prevention with Atrial Fibrillation David G. Sherman, M.D. United States
European Carotid Surgery Trial (ECST) ECST Collaborators (Europe)' presented by Professor Charles Warlow on their behalf
More than 3,600 patients with nonvalvular atrial fibrillation (NYAF) have now been studied in five randomized clinical trials examining the "efficacy and safety of warfarin or aspirin. These studies have shown that untreated disabling stroke occurs in 2.5%/yr, ischemic stroke in 5%/yr, stroke and TIA in 7%/yr and stroke, TIA and silent stroke in > 7 %/yr. Warfarin (INR 1.5-3.5) reduces ischemic brain events by about 2/3rds. There is a 1% increased risk for major bleeding with warfarin. One study showed a significant reduction in stroke with aspirin. Potential predictors of increased risk for stroke include age, hypertension, recent congestive heart failure, prior TIA or stroke, echocardiographic evidence of left ventricular dysfunction, mitral annular calcification or left atrial enlargement. Patients without these additional risk factors have a reduced risk for stroke. All patients with NVAF should receive some form of antithrombotic therapy, warfarin or aspirin. Additional studies are underway comparing therapies in these patients.
The European Carotid Surgery Trial has demonstrated in patients with a recent TIA or oild ischaemic stroke and who have mor e than 70% stenosis of the symptomatic internal carotid artery origin that a) surgery carries a serious risk b) if the patient survives surgery without stroke then the risk of ipsilateral ischaemic stroke is almost completely abolished and c) severe internal carotid artery origin atherothrombosis is the cause of most ipsilateral ischaemic strokes. The challenges now are to make surgery safer, to select patients at particularly high risk if they don't have surgery, and to devise other - a nd perhaps safer - ways of removing the lesion a t th e origin of the internal carotid artery.
SY24
SY25 Severe carotid Stenosis - Surgical Benefit and Subgroup observations
H.J.M. Barnett, M.D.
Results of a Doppler/Angiogram Validation Study Applied to Eligibility Criteria in the Asymptomatic Carotid Atherosclerosis Study (ACAS) Toole JF, Howard VJ, Chambless LE, Nelson JJ, Baker WH for the ACAS Study Group, USA
The North American Symptomatic Carotid Endarterectomy Trial determined on the basis of 331 patients with very severe stenosis given best medical care and 328 patients submitted to carotid endarterectomy that the surgical group fared significantly better at 2 years. The absolute difference between the two treatment groups for survival free of ipsilateral stroke was 17% favoring surgery. Data generated in the trial allow us to conclude that the presence of ulceration, the presentation with hemisphere (as opposed to retinal) ischemia, the age of the patient (over, rather than under 65), the presence of contralateral severe disease particularly occlusion, the existence of asymptomatic CT ischemic lesions in the TIA group, the presence of thrombus visible in the artery beyond the stenosis all contributed to a worse outlook for the medical group. Surgery was significantly beneficial for all of these high risk groups with the exception of those with thrombi beyond the stenosis visualized in the arteriogram.
ACAS is a prospective, multicenter, randomized clinical trial designed to determine whether the addition of carotid endarterectomy to aspir in plus risk factor modifications reduces the incidence of ipsilateral trans ient ischemic attacks and retinal and cerebral infarction in patients with asymptomatic carotid stenosis. The major criterion for inclusion is a hemodynamically significant stenosis (HSS) of the internal or common carotid artery based on validated test results from Doppler ultrasound, arteriography, or Doppler plus OPG-Gee. All patients in the surgery group must have arteriography before endarterectomy. ACAS developed study-wide standards for determining HSS which were consistent and designed to provide a 90-95% positive predictive value. To date, of the 467 pat ients who have thus far received the study endarterectomy, 247 had a postrandomization angiogram (the other 220 had their angiogram prerandomization). Eight percent were false positive for HSS. A small number 3/247 (1.2%) were excluded from surgery bec ause of intracranial arterial pathology found on postrandomization ang iogram.