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Show NEURO- OPHTHALMOLOGY AT LARGE 29th International Stroke Conference, San Diego, California, February 5- 7, 2004 The 29th International Stroke Conference was held on February 5- 7, 2004, in San Diego, California. There were more than 500 abstracts presented as posters or platform presentations. Abstracts are published in Stroke 2004; 35: 235- 340. STROKE PREVENTION Patients with significant symptomatic intracranial large artery stenosis are often treated with anticoagulation, based on the results of the retrospective Warfarin Aspirin Symptomatic Intracranial Disease ( WASID) study reported in 1995 ( 1). The avidly anticipated results of the recently completed prospective WASID study were reported at the 29th International Stroke Conference. This prospective randomized multicenter study compared the effects of warfarin ( with a goal international normalized ratio [ INR] of 2- 3) versus aspirin ( 1300 mg/ d) on stroke prophylaxis inpatients with a previous transient ischemic attack or stroke referable to a major intracranial vessel with 50% to 99% stenosis. The trial was stopped early by the data safety monitoring board after enrollment of 569 patients, because of concerns related to the elevated risk of major hemorrhage in the warfarin arm. The results demonstrated that warfarin was not superior to aspirin in any of the primary or secondary outcomes, yet the rates of major hemorrhage were increased ( 8% in the warfarin arm, 3% in the aspirin arm). Intracerebral hemorrhage rates were not significantly different. Based on the results of this study, patients with symptomatic intracranial disease should be treated with antiplatelet agents rather than anticoagulation. The recently reported Warfarin Aspirin Recurrent Stroke Study ( WARSS) ( 2) failed to show the superiority of warfarin in general stroke prophylaxis. WARSS included patients with ischemic stroke from any cause except an inferred cardioem-bolic source, severe carotid artery disease in the neck for which surgery was planned, or procedure- related stroke. Taken together, the results of WASID and WARSS suggest that warfarin should be used for stroke prophylaxis only when there is a cardioembolic source. Given these data, intracranial vascular imaging may not be required to decide on an appropriate stroke prophylactic agent. However, many experts suggest that blood pressure and fluid management are best guided by this type of imaging. Currently, warfarin is typically considered the most effective treatment for prevention of emboli from atrial fibrillation, yet its use is problematic because of drug interactions and anticoagulation monitoring. The results of a study testing an alternative agent were reported at the meeting. The Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation V study ( called the SPORTIF V trial), with recruitment ending in 2001, was a double- blind, multicenter ( 409 centers in the United States and Canada) trial comparing warfarin ( with a goal INR of 2- 3) to a new agent called ximelagatran, a direct thrombin inhibitor, in stroke prophylaxis among patients with atrial fibrillation. The results showed no statistically significant difference between the two agents in prevention of stroke or systemic embolization. Intracerebral hemorrhage rates were similar. Currently, the U. S. Food and Drug Administration ( FDA) is reviewing this agent, which could provide an alternative method of anticoagulation using an agent without known drug or food interaction, and which does not require coagulation laboratory monitoring. The drug has been associated with a threefold elevation in alanine aminotransferase in 6% of patients; this side effect seems to disappear despite continuation of the medication. The significance of this enzyme elevation remains unknown. Nonetheless, ximelagatran may represent a convenient alterative to warfarin in anticoagulation for atrial fibrillation. Amlodipine and lisinopril were compared with chlorthalidone in the Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT) in 33,357 patients aged 55 years or older with hypertension and one other cardiovascular risk factor ( 3). Previously, reports had demonstrated no difference in primary cardiovascular end points among the three treatments. Secondary end points such as heart failure were lower in the thiazide group. Stroke- related outcomes were analyzed separately and reported at the meeting. Stroke occurrence, a previously specified secondary outcome, was similar in the amlodipine and chlorthalidone arms but was lower in the chlorthalidone arm than in the lisinopril arm, attributable to a difference in subgroup analysis found only in African American/ Afro- Caribbean patients. Although in this subgroup the thiazide was more effective in lowering blood pressure than was the angiotensin- converting enzyme ( ACE) inhibitor, the effect J Neuro- Ophthalmol, Vol. 24, No. 2, 2004 175 JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 Brown and Mecozzi on stroke prophylaxis was not solely due to superior blood pressure control, suggesting that in these racial groups, thiazide diuretics should be considered first- line antihypertensives. The ALLHAT results differed from results of previous studies, which had shown superiority of ACE inhibitors in stroke prophylaxis, perhaps because of the difference in racial composition of the study population. ALLHAT heightens awareness that there may be significant racial differences in treatment effects of antihypertensive agents. ACUTE ISCHEMIC STROKE Intravenous recombinant tissue- type plasminogen activator ( rt- PA) is the only FDA- approved therapy for acute stroke. Although there is a 30% improvement in excellent three- month outcome with its use, ways to improve arterial recanalization and resulting neurologic improvement are being pursued. Transcranial Doppler ( TCD) is sometimes used to monitor recanalization in patients receiving thrombolysis for large artery thrombosis. This diagnostic test may actually promote clot lysis initiated by systemically administered rt- PA, a hypothesis generated by the observation that patients being monitored with TCD seemed to have better outcomes than those not monitored. The use of ultrasound- aided thrombolysis was tested in the Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic TPA trial ( called CLOTBUST), a multicenter Phase II study randomly assigning patients to receive standard rt- PA treatment with infrequent TCD monitoring or to receive rt- PA with two hours of continuous TCD using a 2- MHz probe targeting the area of residual flow. The initial results of this study were reported. Symptomatic intracerebral hemorrhage risk was similar in both groups, suggesting that the addition of continuous TCD is safe. The primary outcome measure ( significant early clinical improvement or complete recanalization) was achieved in 30% of the group receiving rt- PA alone and in 49% of the group receiving rt- PA plus TCD. Three- month outcomes were not significantly different between the two groups. The results of this study suggest that further clinical trials of ultrasound- assisted thrombolysis are warranted in a larger group of patients with acute stroke. If future results show efficacy, ultrasound-assisted thrombolysis may become a treatment option for middle cerebral artery thromboses. There are no good data supporting the use of mechanical devices during endovascular treatment of acute stroke. The Mechanical Embolus Removal in Cerebral Ischemia ( MERCI) trial tested a thrombus retrieval device in cerebral revascularization. The initial results were reported. In this trial, a balloon- guided catheter was placed proximal to the clot, blocking forward flow. The intravascular thrombus was retrieved with a corkscrew- like device. In all, 141 patients were treated. The results of the first 114 patients were reported. Revascularization was achieved in 54%. Serious device- related complications occurred in 3.5%, including vessel perforation or dissection. Device fracture was also a problem in almost 3%. Although much more information is needed regarding the safety and efficacy of this particular device, mechanical endovascular techniques hold promise in acute stroke therapy for large vessel occlusions. Concerns continue to exist regarding the use of thrombolytics for mild stroke. An analysis using the National Institute of Neurological Disorders and Stroke ( NINDS) rt- PA Stroke Study database was undertaken to assess the benefits of rt- PA administered within 3 hours of a minor stroke. Five different definitions of minor stroke were given to capture patients with a low National Institutes of Health Stroke Scale ( NIHSS) score and those who were likely to have had a lacunar infarction. Three- month outcomes suggested benefit in the use of rt- PA in this post hoc analysis, supporting the use of intravenous thrombolytics for patients with minor stroke. Patients with stroke causing functional disability should not be excluded from treatment with intravenous rt- PA because of a low NIHSS score. INTRACEREBRAL HEMORRHAGE The role of surgery in treatment of intracerebral hemorrhage has been a controversial topic. The International Surgical Treatment of Intracerebral Hemorrhage ( ISTICH) trial compared the use of " early" surgery for intracerebral hemorrhage with initial conservative management. Patients who were thought likely to benefit from surgery were not enrolled. Patients were randomly assigned within 72 hours of the hemorrhage to receive either clot evacuation within 24 hours of randomization (" early surgery") or initial conservative care. Patients in the latter group became eligible for surgery at the discretion of their treating neurosurgeon if their condition deteriorated. Greater than 25% of the group randomly assigned to receive initial conservative management ended up having surgery. There were no significant differences between the two groups in favorable neurologic outcome or mortality. The delay in surgical treatment in the " early" surgery group because of the wide enrollment and treatment windows, as well as exclusion of those thought likely to benefit from early surgery, may help account for the lack of benefit shown from early surgical intervention. Surgical intervention for spontaneous intracerebral hemorrhage is likely to remain controversial, despite the results of this study. SUBARACHNOID HEMORRHAGE Because cooling is known to be neuroprotective, its ability to reduce ischemic injury complicating surgical clipping of aneurysms was tested. The results of the Intraoperative Hypothermia for Intracranial Aneurysm Surgery study 176 © 2004 Lippincott Williams & Wilkins 29th International Stroke Conference JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 were reported. This study was a prospective, randomized multicenter trial assessing the effect of intraoperative cooling on the three- month outcome of patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping. Based on this study, there does not appear to be a role for intraoperative cooling for aneurysm clipping. Devin L. Brown, MD Amy C. Mecozzi, BA University of Michigan Medical School Ann Arbor, Michigan REFERENCES 1. Chimowitz MI, Kokkinos J, Strong J, et al. The Warfarin- Aspirin Symptomatic Intracranial Disease Study. Neurology 1995; 45: 1488- 93. 2. Mohr JP, Thompson JL, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. NEnglJ Med 2001; 345: 1444- 51. 3. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Attack Trial. Major Outcomes in high-risk hypertensive patients randomized to angiotensin- converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT). JAMA 2002; 288: 2981- 97. 177 |
