Carotid-artery stenting--case open or closed?
Explore the source record for details and available documents.
Angioplasty↗
Biomedical subjects
Anthony J Furlan
Publications and source records attributed to Anthony J Furlan.
Sex-based differences in the effect of intra-arterial treatment of stroke: analysis of the PROACT-2 study.
BACKGROUND AND PURPOSE: Sex influences outcome after intravenous thrombolysis. In a combined analysis of the tissue plasminogen activator clinical trials, a sex-by-treatment interaction was observed. We sought to confirm that observation in an independent data set. METHODS: Data were from the Pro-Urokinase for Acute Cerebral Thromboembolism-2 (PROACT-2) trial. Baseline factors were compared by sex. The primary outcome was an assessment of a sex-by-treatment interaction term within a logistic regression model, using a modified Rankin Scale score <or=2 at 90 days as the binary outcome. We also assessed whether there were differences in CT-scan appearance and recanalization at 2 hours post-treatment. RESULTS: In the PROACT-2 study of intra-arterial stroke thrombolysis, in both women and men, prourokinase resulted in better outcomes than control. A sex by prourokinase treatment interaction was observed, with women showing a larger treatment effect (20% absolute benefit) compared with men (10% absolute benefit). The reason for this interaction is that thrombolytic treatment nullifies the worse outcome for untreated women compared with men. The reasons for effect modification do not include improved recanalization at 2 hours among women. CONCLUSIONS: Women with middle cerebral artery ischemic stroke benefit more from intra-arterial therapy. Further study of how sex affects stroke outcome is needed.
Aged↗
Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset.
BACKGROUND AND PURPOSE: Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke. METHODS: DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 microg/kg and 125 microg/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined. RESULTS: Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 microg/kg: n=14; 125 microg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 microg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 microg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 microg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 microg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 microg/kg desmoteplase (P=0.022). CONCLUSIONS: Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 microg/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).
Adult↗
IV tissue plasminogen activator for stroke in the community: what we know and don't know 10 years after FDA approval.
Explore the source record for details and available documents.
Drug Approval↗
Multimodal therapy for the treatment of severe ischemic stroke combining GPIIb/IIIa antagonists and angioplasty after failure of thrombolysis.
BACKGROUND AND PURPOSE: Intraarterial and intravenous thrombolysis are often ineffective for the treatment of acute ischemic stroke and are associated with a significant risk of intracranial hemorrhage (ICH). Multimodal rescue therapy combining mechanical disruption and platelet GPIIb/IIIa receptor antagonists may improve recanalization. METHODS: Patients who did not recanalize with thrombolysis were treated with GPIIb/IIIa antagonists, angioplasty, or an embolectomy device. Treatment was individualized based on vascular anatomy, stroke mechanism, patient status, and symptom duration. RESULTS: Twelve patients were treated within 3.8+/-2.2 hours. The mean National Institutes of Health Stroke Scale (NIHSS) score was 19.4+/-4.1. Six patients had carotid terminus occlusion, whereas 5 had middle cerebral artery and 1 had basilar artery occlusion. The average doses of intraarterial tPA and reteplase were 17.1+/-8.6 mg and 2+/-0.6 units, respectively. All patients received either an intravenous or intraarterial abciximab bolus (mean 11.8+/-5.8 mg) and heparin (mean 3278+/-1716U). Eleven were treated with angioplasty and 4 had mechanical embolectomy or stenting. Complete (8) or partial (3) recanalization was achieved in 11 cases. There was only one (8.3%) symptomatic hemorrhage. Patients had a favorable outcome at discharge (mean NIHSS 8.9+/-8.7) and 6 (50%) had an NIHSS < or =4 at discharge. CONCLUSIONS: Multimodal rescue therapy was effective at recanalizing occluded cerebral vessels that failed thrombolysis without an excess risk of ICH.
Aged↗
Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable.
BACKGROUND: Previous Stroke Therapy Academic Industry Roundtable (STAIR) meetings focused on preclinical evidence of drug efficacy and enhancing acute stroke trial design and performance. A fourth (STAIR-IV) was held to discuss relevant issues related to acute stroke drug development and regulatory approval. SUMMARY OF REVIEW: The STAIR-IV meeting had 3 main focus areas. The first topic was novel approaches to statistical design of acute stroke trials and appropriate outcome measures. The second focus was the need for better cooperation among participants in stroke therapy development that may be addressed through a national consortium of stroke trial centers in the United States and elsewhere. Lastly, regulatory issues related to the approval of novel mono and multiple acute stroke therapies were discussed. CONCLUSIONS: The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies.
Brain Ischemia↗
Training, competency, and credentialing standards for diagnostic cervicocerebral angiography, carotid stenting, and cerebrovascular intervention: a joint statement from the American Academy of Neurology, the American Association of Neurological Surgeons, the American Society of Interventional and Therapeutic Neuroradiology, the American Society of Neuroradiology, the Congress of Neurological Surgeons, the AANS/CNS Cerebrovascular Section, and the Society of Interventional Radiology.
Explore the source record for details and available documents.
Angioplasty↗
Devices, drugs, and the Food and Drug Administration: increasing implications for ischemic stroke.
Explore the source record for details and available documents.
Brain Ischemia↗
Quality improvement for stroke management at the Cleveland Clinic Health System.
BACKGROUND: The Cleveland Clinic Health System established a stroke quality improvement (QI) initiative across its nine hospitals. IMPLEMENTING THE STROKE QI INITIATIVE: A stroke QI team took a three-pronged approach to QI: professional education, public education, and hospital process improvements. Its activities and subsequent data analysis needs were divided into four cycles (1999-2003). All data were provided to the stroke QI team and then to the Medical Operations Council to review results, consider data integrity issues, and plan dissemination. The dissemination of performance results permitted broad organizational responses to facilitate improvement. Improvement activities included professional education, public awareness, process improvement, focused data collection with routine feedback, protocol refinement, and coordination of clinical personnel within and between hospitals. RESULTS: The frequency of brain hemorrhagic complications decreased by more than half, from 13.4% to 6.4%; the rate of intravenous tissue plasminogen activator use increased from 1.5% to 3.9% of all stroke patients; and protocol deviations were reduced from 33% to 17%. DISCUSSION: The keys to this initiative's success were the health system's leadership's support, physicians' engagement via multidisciplinary project committees at the health system and hospital levels, and flexibility in implementing locally tailored process interventions.
Humans↗
Training, competency, and credentialing standards for diagnostic cervicocerebral angiography, carotid stenting, and cerebrovascular intervention: a joint statement from the American Academy of Neurology, American Association of Neurological Surgeons, American Society of Interventional and Therapeutic Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, AANS/CNS Cerebrovascular Section, and Society of Interventional Radiology.
Explore the source record for details and available documents.
Carotid Artery Diseases↗
Patent foramen ovale and recurrent stroke: closure is the best option: yes.
Explore the source record for details and available documents.
Anticoagulants↗
Utilization of intravenous tissue plasminogen activator for acute ischemic stroke.
BACKGROUND: Intravenous tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke, although only 2% of patients with stroke receive intravenous tPA nationally. OBJECTIVE: To determine the rate of tPA use for stroke in the Cleveland, Ohio, community and the reasons why patients were excluded from thrombolysis treatment. DESIGN: Retrospective cohort study. SETTING: Community. Subjects Patients admitted because of stroke to the 9 Cleveland Clinic Health System hospitals from June 15, 1999, to June 15, 2000. MAIN OUTCOME MEASURES: Utilization of intravenous tPA and reasons for ineligibility. RESULTS: There were 1923 admissions for ischemic stroke in the 1-year period. Of these, 288 (15.0%) arrived within the 3-hour time window, and approximately 6.9% were considered eligible for tPA. The most common reasons for exclusion among patients arriving within 3 hours were mild neurologic impairment and rapidly improving symptoms. The overall rate of tPA use among patients presenting within 3 hours was 19.4%, and the rate of use among eligible patients was 43.4% (n = 56). The use of tPA did not differ significantly according to race or sex. CONCLUSIONS: Only 15% of patients arrived within the 3-hour time window for intravenous tPA, making delay in presentation the most common reason patients were ineligible for i.v. thrombolysis. Neurologic criteria were the second most common group of exclusions. Overall tPA use was low, but it was used in nearly half of all patients with no documented contraindications. Intravenous tPA use in a community setting can compare favorably with the rate of use seen in academic medical settings.
Age Factors↗
Training, competency, and credentialing standards for diagnostic cervicocerebral angiography, carotid stenting, and cerebrovascular intervention: a joint statement from the American Academy of Neurology, the American Association of Neurological Surgeons, the American Society of Interventional and Therapeutic Neuroradiology, the American Society of Neuroradiology, the Congress of Neurological Surgeons, the AANS/CNS Cerebrovascular Section, and the Society of Interventional Radiology.
Explore the source record for details and available documents.
Carotid Artery Diseases↗
Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke.
BACKGROUND AND PURPOSE: The National Institutes of Health (NIH) estimates that stroke costs now exceed 45 billion dollars per year. Stroke is the third leading cause of death and one of the leading causes of adult disability in North America, Europe, and Asia. A number of well-designed randomized stroke trials and case series have now been reported in the literature to evaluate the safety and efficacy of thrombolytic therapy for the treatment of acute ischemic stroke. These stroke trials have included intravenous studies, intra-arterial studies, and combinations of both, as well as use of mechanical devices for removal of thromboemboli and of neuroprotectant drugs, alone or in combination with thrombolytic therapy. At this time, the only therapy demonstrated to improve outcomes from an acute stroke is thrombolysis of the clot responsible for the ischemic event. There is room for improvement in stroke lysis studies. Divergent criteria, with disparate reporting standards and definitions, have made direct comparisons between stroke trials difficult to compare and contrast in terms of overall patient outcomes and efficacy of treatment. There is a need for more uniform definitions of multiple variables such as collateral flow, degree of recanalization, assessment of perfusion, and infarct size. In addition, there are multiple unanswered questions that require further investigation, in particular, questions as to which patients are best treated with thrombolysis. One of the most important predictors of clinical success is time to treatment, with early treatment of <3 hours for intravenous tissue plasminogen activator and <6 hours for intra-arterial thrombolysis demonstrating significant improvement in terms of 90-day clinical outcome and reduced cerebral hemorrhage. It is possible that improved imaging that identifies the ischemic penumbra and distinguishes it from irreversibly infarcted tissue will more accurately select patients for therapy than duration of symptoms. There are additional problems in the assessment of patients eligible for thrombolysis. These include being able to predict whether a particular site of occlusion can be successfully revascularized, predict an individual patient's prognosis and outcome after revascularization, and in particular, to predict the development of intracerebral hemorrhage, with and without clinical deterioration. It is not clear to assume that achieving immediate flow restoration due to thrombolytic therapy implies clinical success and improved outcome. There is no simple correlation between recanalization and observed clinical benefit in all ischemic stroke patients, because other interactive variables, such as collateral circulation, the ischemic penumbra, lesion location and extent, time to treatment, and hemorrhagic conversion, are all interrelated to outcome. METHODS: This article was written under the auspices of the Technology Assessment Committees for both the American Society of Interventional and Therapeutic Neuroradiology and the Society of Interventional Radiology. The purpose of this document is to provide guidance for the ongoing study design of trials of intra-arterial cerebral thrombolysis in acute ischemic stroke. It serves as a background for the intra-arterial thrombolytic trials in North America and Europe, discusses limitations of thrombolytic therapy, defines predictors for success, and offers the rationale for the different considerations that might be important during the design of a clinical trial for intra-arterial thrombolysis in acute stroke. Included in this guidance document are suggestions for uniform reporting standards for such trials. These definitions and standards are mainly intended for research trials; however, they should also be helpful in clinical practice and applicable to all publications. This article serves to standardize reporting terminology and includes pretreatment assessment, neurologic evaluation with the NIH Stroke Scale score, imaging evaluation, occlusion sites, perfusion grades, follow-up imaging studies, and neurologic assessments. Moreover, previously used and established definitions for patient selection, outcome assessment, and data analysis are provided, with some possible variations on specific end points. This document is therefore targeted to help an investigator to critically review the scales and scores used previously in stroke trials. This article also seeks to standardize patient selection for treatment based on neurologic condition at presentation, baseline imaging studies, and utilization of standardized inclusion/exclusion criteria. It defines outcomes from therapy in phase I, II, and III studies. Statistical approaches are presented for analyzing outcomes from prospective, randomized trials with both primary and secondary variable analysis. A discussion on techniques for angiography, intra-arterial thrombolysis, anticoagulation, adjuvant therapy, and patient management after therapy is given, as well as recommendations for posttreatment evaluation, duration of follow-up, and reporting of disability outcomes. Imaging assessment before and after treatment is given. In the past, noncontrast CT brain scans were used as the initial screening examination of choice to exclude cerebral hemorrhage. However, it is now possible to quantify the volume of early infarct by using contiguous, discrete (nonhelical) images of 5 mm. In addition, CT angiography by helical scanning and 100 mL of intravenous contrast agent can be used expeditiously to obtain excellent vascular anatomy, define the occlusion site, obtain 2D and 3D reformatted vascular images, grade collateral blood flow, and perform tissue-perfusion studies to define transit times of a contrast bolus through specific tissue beds and regions of interest in the brain. Dynamic CT perfusion scans to assess the whole dynamics of a contrast agent transit curve can now be routinely obtained at many hospitals involved in these studies. The rationale, current status of this technology, and potential use in future clinical trials are given. Many hospitals are also performing MR brain studies at baseline in addition to, or instead of, CT scans. MRI has a high sensitivity and specificity for the diagnosis of ischemic stroke in the first several hours from symptom onset, identifies arterial occlusions, and characterizes ischemic pathology noninvasively. Case series have demonstrated and characterized the early detection of intraparenchymal hemorrhage and subarachnoid hemorrhage by MRI. Echo planar images, used for diffusion MRI and, in particular, perfusion MRI are inherently sensitive for the susceptibility changes caused by intraparenchymal blood products. Consequently, MRI has replaced CT to rule out acute hemorrhage in some centers. The rationale and the potential uses of MR scanning are provided. In addition to established criteria, technology is continuously evolving, and imaging techniques have been introduced that offer new insights into the pathophysiology of acute ischemic stroke. For example, a better patient stratification might be possible if CT and/or MRI brain scans are used not only as exclusion criteria but also to provide individual inclusion and exclusion criteria based on tissue physiology. Imaging techniques might also be used as a surrogate outcome measure in future thrombolytic trials. The context of a controlled study is the best environment to validate emerging imaging and treatment techniques. The final section details reporting standards for complications and adverse outcomes; defines serious adverse events, adverse events, and unanticipated adverse events; and describes severity of complications and their relation to treatment groups. Recommendations are made regarding comparing treatment groups, randomization and blinding, intention-to-treat analysis, quality-of-life analysis, and efficacy analysis. This document concludes with an analysis of general costs associated with therapy, a discussion regarding entry criteria, outcome measures, and the variability of assessment of the different stroke scales currently used in the literature is also featured. CONCLUSIONS: In summary, this article serves to provide a more uniform set of criteria for clinical trials and reporting outcomes used in designing stroke trials involving intra-arterial thrombolytic agents, either alone or in combination with other therapies. It is anticipated that by having a more uniform set of reporting standards, more meaningful analysis of the data and the literature will be able to be achieved.
Acute Disease↗
Factors influencing outcome and treatment effect in PROACT II.
BACKGROUND AND PURPOSE: The PROACT II study demonstrated a significant benefit from treatment with intra-arterial pro-urokinase (r-proUK) in patients with middle cerebral artery occlusion treated within 6 hours of stroke onset. The purpose of the current study was to examine baseline factors to determine predictors of good outcome and response to treatment. METHODS: We selected from the baseline clinical, radiologic, and angiographic data variables that considered possibly related to outcome. A univariate analysis was performed to examine the association between these baseline factors and good outcome, defined as a modified Rankin scale score <or=2. A multivariate model then selected the most important variables independently influencing prognosis. A risk score for each patient was constructed on the basis of the patient's individual values for each independent variable. Patients were stratified into risk quartiles based on their risk scores, and an odds ratio for each risk quartile was calculated. The treatment effects of each quartile were compared. RESULTS: In the univariate analysis, screening National Institutes of Health stroke scale (NIHSS) score and age were strongly associated with good outcome. The multivariate model selected age, NIHSS score, and CT hypodensity as the most important prognostic variables. Dividing patients into quartiles based on risk scores achieved a uniform gradient of probability of good outcomes. A trend toward benefit of r-proUK treatment was seen in all risk quartiles, and no differential treatment effect was observed across risk groups. CONCLUSIONS: There was no evidence of differential effect of r-proUK across subgroups of patients stratified by risk.
Adult↗
Cuyahoga County Operation Stroke speed of emergency department evaluation and compliance with National Institutes of Neurological Disorders and Stroke time targets.
BACKGROUND AND PURPOSE: Although the National Institutes of Neurological Disorders and Stroke (NINDS) has established time targets for the evaluation of acute stroke patients, little is known about how often these targets are met in the community. To track compliance with NINDS guidelines, Cuyahoga County Operation Stroke implemented a countywide data collection process that provides comparative reporting of hospital performance. METHODS: Data on the emergency department evaluation of stroke patients have been retrospectively collected since January 2000 by hospitals participating in Cuyahoga County Operation Stroke. All hospitals used a 1-page form that includes NINDS time target information. RESULTS: Median time to emergency department arrival for the 1003 patients in this cohort was 115 minutes; 382 patients (38%) arrived in <3 hours; 506 (50%) arrived in <6 hours. After arrival, median time to physician contact was 12 minutes, time to CT was 65 minutes, and time to imaging results was 105 minutes. Earlier arrival intervals after symptom onset were independently associated with shorter evaluation times. All time targets were met in patients receiving intravenous tissue plasminogen activator. CONCLUSIONS: A countywide data collection system for acute stroke evaluation is feasible. In the Cleveland metropolitan area, time to physician contact is close to the recommended NINDS target. Time to CT and time to imaging results are substantially longer than recommended. However, there was wide variation between hospitals. The association between time to arrival, speed of evaluation, and administration of intravenous tissue plasminogen activator suggests that community physicians selectively accelerate the evaluation and management of potential thrombolysis candidates.
Aged↗
Quality improvement and tissue-type plasminogen activator for acute ischemic stroke: a Cleveland update.
BACKGROUND AND PURPOSE: A systematic audit of intravenous tissue-type plasminogen activator (tPA) use and stroke outcomes in Cleveland, Ohio, during 1997-1998 demonstrated higher rates of symptomatic intracranial hemorrhage (ICH) than reported in the National Institute of Neurological Disorders and Stroke (NINDS) trial. We now report updated results of intravenous tPA use in the Cleveland Clinic Health System (CCHS). METHODS: A stroke quality improvement program was initiated in the 9-hospital CCHS in 1999. A retrospective chart review for all stroke patients with primary International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes 434 and 436 admitted to the 9 hospitals from June 1999 to June 2000 was used to determine outcomes of patients treated with intravenous tPA. RESULTS: Intravenous tPA was given to 18.8% of patients arriving within 3 hours of symptom onset. Protocol deviations occurred in 19.1% of patients given intravenous tPA. The symptomatic ICH rate was 6.4%. CONCLUSIONS: Since 1997, intravenous tPA use has increased, while the rates of symptomatic ICH and protocol deviations have decreased in the CCHS. The CCHS symptomatic ICH rate is now similar to that reported in the NINDS trial. These improvements occurred after initiation of a stroke quality improvement program.
Acute Disease↗