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Kennedy R Lees,
Erich Bluhmki,
Rüdiger von Kummer,
Thomas G Brott,
Danilo Toni,
James C Grotta,
Gregory W Albers,
Markku Kaste,
John R Marler,
Scott A Hamilton, [......],
Jochen Mau,
Dieter Meier, Gregory del Zoppo,
D A De Silva,
K S Butcher,
M W Parsons,
P A Barber,
C Levi,
C Bladin,
G Byrnes
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ABSTRACT: Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis.
We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis.
Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min.
Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit.
None.
The Lancet 05/2010; 375(9727):1695-703. · 38.28 Impact Factor
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Arthur M Pancioli,
Joseph Broderick,
Thomas Brott,
Thomas Tomsick,
Jane Khoury,
Judy Bean, Gregory del Zoppo,
Dawn Kleindorfer,
Daniel Woo,
Pooja Khatri, [......],
James Frey,
James Gebel,
Scott Kasner,
Chelsea Kidwell,
Thomas Kwiatkowski,
Richard Libman,
Richard Mackenzie,
Phillip Scott,
Sidney Starkman,
R Jason Thurman
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ABSTRACT: Multiple approaches are being studied to enhance the rate of thrombolysis for acute ischemic stroke. Treatment of myocardial infarction with a combination of a reduced-dose fibrinolytic agent and a glycoprotein (GP) IIb/IIIa receptor antagonist has been shown to improve the rate of recanalization versus fibrinolysis alone. The combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator (rt-PA) (CLEAR) stroke trial assessed the safety of treating acute ischemic stroke patients within 3 hours of symptom onset with this combination.
The CLEAR trial was a National Institutes of Health/National Institute of Neurological Disorders and Stroke-funded multicenter, double-blind, randomized, dose-escalation and safety study. Patients were randomized 3:1 to either low-dose rt-PA (tier 1=0.3 mg/kg, tier 2=0.45 mg/kg) plus eptifibatide (75 microg/kg bolus followed by 0.75 microg/kg per min infusion for 2 hours) or standard-dose rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracerebral hemorrhage within 36 hours. Secondary analyses were performed regarding clinical efficacy.
Ninety-four patients (40 in tier 1 and 54 in tier 2) were enrolled. The combination group of the 2 dose tiers (n=69) had a median age of 71 years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 14, and the standard-dose rt-PA group (n=25) had a median age of 61 years and a median baseline NIHSS score of 10 (P=0.01 for NIHSS score). Fifty-two (75%) of the combination treatment group and 24 (96%) of the standard treatment group had a baseline modified Rankin scale score of 0 (P=0.04). There was 1 (1.4%; 95% CI, 0% to 4.3%) symptomatic intracranial hemorrhage in the combination group and 2 (8.0%; 95% CI, 0% to 19.2%) in the rt-PA-only arm (P=0.17). During randomization in tier 2, a review by the independent data safety monitoring board demonstrated that the safety profile of combination therapy at the tier 2 doses was such that further enrollment was statistically unlikely to indicate inadequate safety for the combination treatment group, the ultimate outcome of the study. Thus, the study was halted. There was a trend toward increased clinical efficacy of standard-dose rt-PA compared with the combination treatment group.
The safety of the combination of reduced-dose rt-PA plus eptifibatide justifies further dose-ranging trials in acute ischemic stroke.
Stroke 10/2008; 39(12):3268-76. · 5.73 Impact Factor
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Harold P Adams, Gregory del Zoppo,
Mark J Alberts,
Deepak L Bhatt,
Lawrence Brass,
Anthony Furlan,
Robert L Grubb,
Randall T Higashida,
Edward C Jauch,
Chelsea Kidwell,
Patrick D Lyden,
Lewis B Morgenstern,
Adnan I Qureshi,
Robert H Rosenwasser,
Phillip A Scott,
Eelco F M Wijdicks
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ABSTRACT: Our goal is to provide an overview of the current evidence about components of the evaluation and treatment of adults with acute ischemic stroke. The intended audience is physicians and other emergency healthcare providers who treat patients within the first 48 hours after stroke. In addition, information for healthcare policy makers is included.
Members of the panel were appointed by the American Heart Association Stroke Council's Scientific Statement Oversight Committee and represented different areas of expertise. The panel reviewed the relevant literature with an emphasis on reports published since 2003 and used the American Heart Association Stroke Council's Levels of Evidence grading algorithm to rate the evidence and to make recommendations. After approval of the statement by the panel, it underwent peer review and approval by the American Heart Association Science Advisory and Coordinating Committee. It is intended that this guideline be fully updated in 3 years.
Management of patients with acute ischemic stroke remains multifaceted and includes several aspects of care that have not been tested in clinical trials. This statement includes recommendations for management from the first contact by emergency medical services personnel through initial admission to the hospital. Intravenous administration of recombinant tissue plasminogen activator remains the most beneficial proven intervention for emergency treatment of stroke. Several interventions, including intra-arterial administration of thrombolytic agents and mechanical interventions, show promise. Because many of the recommendations are based on limited data, additional research on treatment of acute ischemic stroke is needed.
Circulation 06/2007; 115(20):e478-534. · 14.74 Impact Factor
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ABSTRACT: This workshop examined the opportunities for translational research directed at immune and inflammatory mechanisms. This summary presents the background data in 3 general areas: (1) inflammation and hemostasis in cerebrovascular and cardiovascular disease, (2) immune interactions in the central nervous system and heart, and (3) translation of immune modulation in the brain and heart, all of which supported a consensus derivation of the opportunities for future research in these areas. The summary concludes with 11 recommendations.
Stroke 01/2007; 37(12):3035-42. · 5.73 Impact Factor
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Cheryl D Bushnell,
Patricia Hurn,
Carol Colton,
Virginia M Miller, Gregory del Zoppo,
Mitchell S V Elkind,
Barney Stern,
David Herrington,
Gwendolyn Ford-Lynch,
Philip Gorelick,
Andra James,
Candice M Brown,
Emily Choi,
Paul Bray,
L Kristin Newby,
Larry B Goldstein,
James Simpkins
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ABSTRACT: Women have poorer outcomes from stroke than men. Women also have risk factors that are unique, including pregnancy and hormone therapy. Hormone therapy for postmenopausal replacement increased the risk of ischemic stroke according to results of the Women's Health Initiative clinical trials. Based on the current understanding of the mechanisms of action of estrogen, the reasons for this increased risk are uncertain. One method to better understand the reasons for this increased risk is to re-evaluate estrogen's role in the neurovascular unit, simplistically comprised of the neurons, glia, and endothelial cells, as well as the processes of inflammation, and hemostasis/thrombosis. Besides the role of estrogen there are many gaps of knowledge about issues specific to women and stroke.
A multidisciplinary workshop was held in August 2005 to summarize the current evidence for estrogen and, more generally, stroke in women, and to provide recommendations for future basic, preclinical, and clinical research studies.
These studies may ultimately change the approach to stroke prevention and treatment in women.
Stroke 10/2006; 37(9):2387-99. · 5.73 Impact Factor
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Stroke 05/2005; 36(4):916-23. · 5.73 Impact Factor
