Showing papers by "Werner Hacke published in 2007"

Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials

Abstract: Summary Background Malignant infarction of the middle cerebral artery (MCA) is associated with an 80% mortality rate. Non-randomised studies have suggested that decompressive surgery reduces this mortality without increasing the number of severely disabled survivors. To obtain sufficient data as soon as possible to reliably estimate the effects of decompressive surgery, results from three European randomised controlled trials (DECIMAL, DESTINY, HAMLET) were pooled. The trials were ongoing when the pooled analysis was planned. Methods Individual data for patients aged between 18 years and 60 years, with space-occupying MCA infarction, included in one of the three trials, and treated within 48 h after stroke onset were pooled for analysis. The protocol was designed prospectively when the trials were still recruiting patients and outcomes were defined without knowledge of the results of the individual trials. The primary outcome measure was the score on the modified Rankin scale (mRS) at 1 year dichotomised between favourable (0–4) and unfavourable (5 and death) outcome. Secondary outcome measures included case fatality rate at 1 year and a dichotomisation of the mRS between 0–3 and 4 to death. Data analysis was done by an independent data monitoring committee. Findings 93 patients were included in the pooled analysis. More patients in the decompressive-surgery group than in the control group had an mRS≤4 (75% vs 24%; pooled absolute risk reduction 51% [95% CI 34–69]), an mRS≤3 (43% vs 21%; 23% [5–41]), and survived (78% vs 29%; 50% [33–67]), indicating numbers needed to treat of two for survival with mRS≤4, four for survival with mRS≤3, and two for survival irrespective of functional outcome. The effect of surgery was highly consistent across the three trials. Interpretation In patients with malignant MCA infarction, decompressive surgery undertaken within 48 h of stroke onset reduces mortality and increases the number of patients with a favourable functional outcome. The decision to perform decompressive surgery should, however, be made on an individual basis in every patient.

Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY). A Randomized, Controlled Trial

Abstract: Background and Purpose— Decompressive surgery (hemicraniectomy) for life-threatening massive cerebral infarction represents a controversial issue in neurocritical care medicine. We report here the 30-day mortality and 6- and 12-month functional outcomes from the DESTINY trial. Methods— DESTINY (ISRCTN01258591) is a prospective, multicenter, randomized, controlled, clinical trial based on a sequential design that used mortality after 30 days as the first end point. When this end point was reached, patient enrollment was interrupted as per protocol until recalculation of the projected sample size was performed on the basis of the 6-month outcome (primary end point=modified Rankin Scale score, dichotomized to 0 to 3 versus 4 to 6). All analyses were based on intention to treat. Results— A statistically significant reduction in mortality was reached after 32 patients had been included: 15 of 17 (88%) patients randomized to hemicraniectomy versus 7 of 15 (47%) patients randomized to conservative therapy surviv...

Predictors of Early Cardiac Morbidity and Mortality After Ischemic Stroke

Abstract: Background and Purpose— In the first 3 months after acute ischemic stroke, 2% to 6% of patients die from cardiac causes. This may reflect preexisting cardiac disease, cardiac dysfunction related to the acute neurohumoral and autonomic stress response to stroke, or both. Delineation of a high-risk group could facilitate prevention strategies. We aimed to describe the temporal profile of cardiac risk after stroke and develop a predictive model of serious cardiac adverse events (SCAEs) using baseline variables. Methods— We used data from the one trial in the Virtual International Stroke Trials Archive that matched prespecified criteria. Survival analysis was used to describe the temporal profile of cardiac events after stroke. Prognostic determinants were assessed with multivariable logistic regression, and a risk score was derived from the key predictor variables. Results— Of 846 ischemic stroke patients, 35 (4.1%) died from cardiac causes and 161 (19.0%) suffered at least one SCAE. The hazard of cardiac de...

Facilities Available in European Hospitals Treating Stroke Patients

Abstract: Background and Purpose— Stroke units decrease mortality and need for institutional care, but they are not widely available. The objective of the study was to determine, among European hospitals admitting acute stroke patients, how many are able to provide an appropriate level of care. Method— We randomly selected 886 hospitals in 25 countries. We used definitions derived from a European expert survey for comprehensive stroke centers (CSC), primary stroke centers (PSC), and minimum level required for any hospital ward (AHW) admitting stroke patients. We determined the proportion of hospitals meeting criteria for each category, and which facilities were not available. Results— Participating hospitals treated approximately one-third of all strokes supposed to have occurred in these countries in 2005. Forty-three (4.9%) met criteria for CSC, 32 (3.6%) for PSC, 356 (40.2%) for AHW, and 455 (51.4%) provided a lower level of care. In 2005, hospitals meeting criteria for CSC, PSC, AHW, and none of them admitted 2...

The virtual international stroke trials archive

Abstract: Background and Purpose - Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses. Methods - Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing. Results - ”Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on 15 000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 6912 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials. Conclusions - This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning. (Stroke. 2007;38:1905-1910.)

Shift Analysis Versus Dichotomization of the Modified Rankin Scale Outcome Scores in the NINDS and ECASS-II Trials

Abstract: Background and Purpose— The SAINT I trial that showed a significant benefit of the neuroprotectant NXY-059 used a novel outcome for acute ischemic stroke trials: a shift toward good functional outcome on the 7-category modified Rankin scale (mRS). Methods— We used the Cochran-Mantel-Haenszel shift test to analyze the distribution of the 90-day mRS outcomes in the NINDS and ECASS-II databases and compared the results with a dichotomized mRS outcome by logistic regression (0 to 2 vs 3 to 6, or 0 to 1 vs 2 to 6). We also stratified each dataset based on National Institutes of Health Stroke Scale baseline severity. Results— Each dataset showed a statistically significant shift in the 90-day mRS distributions favoring tissue plasminogen activator (odds ratio, 1.6 for NINDS, 1.3 for ECASS-II). For ECASS-II, larger shift effects appeared in National Institutes of Health Stroke Scale 0 to 6 and 16 to 40 strata. Similarly, the mRS 0 to 2 analysis but not mRS 0 to 1 found similar treatment effects in both datasets ...

The main components of stroke unit care: results of a European expert survey.

Abstract: Background and Purpose: Stroke units decrease mortality, handicap and need for institutional care, but there are only sparse evidence-based data showing which components make the difference over general wards. The aim of this survey was to identify from expert opinions what should be the major components of stroke units. Methods: A questionnaire was sent to 83 European stroke experts, to ask their opinion on what should be the components of comprehensive stroke centres (CSC), primary stroke centres (PSC) and any hospital ward (AHW) admitting acute stroke patients routinely. It consisted of a list of 107 components (personnel, diagnostic procedures, monitoring, invasive treatments provided, infrastructures, protocols and procedures and their availability for 24 h a day for 7 days a week, 24/7) to be classified as irrelevant, useful but not necessary, desirable, important but not absolutely necessary, or absolutely necessary. Results: 42 questionnaires (50.6%) were returned. Four components were excluded because of a poor level of agreement between experts. Eight components were considered as absolutely necessary by more than 75% of the experts for both CSC and PSC: multidisciplinary team, stroke-trained nurses, brain CT scan 24/7, CT priority for stroke patients, extracranial Doppler sonography, automated electrocardiographic monitoring, intravenous rt-PA protocols 24/7 and in-house emergency department. Eleven other components (in the fields of vascular surgery, neurosurgery, interventional radiology and clinical research) were considered as necessary in CSC by more than 75% of the experts. Only 8 components were considered as important but not absolutely necessary by more than 50% of the experts for AHW. Conclusion: The experts showed a high level of agreement about the essential components of organized acute stroke care, providing useful information to health authorities for the allocation of resources.

An analysis of mortality rates with dual-antiplatelet therapy in the primary prevention population of the CHARISMA trial

Abstract: Aims To examine the unanticipated, excess mortality observed in patients randomized to clopidogrel and aspirin vs. aspirin alone in the prespecified ‘asymptomatic’ subgroup of CHARISMA, we investigated whether dual-antiplatelet therapy may be associated with adverse cardiovascular (CV) events in a primary prevention population. Methods and results Of 15 603 patients enrolled, 3284 were initially categorized as asymptomatic with CV risk factors, but 995 had a prior CV event, leaving 2289 patients to represent the primary prevention cohort. This subset was compared with 13 148 symptomatic patients with established vascular disease and both were evaluated for CV death and bleeding. A multivariate analysis analysed predictors of CV death in this group. No post mortem data were available. Compared with aspirin alone, a significant increase in CV death (P ¼ 0.01) was observed in patients receiving dual-antiplatelet therapy in the asymptomatic population. Within the primary prevention cohort, this excess CV death was not significant (P ¼ 0.07). Multivariate analysis of the primary prevention group showed a trend towards excess CV death (P ¼ 0.054; HR 1.72; CI 0.99–2.97) with dual-antiplatelet therapy (aspirin plus clopidogrel). Other independent predictors of CV death included increasing age, hypertension, atrial fibrillation, and a history of heart failure. There was a non-significant increase in moderate or severe bleeding (P ¼ 0.218) with dual-antiplatelet therapy; thus, bleeding was an unlikely explanation for the excess event rate. Conclusion These findings do not support the use of dual-antiplatelet therapy with clopidogrel and aspirin in a primary prevention population. In this subgroup analysis, CV death occurred more frequently than anticipated. The cause of this apparent harm is not elucidated, may represent play of chance, but requires further prospective evaluation.

Clinical review: Therapy for refractory intracranial hypertension in ischaemic stroke.

Abstract: The treatment of patients with large hemispheric ischaemic stroke accompanied by massive space-occupying oedema represents one of the major unsolved problems in neurocritical care medicine. Despite maximum intensive care, the prognosis of these patients is poor, with case fatality rates as high as 80%. Therefore, the term 'malignant brain infarction' was coined. Because conservative treatment strategies to limit brain tissue shift almost consistently fail, these massive infarctions often are regarded as an untreatable disease. The introduction of decompressive surgery (hemicraniectomy) has completely changed this point of view, suggesting that mortality rates may be reduced to approximately 20%. However, critics have always argued that the reduction in mortality may be outweighed by an accompanying increase in severe disability. Due to the lack of conclusive evidence of efficacy from randomised trials, controversy over the benefit of these treatment strategies remained, leading to large regional differences in the application of this procedure. Meanwhile, data from randomised trials confirm the results of former observational studies, demonstrating that hemicraniectomy not only significantly reduces mortality but also significantly improves clinical outcome without increasing the number of completely dependent patients. Hypothermia is another promising treatment option but still needs evidence of efficacy from randomised controlled trials before it may be recommended for clinical routine use. This review gives the reader an integrated view of the current status of treatment options in massive hemispheric brain infarction, based on the available data of clinical trials, including the most recent data from randomised trials published in 2007.

Stenting for carotid artery stenosis.

Abstract: Stenting is being used increasingly for the treatment of carotid artery stenosis, but it is still unknown whether it is as safe and successful as carotid endarterectomy—the standard treatment for symptomatic patients with more than 50% carotid stenosis. This Review summarizes current knowledge on the effectiveness of both procedures, and provides an updated meta-analysis based on data from randomized trials.

Thrombolysis with alteplase for acute ischemic stroke: review of SITS-MOST and other Phase IV studies

Abstract: Thrombolytic therapy is the only approved therapy for acute ischemic stroke patients. As part of the European approval process, the Safe Implementation of Thrombolysis in Stroke - Monitoring Study (SITS-MOST) was demanded as a Phase IV study to evaluate the safety and efficacy of alteplase in a 3-h time-window. This article summarizes SITS-MOST and compares it with other Phase IV studies. Between 2002 and 2006, 6483 patients were included in 285 centers; median age was 68 years, median National Institutes of Health Stroke Scale (NIHSS) score was 12 and the median time-window was 140 min. The rate of symptomatic intracerebral hemorrhages, defined as parenchymal hemorrhage type 2 combined with a neurological deterioration of at least 4 points on NIHSS, was 1.7% within 24 h after treatment. Symptomatic hemorrhages as defined by the National Institute of Neurological and Communicative Disorders and Stroke criteria occurred in 7.3% of patients. The 3-month mortality was 11.3% and the rate of good clinical outcome (modified Rankin Score 0-2) was 55%. There were no major differences between experienced and inexperienced centers regarding safety or efficacy. The results of SITS-MOST are comparable with the results of the randomized placebo-controlled trials and other Phase IV studies such as standard treatment with Alteplase to Reverse Stroke and Canadian Alteplase for Stroke Effectiveness Study. They confirm that intravenous alteplase is safe and effective in routine clinical practice when used for acute stroke within 3 h of stroke onset, even in centers with little previous experience of thrombolytic therapy but only if the licensing approval criteria are strictly followed. These findings should encourage wider use of thrombolytic therapies for suitable stroke patients treated in stroke centers.

Systemic Reperfusion Therapy in Acute Ischemic Stroke

Abstract: Introduction: Experimental and clinical studies indicate that early reperfusion of occluded brain-supplying arteries reduces the size of injury and improves outcome. Recombinant tis