W Hacke

University of Toronto, Toronto, Ontario, Canada

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Publications (626)2863.47 Total impact

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    ABSTRACT: Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation.
    European heart journal. 09/2014;
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    ABSTRACT: We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial.
    European heart journal. 08/2014;
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    ABSTRACT: Background Alteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase. Methods We did a pre-specified meta-analysis of individual patient data from 6756 patients in nine randomised trials comparing alteplase with placebo or open control. We included all completed randomised phase 3 trials of intravenous alteplase for treatment of acute ischaemic stroke for which data were available. Retrospective checks confirmed that no eligible trials had been omitted. We defined a good stroke outcome as no significant disability at 3–6 months, defined by a modified Rankin Score of 0 or 1. Additional outcomes included symptomatic intracranial haemorrhage (defined by type 2 parenchymal haemorrhage within 7 days and, separately, by the SITS-MOST definition of parenchymal type 2 haemorrhage within 36 h), fatal intracranial haemorrhage within 7 days, and 90-day mortality. Findings Alteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 3·0 h resulted in a good outcome for 259 (32·9%) of 787 patients who received alteplase versus 176 (23·1%) of 762 who received control (OR 1·75, 95% CI 1·35–2·27); delay of greater than 3·0 h, up to 4·5 h, resulted in good outcome for 485 (35·3%) of 1375 versus 432 (30·1%) of 1437 (OR 1·26, 95% CI 1·05–1·51); and delay of more than 4·5 h resulted in good outcome for 401 (32·6%) of 1229 versus 357 (30·6%) of 1166 (OR 1·15, 95% CI 0·95–1·40). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial haemorrhage (type 2 parenchymal haemorrhage definition 231 [6·8%] of 3391 vs 44 [1·3%] of 3365, OR 5·55, 95% CI 4·01–7·70, p<0·0001; SITS-MOST definition 124 [3·7%] vs 19 [0·6%], OR 6·67, 95% CI 4·11–10·84, p<0·0001) and of fatal intracranial haemorrhage within 7 days (91 [2·7%] vs 13 [0·4%]; OR 7·14, 95% CI 3·98–12·79, p<0·0001). The relative increase in fatal intracranial haemorrhage from alteplase was similar irrespective of treatment delay, age, or stroke severity, but the absolute excess risk attributable to alteplase was bigger among patients who had more severe strokes. There was no excess in other early causes of death and no significant effect on later causes of death. Consequently, mortality at 90 days was 608 (17·9%) in the alteplase group versus 556 (16·5%) in the control group (hazard ratio 1·11, 95% CI 0·99–1·25, p=0·07). Taken together, therefore, despite an average absolute increased risk of early death from intracranial haemorrhage of about 2%, by 3–6 months this risk was offset by an average absolute increase in disability-free survival of about 10% for patients treated within 3·0 h and about 5% for patients treated after 3·0 h, up to 4·5 h. Interpretation Irrespective of age or stroke severity, and despite an increased risk of fatal intracranial haemorrhage during the first few days after treatment, alteplase significantly improves the overall odds of a good stroke outcome when delivered within 4·5 h of stroke onset, with earlier treatment associated with bigger proportional benefits. Funding UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.
    Lancet. 08/2014;
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    ABSTRACT: We are entering a challenging but exciting period when many new interventions may appear for stroke based on the use of devices. Hopefully these will lead to improved outcomes at a cost that can be afforded in most parts of the world. Nevertheless, it is vital that lessons are learnt from failures in the development of pharmacological interventions (and from some early device studies), including inadequate preclinical testing, suboptimal trial design and analysis, and underpowered studies. The device industry is far more disparate than that seen for pharmaceuticals; companies are very variable in size and experience in stroke, and are developing interventions across a wide range of stroke treatment and prevention. It is vital that companies work together where sales and marketing are not involved, including in understanding basic stroke mechanisms, prospective systematic reviews, and education of physicians. Where possible, industry and academics should also work closely together to ensure trials are designed to be relevant to patient care and outcomes. Additionally, regulation of the device industry lags behind that for pharmaceuticals, and it is critical that new interventions are shown to be safe and effective rather than just feasible. Phase IV postmarketing surveillance studies will also be needed to ensure that devices are safe when used in the ‘real-world’ and to pick up uncommon adverse events.
    International Journal of Stroke 08/2014; 9(6). · 2.75 Impact Factor
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    ABSTRACT: -Nonvalvular atrial fibrillation (AF) is common in elderly patients, who face an elevated risk of stroke but difficulty sustaining warfarin treatment. The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the ROCKET AF trial. This prespecified secondary analysis compares outcomes in older and younger patients.
    Circulation 06/2014; · 15.20 Impact Factor
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    ABSTRACT: Each year, 1·0–2·0% of individuals with atrial fibrillation and 0·1–0·2% of those with venous thromboembolism who are receiving one of the novel oral anticoagulants (dabigatran, rivaroxaban, or apixaban) can be expected to experience an acute ischemic stroke. Additionally, 0·2–0·5% of individuals with atrial fibrillation who are receiving one of the novel oral anticoagulants can be expected to experience an intracranial hemorrhage. This opinion piece addresses the current literature and offers practical approaches to the management of patients receiving novel oral anticoagulants who present with an ischemic or hemorrhagic stroke. Specifically, we discuss the role of thrombolysis in anticoagulated patients with acute ischemic stroke and factors to consider concerning restarting anticoagulation after acute ischemic and hemorrhagic stroke.
    International Journal of Stroke 06/2014; · 2.75 Impact Factor
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    ABSTRACT: Antiarrhythmic drugs (AADs) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. To study the use and outcomes of AAD therapy in anticoagulated patients with AF. Patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial (N = 14,264) were stratified by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across AAD groups as well as across treatment assignment (rivaroxaban or warfarin). Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone and 537 [3.8%] with other AADs). Amiodarone-treated patients were less often female (38% vs 48%), had more persistent AF (64% vs 40%), and more concomitant heart failure (71% vs 41%) than were patients receiving other AADs. Patients receiving no AAD more closely resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone than in those receiving no AAD (50% vs 58%; P < .0001). Compared with no AAD, neither amiodarone (adjusted hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.74-1.31; P = .9) nor other AADs (adjusted HR 0.66; 95% CI 0.37-1.17; P = .15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Treatment effects of rivaroxaban vs warfarin in patients receiving no AAD were consistent with results from the overall trial (primary end point: adjusted HR 0.82; 95% CI 0.68-0.98; Pinteraction = .06; safety end point: adjusted HR 1.12; 95% CI 0.90-1.24; Pinteraction = .33). Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The effect of amiodarone on outcomes in patients receiving rivaroxaban requires further investigation.
    Heart rhythm: the official journal of the Heart Rhythm Society 05/2014; · 4.56 Impact Factor
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    ABSTRACT: In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk. Because of differences in patient demographics, epidemiology, and stroke risk management in East Asia, outcomes and relative effects of rivaroxaban versus warfarin were assessed to determine consistency among East Asians versus other ROCKET AF participants. Baseline demographics and interaction of treatment effects of rivaroxaban and warfarin among patients within East Asia and outside were assessed. A total of 932 (6.5%) ROCKET AF participants resided in East Asia. At baseline, East Asians had lower weight, creatinine clearance, and prior vitamin K antagonist use; higher prevalence of prior stroke; and less congestive heart failure and prior myocardial infarction than other participants. Despite higher absolute event rates for efficacy and safety outcomes in East Asians, the relative efficacy of rivaroxaban (20 mg once daily; 15 mg once daily for creatinine clearance of 30-49 mL/min) versus warfarin with respect to the primary efficacy end point (stroke/systemic embolism) was consistent among East Asians and non-East Asians (interaction P=0.666). Relative event rates for the major or nonmajor clinically relevant bleeding in patients treated with rivaroxaban and warfarin were consistent among East Asians and non-East Asians (interaction P=0.867). Observed relative efficacy and safety of rivaroxaban versus warfarin were similar among patients within and outside East Asia. Rivaroxaban, 20 mg once daily, is an alternative to warfarin for stroke prevention in East Asians with nonvalvular atrial fibrillation. http://www.clinicaltrials.gov. Unique identifier: NCT00123456.
    Stroke 04/2014; · 6.16 Impact Factor
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    ABSTRACT: Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation. We investigated the rate, outcomes, and predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Cox proportional hazards modeling was used. During 1.94 years (median) of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67% per year. The significant, independent predictors of ICH were race (Asian: hazard ratio, 2.02; 95% CI, 1.39-2.94; black: hazard ratio, 3.25; 95% CI, 1.43-7.41), age (1.35; 1.13-1.63 per 10-year increase), reduced serum albumin (1.39; 1.12-1.73 per 0.5 g/dL decrease), reduced platelet count below 210×10(9)/L (1.08; 1.02-1.13 per 10×10(9)/L decrease), previous stroke or transient ischemic attack (1.42; 1.02-1.96), and increased diastolic blood pressure (1.17; 1.01-1.36 per 10 mm Hg increase). Predictors of a reduced risk of ICH were randomization to rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47-0.89). The ability of the model to discriminate individuals with and without ICH was good (C-index, 0.69; 95% CI, 0.64-0.73). Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations.
    Stroke 04/2014; · 6.16 Impact Factor
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    ABSTRACT: There are no data regarding management and outcomes of major bleeding events in patients treated with oral factor Xa inhibitors. Using data from ROCKET AF, we analysed the management and outcomes of major bleeding overall and according to the randomized treatment. During a median follow-up of 1.9 years, 779 (5.5%) patients experienced major bleeding at a rate of 113.2 events/100 patient-years with a similar event rate in each arm (n = 395 rivaroxaban vs. n = 384 warfarin). The median number of transfused packed red blood cells (PRBC) per episode was similar in both arms [2 (25th, 75th: 2, 4) units]. Overall, few transfusions of whole blood (n = 14), platelets (n = 10), or cryoprecipitate (n = 2) were used. Transfusion of fresh frozen plasma (FFP) was significantly less in the rivaroxaban arm (n = 45 vs. n = 81 units) after adjustment for covariates [odds ratio (OR) 0.43 (95% CI 0.29-0.66); P < 0.0001]. Prothrombin complex concentrates (PCC) were administered less in the rivaroxaban arm (n = 4 vs. n = 9). Outcomes after major bleeding, including stroke or non-central nervous system embolism (4.7% rivaroxaban vs. 5.4% warfarin; HR 0.89; 95% CI 0.42-1.88) and all-cause death (20.4% rivaroxaban vs. 26.1% warfarin; HR 0.69, 95% CI 0.46-1.04) were similar in patients treated with rivaroxaban and warfarin (interaction P = 0.51 and 0.11). Among high-risk patients with atrial fibrillation who experienced major bleeding in ROCKET AF, the use of FFP and PCC was less among those allocated rivaroxaban compared with warfarin. However, use of PRBCs and outcomes after bleeding were similar among patients randomized to rivaroxaban or to warfarin.
    European Heart Journal 04/2014; · 14.10 Impact Factor
  • International Journal of Stroke 04/2014; 9(3):E12-3. · 2.75 Impact Factor
  • Der Nervenarzt 04/2014; 85(4):477. · 0.80 Impact Factor
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    ABSTRACT: Early decompressive hemicraniectomy reduces mortality without increasing the risk of very severe disability among patients 60 years of age or younger with complete or subtotal space-occupying middle-cerebral-artery infarction. Its benefit in older patients is uncertain. We randomly assigned 112 patients 61 years of age or older (median, 70 years; range, 61 to 82) with malignant middle-cerebral-artery infarction to either conservative treatment in the intensive care unit (the control group) or hemicraniectomy (the hemicraniectomy group); assignments were made within 48 hours after the onset of symptoms. The primary end point was survival without severe disability (defined by a score of 0 to 4 on the modified Rankin scale, which ranges from 0 [no symptoms] to 6 [death]) 6 months after randomization. Hemicraniectomy improved the primary outcome; the proportion of patients who survived without severe disability was 38% in the hemicraniectomy group, as compared with 18% in the control group (odds ratio, 2.91; 95% confidence interval, 1.06 to 7.49; P=0.04). This difference resulted from lower mortality in the surgery group (33% vs. 70%). No patients had a modified Rankin scale score of 0 to 2 (survival with no disability or slight disability); 7% of patients in the surgery group and 3% of patients in the control group had a score of 3 (moderate disability); 32% and 15%, respectively, had a score of 4 (moderately severe disability [requirement for assistance with most bodily needs]); and 28% and 13%, respectively, had a score of 5 (severe disability). Infections were more frequent in the hemicraniectomy group, and herniation was more frequent in the control group. Hemicraniectomy increased survival without severe disability among patients 61 years of age or older with a malignant middle-cerebral-artery infarction. The majority of survivors required assistance with most bodily needs. (Funded by the Deutsche Forschungsgemeinschaft; DESTINY II Current Controlled Trials number, ISRCTN21702227.).
    New England Journal of Medicine 03/2014; 370(12):1091-100. · 51.66 Impact Factor
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    ABSTRACT: Thrombosis of cerebral veins or sinuses (CVST) is a rare condition. In a monocentric retrospective cohort study the clinical characteristics, risk factors, radiological findings as well as course and prognosis of patients over the past 15 years were examined. Between January 1998 and March 2013 all patients who were treated as inpatients for CVST at the department of neurology of the University of Heidelberg were systematically registered in a database. Along with all relevant clinical data the modified Rankin scale (MRS) was used to measure the clinical severity. A follow-up visit was performed at three time points. The odds ratios (OR) were calculated to establish predictors of good outcome (MRS 0-2), mortality at discharge and at follow-up. Significant variables after univariate analysis were tested for independency in a multivariate logistic regression model. A total of 143 patients were included in the study. The median age was 43 years (range 17-74 years) and 67.4 % of patients were female. The most common symptoms were headache (70.6 %), seizures (50.4 %) and paresis (37.8 %). The most prominent clinical risk factor was oral contraception (40.4 %). The two most common localizations of thrombosis were the transversal sinus with the sigmoid sinus (66.4 %) and the sagittal superior sinus (47.6 %). On admission 42.7 % of patients suffered additionally from intracerebral hemorrhage and 12.6 % from congestive infarction. Of the patients 9.5 % (10 out of 105) showed a pathologically reduced activated protein C (APC) resistance and 8.4 % (6 out of 94) a prothrombin mutation. All patients were initially treated with heparin and 88.7 % were switched to cumarin during the course of the disease. The median duration of anticoagulation was 15.75 months (range 1-121 months). On discharge 77.7 % had a good outcome and the in-hospital mortality was 4.7 %. The median time to follow-up in 108 patients was 36 months (range 3-132 months), 74.1 % of patients had a good outcome (MRS 0-2) and 18.5 % died. Independent predictors of in-hospital mortality were MRS on admission (OR 2.2, 95 % CI 1.03-4.7) and of mortality at follow-up the presence of a malignant disease (OR 50.2, 6-423) and intracerebral hemorrhage on admission (OR 10.3, 1.7-62.6). The results of this study are in line with previously published data on CVST. The most prominent clinical risk factors for CVST were female gender and oral contraception. At discharge from hospital and 3 years after CVST approximately 75 % of patients achieved a good clinical outcome. A severe clinical syndrome and the presence of an intracerebral hemorrhage on admission were independent predictors of mortality.
    Der Nervenarzt 01/2014; · 0.80 Impact Factor
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    ABSTRACT: Cerebral venous and sinus thrombosis (CVST) constitutes less than 0.5-1 % of all strokes and occurs predominantly in young female adults. In general the clinical outcome is favorable but 3-15 % of patients die in the acute phase and in the majority of cases due to cerebral herniation. Intensive care treatment analogous to that of severe ischemic infarct leads to an aggressive interdisciplinary therapy concept that can achieve good clinical outcome. Based on five cases of severe CVST treatment options will be presented. All five patients were affected by impending or incipient cerebral herniation and severe focal neurological deficits which resulted in the decision to implement thrombectomy, thrombolysis or hemicraniectomy. Despite the severe course and many intensive care complications which suggested a poor prognosis, all five patients could be transferred to rehabilitation after having survived the acute phase and achieved an amazingly good overall clinical outcome. Considering the life-threatening course of severe CVST, aggressive interdisciplinary management by endovascular thrombectomy and hemicraniectomy can lead to a scarcely expected clinical outcome without disability or severe dependency. This treatment should be performed early and in an escalatory manner in patients with severe CVST who have an increased risk of an unfavorable outcome due to edema, infarction and hemorrhage.
    Der Nervenarzt 01/2014; · 0.80 Impact Factor
  • Europace 01/2014; 16(1):151-2. · 2.77 Impact Factor
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    ABSTRACT: Zerebrale Sinus- und Venenthrombosen (SVT) stellen weniger als 0,5–1 % aller Schlaganfälle dar und kommen gehäuft bei jungen, weiblichen Erwachsenen vor. Generell gilt die Prognose einer SVT als günstig, trotzdem sterben 3–15 % aller Patienten mit SVT in der Akutphase der Erkrankung, meist aufgrund fulminant raumfordernder Stauungsinfarkte oder -blutungen mit nachfolgender zerebraler Herniation. Intensivmedizinische Behandlungsmethoden in Analogie zur Behandlung schwerer ischämischer Infarkte stellen ein aggressives interdisziplinäres Therapiekonzept dar, das anhand von 5 Fällen vorgestellt werden soll.Alle 5 Patienten waren von einer drohenden oder beginnenden zerebralen Herniation und schwerwiegenden fokal-neurologischen Defiziten betroffen, was zur Entscheidung für eine Thrombektomie, Thrombolyse oder Hemikraniektomie (HK) bzw. deren Kombination führte. Trotz der schwer verlaufenden SVTs und trotz vieler intensivmedizinischer Komplikationen, die zunächst eine schlechte Prognose vermuten ließen, konnten alle 5 Patienten nach Überleben der Akutphase in die Rehabilitation verlegt werden und erreichten ein erstaunlich gutes klinisches Ergebnis.In Anbetracht des lebensbedrohlichen Verlaufs von schweren SVTs kann ein aggressives, interdisziplinäres Management inklusive endovaskulärer Thrombektomie und Hemikraniektomie zu einem kaum erwarteten Behandlungsergebnis ohne schwere Behinderung oder starke Abhängigkeit führen. Diese Behandlung sollte vermutlich frühzeitig bei Patienten mit schweren Pansinusthrombosen und hohem Risiko eines ungünstigen Verlaufs durch Entstehung von zerebralen Ödemen, Infarkten oder Blutungen erfolgen.
    Der Nervenarzt 01/2014; 85(2). · 0.80 Impact Factor
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    ABSTRACT: Die zerebrale Sinus-/Venenthrombose (SVT) ist eine seltene Erkrankung, bei der es zu einem thrombotischen Verschluss zerebraler Venen oder Sinus kommt. Wir untersuchten in einer monozentrischen retrospektiven Kohortenstudie klinische Charakteristika, Risikofaktoren, Bildgebungsbefunde und die Prognose unserer Patienten über einen Zeitraum von 15 Jahren.Im Zeitraum von Januar 1998 bis März 2013 wurden alle Patienten, welche in der Neurologischen Klinik der Universität Heidelberg stationär aufgrund einer SVT behandelt wurden, systematisch erfasst. Neben den klinischen Befunden wurde als Skala zur Beurteilung des klinischen Schweregrades die modified Rankin Scale (mRS) verwendet. Zu drei Zeitpunkten erfolgte eine Follow-up-Visite. Bei der Auswertung der Prädiktoren für ein gutes neurologisches Outcome (mRS 0–2) und für die Mortalität bei Entlassung sowie beim Follow-up wurden Odds Ratios zur Verdeutlichung der Stärke der Assoziation berechnet. Signifikante Variablen in der univariaten Analyse wurden in einem logistischen Regressionsmodell auf ihre Unabhängigkeit überprüft.Es konnten 143 Patienten in die Studie eingeschlossen werden. Das mediane Alter lag bei 43 Jahren (17–84, min–max) und 67,4 % der Patienten waren weiblich. Die häufigsten Symptome waren Kopfschmerzen (70,6 %), epileptische Anfälle (50,4 %) und Lähmungen (37,8 %). Der häufigste klinische Risikofaktor war die Einnahme einer oralen Kontrazeption (40,4 %). Die beiden häufigsten Lokalisationen der Thrombose waren der Sinus transversus mit Übergang in den Sinus sigmoideus (66,4 %) und der Sinus sagittalis superior (47,6 %). 42,7 % der Patienten hatten eine begleitende Hirnblutung und 12,6 % einen Stauungsinfarkt. In 9,5 % (10/105) der Fälle konnte eine pathologisch erniedrigte APC (aktiviertes Protein C) -Resistenz nachgewiesen werden und in 8,4 % (6/94) eine Prothrombinmutation. Alle Patienten wurden initial mit Heparinen behandelt und 88,7 % im Verlauf auf Phenprocoumon eingestellt. Die mediane Dauer der Antikoagulation lag bei 15,75 Monaten (1–121). 77,7 % der Patienten hatten bei Entlassung ein gutes Outcome (mRS 0–2) und die Mortalität während des stationären Aufenthaltes lag bei 4,7 %. Die mediane Dauer des Follow-ups von 108 Patienten lag bei 36 Monaten (3–132) und 74,1 % dieser Patienten erreichten ein gutes Outcome (mRS 0–2). 18,5 % der Patienten waren bis dahin verstorben. Unabhängige Prädiktoren für die Mortalität bei Entlassung waren ein hoher mRS bei Aufnahme (OR 2,2, 95 %-CI 1,03–4,7) und für Mortalität beim Follow-up das Vorhandensein eines Malignoms (OR 50,2, 6–423) und eine Hirnblutung bei Aufnahme 10,3 (1,7–62,6).Unsere Ergebnisse orientieren sich eng an der bisher publizierten Datenlage zur SVT. Die wesentlichen klinischen Risikofaktoren für eine SVT waren das weibliche Geschlecht und die Einnahme oraler Kontrazeptiva. Ungefähr 75 % der Patienten hatten bei Entlassung und beim Follow-up nach durchschnittlich 3 Jahren ein gutes Outcome erreicht. Ein schlechter klinischer Zustand bei Aufnahme und das Vorhandensein einer Hirnblutung waren wesentliche Prädiktoren für die Sterblichkeit.
    Der Nervenarzt 01/2014; 85(2). · 0.80 Impact Factor
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    ABSTRACT: To study the time dependent effectiveness of thrombolytic therapy for acute ischaemic stroke in daily clinical practice.DESIGN: A retrospective cohort study using data from a large scale, comprehensive population based state-wide stroke registry in Germany.SETTING: All 148 hospitals involved in acute stroke care in a large state in southwest Germany with 10.4 million inhabitants.PARTICIPANTS: Data from 84 439 patients with acute ischaemic stroke were analysed, 10 263 (12%) were treated with thrombolytic therapy and 74 176 (88%) were not treated.MAIN OUTCOME MEASURES: Primary endpoint was the dichotomised score on a modified Rankin scale at discharge ("favourable outcome" score 0 or 1 or "unfavourable outcome" score 2-6) analysed by binary logistic regression. Patients treated with recombinant tissue plasminogen activator (rtPA) were categorised according to time from onset of stroke to treatment. Analogous analyses were conducted for the association between rtPA treatment of stroke and in-hospital mortality. As a co-primary endpoint the chance of a lower modified Rankin scale score at discharge was analysed by ordinal logistic regression analysis (shift analysis).RESULTS: After adjustment for characteristics of patients, hospitals, and treatment, rtPA was associated with better outcome in a time dependent pattern. The number needed to treat ranged from 4.5 (within first 1.5 hours after onset; odds ratio 2.49) to 18.0 (up to 4.5 hours; odds ratio 1.26), while mortality did not vary up to 4.5 hours. Patients treated with rtPA beyond 4.5 hours (including mismatch based approaches) showed a significantly better outcome only in dichotomised analysis (odds ratio 1.25, 95% confidence interval 1.01 to 1.55) but the mortality risk was higher (1.45, 1.08 to 1.92).CONCLUSION: The effectiveness of thrombolytic therapy in daily clinical practice might be comparable with the effectiveness shown in randomised clinical trials and pooled analysis. Early treatment was associated with favourable outcome in daily clinical practice, which underlines the importance of speeding up the process for thrombolytic therapy in hospital and before admission to achieve shorter time from door to needle and from onset to treatment for thrombolytic therapy.
    BMJ Clinical Research 01/2014; 348:g3429. · 14.09 Impact Factor
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    ABSTRACT: Background In primary and secondary prevention, statins significantly reduce cardiovascular and cerebrovascular events. Pre-interventional statin medication shows a benefit in carotid artery stenosis patients treated with endarterectomy; however, there are few data available for patients treated with stent-angioplasty. The aim of this study was to investigate whether pre-interventional statin therapy is associated with decreased peri-interventional risk of stroke, myocardial infarction, and mortality in patients undergoing stent-angioplasty for internal carotid stenosis. Methods Data for 344 consecutively documented patients with internal carotid artery stenosis treated with stent-angioplasty in the years 2002–2012 at the same stroke center were collected in a prospectively defined database. Risk factors, medication, and indication for therapy were documented. Univariate and multivariate analysis was performed to investigate independent reduction of peri-interventional stroke, myocardial infarction, or death by statin medication prior to stent-angioplasty. Results The median age was 70 years (p25: 63, p75: 76), 75.5% of patients were male, and the median stenosis was 85% according to ECST criteria (p25: 80%, p75: 90%). 20.1% of patients had asymptomatic stenoses, and 60.2% had statin medication before stenting. As per multivariate analysis, pre-interventional statin medication was a predictor for significant peri-interventional risk reduction regarding primary endpoint ischemic stroke, myocardial infarction (MI), or death (odds ratio (OR) 0.31, p = .006). Statins also had a significant protective effect in secondary endpoint ischemic stroke, intracranial bleeding or death (OR 0.39, p = .014), and ischemic stroke or myocardial infarction (OR 0.20; p = .002). Conclusions This study shows that pre-interventional statin medication has a protective effect against peri-interventional stroke, MI, or death in patients with internal carotid artery stenosis treated with stent-angioplasty. Accordingly, statins could be considered as a standard pre-interventional medical therapy in carotid stenting.
    European Journal of Vascular and Endovascular Surgery. 01/2014;

Publication Stats

22k Citations
2,863.47 Total Impact Points


  • 2014
    • University of Toronto
      • Division of Cardiology
      Toronto, Ontario, Canada
  • 1990–2014
    • Universität Heidelberg
      • • Neurological Clinic
      • • Clinik of Neurology
      • • Institute of Clinical Radiology
      • • Abteilung für Neuroradiologie
      Heidelburg, Baden-Württemberg, Germany
  • 2013
    • Massachusetts General Hospital
      • Department of Medicine
      Boston, MA, United States
    • University of Duisburg-Essen
      Essen, North Rhine-Westphalia, Germany
    • University of Leuven
      Louvain, Flanders, Belgium
  • 2012
    • Glasgow Caledonian University
      Glasgow, Scotland, United Kingdom
    • University Hospital Essen
      Essen, North Rhine-Westphalia, Germany
  • 2011–2012
    • Duke University Medical Center
      • Duke Clinical Research Institute
      Durham, NC, United States
    • Charité Universitätsmedizin Berlin
      • Center for Stroke Research Berlin
      Berlin, Land Berlin, Germany
  • 2010–2012
    • Royal Perth Hospital
      Perth City, Western Australia, Australia
    • The University of Western Ontario
      London, Ontario, Canada
    • Universität des Saarlandes
      • Klinik für Innere Medizin III - Kardiologie, Angiologie und internistische Intensivmedizin
      Saarbrücken, Saarland, Germany
  • 2004–2010
    • University College London
      • • Department of Brain Repair and Rehabilitation
      • • Institute of Neurology
      London, ENG, United Kingdom
    • Klinikum Ludwigshafen
      Ludwigshafen, Rheinland-Pfalz, Germany
  • 2009
    • University of St Andrews
      • School of Psychology and Neuroscience
      Saint Andrews, SCT, United Kingdom
    • Boehringer Ingelheim
      Ingelheim, Rheinland-Pfalz, Germany
  • 2007–2009
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
    • Universidad Autónoma de Madrid
      Madrid, Madrid, Spain
    • Tufts University
      • Institute for Clinical Research and Health Policy Studies
      Boston, GA, United States
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2006–2009
    • Universitätsklinikum Erlangen
      • Department of Neurology
      Erlangen, Bavaria, Germany
  • 2003–2009
    • University of Glasgow
      • Institute of Cardiovascular and Medical Sciences
      Glasgow, Scotland, United Kingdom
    • Christian-Albrechts-Universität zu Kiel
      • Unit of Neurobiology
      Kiel, Schleswig-Holstein, Germany
  • 2008
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
    • University of California, San Francisco
      San Francisco, California, United States
    • University of Texas Health Science Center at San Antonio
      • Department of Neurology
      San Antonio, TX, United States
    • Karolinska Institutet
      • Institutionen för klinisk neurovetenskap
      Solna, Stockholm, Sweden
  • 2004–2008
    • University of Iowa
      • Department of Neurology
      Iowa City, IA, United States
  • 2006–2007
    • Cleveland Clinic
      Cleveland, Ohio, United States
  • 2002
    • Universität Mannheim
      Mannheim, Baden-Württemberg, Germany
    • Università degli Studi di Perugia
      Perugia, Umbria, Italy
    • University of Hamburg
      • Department of Neurology
      Hamburg, Hamburg, Germany
    • University of Cincinnati
      • Department of Neurology
      Cincinnati, OH, United States
  • 1997–2001
    • Technische Universität Dresden
      • Abteilung Neuroradiologie
      Dresden, Saxony, Germany
    • Sapienza University of Rome
      Roma, Latium, Italy
  • 2000
    • German Cancer Research Center
      Heidelburg, Baden-Württemberg, Germany
    • Helsinki University Central Hospital
      • Department of Neurology
      Helsinki, Province of Southern Finland, Finland
  • 1999
    • University of Leipzig
      • Klinik und Poliklinik für Neurologie
      Leipzig, Saxony, Germany
  • 1998
    • Carl Gustav Carus-Institut
      Pforzheim, Baden-Württemberg, Germany
  • 1996
    • Inselspital, Universitätsspital Bern
      • Department of Neurology
      Berna, Bern, Switzerland
  • 1991–1992
    • The Scripps Research Institute
      • Department of Molecular and Experimental Medicine
      La Jolla, CA, United States
  • 1982–1989
    • RWTH Aachen University
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
  • 1986–1988
    • University Hospital RWTH Aachen
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany