Showing papers by "Werner Hacke published in 2011"
TL;DR: In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism and there was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivroxaban group.
Abstract: Methods In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism. Results In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P = 0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P = 0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P = 0.02) and fatal bleeding (0.2% vs. 0.5%, P = 0.003) in the rivaroxaban group. Conclusions In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.)
7,716 citations
TL;DR: The results of this trial are expected to directly influence decision making in patients 61-years and older with malignant middle cerebral artery infarcts, because these patients have generally been treated later and less aggressively.
Abstract: Background Patients with severe space-occupying – so-called malignant – middle cerebral artery infarcts have a poor prognosis even under maximum intensive care treatment. Randomised trials demonstrated that early hemicraniectomy reduces mortality from about 70% to 20% without increasing the risk of being very severely disabled. Hemicraniectomy increases the chance to survive completely independent more than fivefold and doubles the chance to survive at least partly independent. Only patients up to 60-years have been included in these trials. However, patients older than 60-years represent about 50% of all patients with malignant middle cerebral artery infarcts. Data from observational studies, suggesting that older patients may not profit from hemicraniectomy, are inconclusive, because these patients have generally been treated later and less aggressively. This leads to great uncertainty in everyday clinical practice.
Aims To investigate the efficacy of early hemicraniectomy in patients older than 60-years with malignant MCA infarcts.
Materials & Methods DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY II is a randomised controlled trial including patients 61-years and older with malignant middle cerebral artery infarcts. Patients are randomised to either maximum conservative treatment alone or in addition to early hemicraniectomy within 48 h after symptom onset. The trial uses a sequential design with a maximum number of 160 patients to be enrolled (ISRCTN 21702227).
Discussion In the face of an ageing population, the potential benefit of hemicraniectomy in older patients is of major clinical relevance, but remains controversial.
Conclusion The results of this trial are expected to directly influence decision making in these patients.
125 citations
TL;DR: Poor outcome and mortality after ischemic stroke are strongly associated with low and further decreasing Hb and Hct levels, which might be more relevant and accessible to treatment than are baseline levels.
Abstract: Background and Purpose— Although conceivably relevant for penumbra oxygenation, the optimal levels of hemoglobin (Hb) and hematocrit (Hct) in patients with acute ischemic stroke are unknown.
Methods— We identified patients from our prospective local stroke database who received intravenous thrombolysis based on multimodal magnet resonance imaging during the years 1998 to 2009. A favorable outcome at 3 months was defined as a modified Rankin Scale score ≤2 and a poor outcome as a modified Rankin Scale score ≥3. The dynamics of Hemoglobin (Hb), Hematocrit (Hct), and other relevant laboratory parameters as well as cardiovascular risk factors were retrospectively assessed and analyzed between these 2 groups.
Results— Of 217 patients, 114 had a favorable and 103 a poor outcome. In a multivariable regression model, anemia until day 5 after admission (odds ratio [OR]=2.61; 95% CI, 1.33 to 5.11; P =0.005), Hb nadir (OR=0.81; 95% CI, 0.67 to 0.99; P =0.038), and Hct nadir (OR=0.93; 95% CI, 0.87 to 0.99; P =0.038) remained independent predictors for poor outcome at 3 months. Mortality after 3 months was independently associated with Hb nadir (OR=0.80; 95% CI, 0.65 to 0.98; P =0.028) and Hb decrease (OR=1.34; 95% CI, 1.01 to 1.76; P =0.04) as well as Hct decrease (OR=1.12; 95% CI, 1.01 to 1.23; P =0.027).
Conclusions— Poor outcome and mortality after ischemic stroke are strongly associated with low and further decreasing Hb and Hct levels. This decrease of Hb and Hct levels after admission might be more relevant and accessible to treatment than are baseline levels.
71 citations
TL;DR: The data are consistent with, but do not prove the hypothesis that early addition of clopidogrel to acetylsalicylic acid in patients with transient ischaemic attack and ischaemia stroke of arterial origin may be more effective and acceptably safe compared with acetyl salicylic Acid alone.
Abstract: BackgroundThe Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilisation, Management and Avoidance (CHARISMA) trial reported no statistically significant benefit of adding clopidogrel t...
69 citations
TL;DR: PxAF occurs more often than pAF in stroke/TIA patients, and it is important to develop and evaluate sensitive methods for detecting pxAF.
Abstract: Background: Atrial fibrillation (AF) is a common cause of ischemic stroke and transient ischemic attack (TIA). More extensive diagnostic effort is required to detect paroxysmal AF (
64 citations
TL;DR: In stable patients, moderate or severe bleeding is associated with a significantly increased risk of all-cause, cardiovascular, and cancer mortality, however, this risk appeared different in subjects on single antiplatelet therapy versus DAPT.
42 citations
TL;DR: Investigation of frequency of pre- and post-treatment elevated BP and its relation to intracerebral hemorrhage and symptomatic ICH found neither the frequency of BP protocol violations nor the BP levels predicted ICH or sICH in univariate or multivariate analyses.
Abstract: Background and Purpose— Significantly increased blood pressure (BP) is common in patients receiving intravenous thrombolysis (IVT). We aimed to investigate frequency of pre- and post-treatment elevated BP and its relation to intracerebral hemorrhage (ICH) and symptomatic ICH (sICH), respectively.
Methods— Data for patients treated with intravenous thrombolysis in the years 2007 to 2009 were retrospectively extracted from our prospectively conducted local stroke database. All documented BP levels from admission to follow-up imaging scan were analyzed. BP protocol violations were defined as systolic BP >185mm Hg and/or diastolic BP >110 mm Hg. sICH was defined as ICH plus worsening of the National Institute of Health Stroke Scale ≥4 points.
Results— BP protocol violation before IVT emerged in 12.6% and during the course of IVT in 40.1% of 427 patients. sICH occurred in 10 (2.3%) and ICH in general occurred in 51 (11.9%) of 427 patients. Proportions of BP protocol violations were similar in patients without ICH, with any ICH, and with sICH (3.1% versus 2.8% versus 3.2%). Systolic BP levels and mean arterial pressure did not differ between patients without ICH, patients with any ICH, and patients with sICH. In the multivariate analysis, only early CT findings independently predicted ICH (OR, 2.39; 95% CI, 1.25–4.61; P =0.009).
Conclusions— BP protocol violations are common before and during the course of IVT, but neither the frequency of BP protocol violations nor the BP levels predicted ICH or sICH in univariate or multivariate analyses.
23 citations
TL;DR: To answer the questions regarding the efficacy of hemicraniectomy in older patients with malignant middle cerebral artery infarctions, several facts and open questions must be considered.
Abstract: ### The Case:
A 70 year-old right-handed woman with a massive right MCA infarction and 3 mm midline shift is seen within 17 hours of onset.
### The Questions:
### The Controversy:
Early decompressive hemicraniectomy in older patients with non-dominant hemispheric infarction improves outcome.
To answer the questions regarding the efficacy of hemicraniectomy in older patients with malignant middle cerebral artery infarctions, several facts and open questions must be considered. First, the natural course of complete middle cerebral artery infarctions is associated with early death in 70% to 80% of cases. This “malignant” and deadly course can also be seen in older patients. Second, in case of survival, recovery with a complete functional independent outcome is almost impossible.1 Third, there is no proven standard medical or conservative critical care management. Standard care is largely ineffective and probably not better than palliative care.1,2 Osmotherapy, hyperventilation, buffers, barbiturates, and hypothermia are unproven, ineffective, or even detrimental.2 Fourth, the efficacy …
19 citations
TL;DR: It is found that it is possible to change healthcare provider behaviour and achieve an approximate 10% improvement in the process of care indicators, which are clinically significant in the context of stroke care delivery.
Abstract: Despite the high incidence of stroke, the prevalence of millions of stroke survivors world-wide, and the growing body of evidence-based research on stroke management, wide variations in the quality of stroke care delivery persist. Audits of stroke care delivery in multiple jurisdictions have demonstrated variations and gaps in the quality of stroke care, with the result that some stroke patients do not receive medical care consistent with evidence-based standards (1–4). Explanations for deficiencies in care are multifactorial, but may include: variations in knowledge about stroke (public and provider awareness and recognition of stroke signs and symptoms) regional or institutional resources (such as availability of computed tomography, medical and rehabilitation specialists in stroke care and telemedicine technologies) organisational levels of stroke care (use of acute stroke units or stroke protocols and agreements with emergency medical services, participation in a stroke registry), and variations in the opinions and knowledge of local health care providers of evidence-based stroke care delivery (5). Clinical practice guidelines have become a common element of clinical care throughout the world. Such guidelines have the potential to improve the care received by patients by promoting interventions of proven benefit and discouraging ineffective ones (6). Grimshaw examined the impact of guideline dissemination and implementation strategies through a systematic review of 235 studies. He found that it is possible to change healthcare provider behaviour and achieve an approximate 10% improvement in the process of care indicators (7). These findings are clinically significant in the context of stroke care delivery, where improvements in processes of care have been linked to improved patient outcomes (8). The combined development of evidence-based clinical guidelines, which describe ‘what’ should be done, and validated performance measures, which describe ‘how well’ it is being done, are powerful tools to drive an international agenda to improve and monitor the quality of stroke care across the continuum. Given the significant burden of stroke world-wide, the need to develop standardised best practice guidelines for stroke, based on the best available evidence and adaptable to local/regional contexts, has become imperative for all stroke clinicians. In 2007, the World Stroke Organization created a Stroke Guidelines Subcommittee to exemplify its commitment to stroke best practices uptake and implementation. The mandate of this subcommittee is to establish a framework and action plan for collaboration in the development and dissemination of stroke guidelines across the continuum of care and across organisations and jurisdictions. The goals of the Guidelines Subcommittee are to: create a mechanism for conducting and/or sharing systematic literature reviews to reduce wasteful duplication across organisations identify priority areas for new guideline development based on strong emerging research findings develop a common approach to the dissemination of stroke guidelines to maximise uptake collaborate on education initiatives related to stroke guideline uptake and implementation in stroke care delivery, and collaborate in the evaluation of the impact of stroke guidelines on patient outcomes with the goal of developing international targets and benchmarks for inclusion in stroke guideline documentation.
8 citations
TL;DR: In this paper, Thrombin and Faktor Xa ansetzender oraler Inhibitoren ermoglicht eine zuverlassige antikoagulation ohne regelmasiges Gerinnungsmonitoring in grosen randomisierten Primar-and Sekundarprophylaxestudien schutzte the orale AntikoAGulation (OAK) with Vitamin-K-Antagonisten (VKA) wesentlich wirksamer als Thrombozytenaggregations
Abstract: Vorhofflimmern (VHF) verursacht mindestens 20% aller ischamischen Schlaganfalle In grosen randomisierten Primar- und Sekundarprophylaxestudien schutzte die orale Antikoagulation (OAK) mit Vitamin-K-Antagonisten (VKA) wesentlich wirksamer als Thrombozytenaggregationshemmer vor Schlaganfallen Aufgrund der problematischen pharmakologischen Eigenschaften der VKA werden aber zu wenige VHF-Patienten mit OAK behandelt Die gezielte Entwicklung spezifisch an den zentralen Gerinnungsfaktoren Thrombin und Faktor Xa ansetzender oraler Inhibitoren ermoglicht eine zuverlassige Antikoagulation ohne regelmasiges Gerinnungsmonitoring In der vorliegenden Ubersicht werden zunachst die pharmakologischen Eigenschaften der verschiedenen Thrombin- und Faktor-Xa-Inhibitoren verglichen Von den vier grosen randomisierten Phase-III-Studien bei VHF (RELY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) mit dem primaren Wirksamkeitsendpunkt Schlaganfall weisen die bereits publizierten Daten der RELY-Studie auf eine uberlegene Wirksamkeit von Dabigatranetexilat (2-mal 150 mg/Tag) bei signifikant niedrigerem Hirnblutungsrisiko gegenuber Warfarin hin Ahnlich gunstige Ergebnisse ergeben sich aus vorlaufigen Daten zu Rivaroxaban Apixaban war in der AVERROES-Studie wirksamer als Acetylsalicylsaure bei vergleichbarem Blutungsrisiko Damit deutet sich ein insgesamt gunstiges Nutzen-Risiko-Verhaltnis fur die neuen Substanzen bei groserem Patientenkomfort an Noch ungeloste Fragen betreffen die Prufung der Patientenadharenz durch geeignete Gerinnungstests sowie die Notfallgerinnungsdiagnostik und -therapie bei ischamischen und hamorrhagischen Schlaganfallen unter neuen OAK
6 citations
Journal Article•
TL;DR: This work investigated the prevalence of prior myocardial infarction and incidence of future ischemic cardiova in patients with atrial fibrillation and found that pre-existing coronary artery disease is more common than previously thought.
Abstract: Background: Coronary artery disease is common in patients with atrial fibrillation (AF). We investigated the prevalence of prior myocardial infarction (MI) and incidence of future ischemic cardiova...
TL;DR: In this article, the authors show that 10% to 15% of all patients with intrazerebrale Blutung (ICB) verursacht will receive a palliative treatment.
Abstract: Etwa 10–15% aller Schlaganfalle werden durch eine nichtaneurysmatische intrazerebrale Blutung (ICB) verursacht. Aufgrund der Altersstruktur der Bevolkerung ist von einer steigenden Inzidenz auszugehen. Die Mortalitat wird in Arbeiten aus den 1990er Jahren auf bis zu 50% geschatzt. Es ist jedoch zu vermuten, dass die schlechte Prognose durch eine „sich selbst erfullende Prophezeiung“ mitbedingt ist, im Rahmen derer Patienten mit ICB haufig nur eine palliative Therapie erhalten. Eine neuere Studie zeigte, dass alleine die Behandlung auf einer spezialisierten neurologischen Intensivstation mit einer Reduktion der Mortalitat assoziiert war. In den letzten Jahren wurden erhebliche Anstrengungen unternommen, Therapiekonzepte fur die intrazerebrale Blutung zu entwickeln und in randomisierten Studien zu prufen. Neben dem neurologischen Status bei Aufnahme ist das Blutungsvolumen ein entscheidender prognostischer Faktor, und die rasche Eingrenzung der Blutung wurde als wichtiger therapeutischer Ansatz identifiziert. Im Anschluss an eine vielversprechende Dosisfindungsstudie zeigte eine Phase-III-Studie zwar eine Verringerung der Hamatomzunahme nach Gabe von aktiviertem Faktor VIIa innerhalb der ersten 4 h, ein signifikanter Effekt auf das klinische Outcome konnte jedoch nicht nachgewiesen werden. Ahnliche Ergebnisse fanden sich in einer randomisierten Studie zur Blutdrucksenkung in der Akutphase. Der Beleg aus randomisierten Studien, dass eine Verminderung des Hamatomwachstums sich in einer relevanten Verbesserung des Outcomes niederschlagt, steht somit weiterhin aus. Auch der Wert der chirurgischen Therapie ist nicht abschliesend geklart. In der bisher grosten randomisierten Studie schien nur eine kleine Subgruppe der Patienten mit oberflachlich gelegener Blutung von der Ausraumung des Hamatoms zu profitieren. Diese Subgruppe wird derzeit in einer Nachfolgestudie untersucht. Ob die verbesserte intensivmedizinische Versorgung auch das funktionelle Outcome nachhaltig positiv beeinflusst, werden Daten der kommenden Jahre zeigen.
TL;DR: In this article, a number of such Grenzsituationen aufgedeckt and diskutiert are discussed, e.g., the Thrombolyse auserhalb geltender Zulassungskriterien (z.b. B. Vorhofflimmern and frischer Stent), or haufig diskuterten Risikokonstellationen (Demenz, Anamnese fur Sturze, Zustand nach intrazerebraler Blutung).
Abstract: Bei der Behandlung von Schlaganfallpatienten ist fur eine Vielzahl der therapeutischen Entscheidungen im Alltag die medizinische Evidenz begrenzt oder nicht vorhanden. Dies betrifft Behandlungssituationen sowohl in der Akuttherapie als auch in der Sekundarpravention. In diesem Beitrag werden solche Grenzsituationen aufgedeckt und diskutiert. Beispiele sind die Thrombolyse auserhalb geltender Zulassungskriterien (z. B. hohes Alter, orale Antikoagulation) und die Sekundarpravention bei Patienten mit konkurrierenden Behandlungsindikationen (z. B. Vorhofflimmern und frischer Stent) oder haufig diskutierten Risikokonstellationen (Demenz, Anamnese fur Sturze, Zustand nach intrazerebraler Blutung). Neben der Diskussion der aktuellen Datenlage werden eigene Erfahrungen berichtet und konkrete Empfehlungen zum Vorgehen gegeben.
21 Sep 2011
TL;DR: Proximal occlusions of the middle cerebral artery can be treated successfully within the first 6 h from stroke onset by catheter-based intra-arterial administration of plasminogen activator leading to a significant improvement of outcome.
Abstract: Der ischamische Schlaganfall ist ein medizinischer Notfall, der gemas dem „Time-is-brain“-Konzept schnellstmoglich behandelt werden muss. Die derzeit einzig nachgewiesen wirksame Akutbehandlung stellt die i.v.-Gabe von „recombinant tissue plasminogen activator“ (rt-PA) dar, die innerhalb eines 4,5-h-Fensters wirksam und sicher, allerdings bislang nur innerhalb der ersten 3 h nach Symptombeginn zugelassen ist (0,9 mg/kgKG, Maximum von 90 mg, 10% der Gesamtdosis als Bolus, die restlichen 90% im Anschluss als Infusion uber 60 min). Den therapeutischen Effekt Magnetresonanztomographie(MRT)-basierter thrombolytischer Therapien jenseits des 4,5-h-Fensters gilt es noch zu untersuchen. Bei proximalen Verschlussen der A. cerebri media fuhrt die katheterbasierte intraarterielle Behandlung mit einem Plasminogenaktivator innerhalb eines 6-h-Zeitfensters zu einer signifikanten Verbesserung des Outcomes und kann als individueller Heilversuch angesehen werden. Akute Basilarisverschlusse sollten in spezialisierten Zentren mit intraarterieller Applikation von Urokinase, rt-PA oder mechanischer Rekanalisation behandelt werden; hierbei ist die i.v.-Thrombolyse auch jenseits des 3-h-Zeitfensters eine akzeptable Alternative.