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ZusammenfassungDie Durchführung einer oralen Antikoagulation ist bei Patienten mit einer zerebralen Amyloidangiopathie eine therapeutische Herausforderung. Die Assoziation der zerebralen Amyloidangiopathie mit Lobärblutungen, eine hohe Mortalität intrazerebraler Blutungen insbesondere unter oraler Antikoagulation sowie das hohe Rezidivrisiko solcher Blutungen erfordern eine strenge und interdisziplinäre Risiko-Nutzen-Abwägung. Vitamin-K-Antagonisten erhöhen das Risiko für die mit intrazerebralen Blutungen vergesellschaftete Mortalität um 60 % und sollten daher möglichst vermieden bzw. speziellen klinischen Situationen (z. B. mechanischer Aortenklappenersatz) vorbehalten sein. Auch der Einsatz von neuen oralen Antikoagulanzien und Thrombozytenaggregationshemmern bedarf einer strengen Risiko-Nutzen-Abwägung, da auch diese Substanzen das zerebrale Blutungsrisiko erhöhen. Insbesondere bei Patienten mit einer absoluten Arrhyhtmie bei Vorhofflimmern ist der interventionelle Vorhofohrverschluss eine therapeutische Alternative. Darüber hinaus sind weitere klinische Implikationen bei Patienten mit zerebraler Amyloidangiopathie Gegenstand dieser Literaturübersicht, beispielsweise Besonderheiten nach akutem ischämischem Schlaganfall und erforderlicher Sekundärprophylaxe, bei vorherigen intrazerebralen Blutungen und bei Patienten mit kognitiven Defiziten.

Aims We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke. Methods The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke. Results At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05–7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04–10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24–9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01–0.47, P n = 56], CHA2DS2-VASc score [OR per point 1.47, 95% CI 1.08–2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28–2.84, P Conclusion At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge. Clinical trial registration NCT02306824.

Aims The Berlin Atrial Fibrillation Registry was designed to analyse oral anticoagulation (OAC) prescription in patients with atrial fibrillation (AF) and acute ischaemic stroke. Methods and results This investigator-initiated prospective multicentre registry enrolled patients at all 16 stroke units located in Berlin, Germany. The ongoing telephone follow-up is conducted centrally and will cover 5 years per patient. Within 2014 and 2016, 1080 patients gave written informed consent and 1048 patients were available for analysis. Median age was 77 years [interquartile range (IQR) 72–83], 503 (48%) patients were female, and 254 (24%) had a transient ischaemic attack (TIA). Overall, 470 (62%) out of 757 patients with known AF and a (pre-stroke) CHA2DS2-VASc ≥ 1 were anticoagulated at the time of stroke. At hospital discharge, 847 (81.3%) of 1042 patients were anticoagulated. Thereof 710 (68.1%) received a non-vitamin K-dependent oral anticoagulant (NOAC) and 137 (13.1%) a vitamin K antagonist (VKA). Pre-stroke intake of a NOAC [odds ratio (OR) 15.6 (95% confidence interval, 95% CI 1.97–122)] or VKA [OR 0.04 (95% CI 0.02–0.09)], an index TIA [OR 0.56 (95% CI 0.34–0.94)] rather than stroke, heart failure [OR 0.49 (95% CI 0.26–0.93)], and endovascular thrombectomy at hospital admission [OR 12.9 (95% CI 1.59–104)] were associated with NOAC prescription at discharge. Patients’ age or AF type had no impact on OAC or NOAC use, respectively. Conclusion About 60% of all registry patients with known AF received OAC at the time of stroke or TIA. At hospital discharge, more than 80% of AF patients were anticoagulated and about 80% of those were prescribed a NOAC.

Aims Several studies showed reduced stroke severity in patients with atrial fibrillation (AF) if the international normalized ratio (INR) was ≥ 2 at stroke onset. There are no respective data for non-vitamin K-dependent oral anticoagulants (NOACs). The aim of this study was to compare the impact of NOAC or phenprocoumon intake on stroke severity. Methods and results In this single-centre observational study, 3669 patients with acute ischaemic stroke were retrospectively analysed regarding AF status and medication immediately before admission. Using multivariable regression, we analysed the association of pre-admission anticoagulation with severe stroke (National Institutes of Health Stroke Scale score ≥ 11) on admission and poor outcome at discharge (modified Rankin scale score > 2). Before the index stroke, 655 patients had known AF and a CHA2DS2-VASc score ≥ 2. While 325 (49.6%) patients were anticoagulated, 159 (24.3%) were prescribed a NOAC and 75 (11.5%) phenprocoumon patients had an INR ≥ 2 on admission. Compared with AF patients without medical stroke prevention, an INR ≥ 2 [OR 0.23 (95% CI 0.10–0.53)] or NOAC intake [OR 0.48 (95% CI 0.27–0.86)] were associated with a lower probability of severe stroke after adjustment for confounders, while an INR

The incidence of stroke and dementia are diverging across the world, rising for those in low- and middle-income countries and falling in those in high-income countries. This suggests that whatever factors cause these trends are potentially modifiable. At the population level, neurological disorders as a group account for the largest proportion of disability-adjusted life years globally (10%). Among neurological disorders, stroke (42%) and dementia (10%) dominate. Stroke and dementia confer risks for each other and share some of the same, largely modifiable, risk and protective factors. In principle, 90% of strokes and 35% of dementias have been estimated to be preventable. Because a stroke doubles the chance of developing dementia and stroke is more common than dementia, more than a third of dementias could be prevented by preventing stroke. Developments at the pathological, pathophysiological, and clinical level also point to new directions. Growing understanding of brain pathophysiology has unveiled the reciprocal interaction of cerebrovascular disease and neurodegeneration identifying new therapeutic targets to include protection of the endothelium, the blood-brain barrier, and other components of the neurovascular unit. In addition, targeting amyloid angiopathy aspects of inflammation and genetic manipulation hold new testable promise. In the meantime, accumulating evidence suggests that whole populations experiencing improved education, and lower vascular risk factor profiles (e.g., reduced prevalence of smoking) and vascular disease, including stroke, have better cognitive function and lower dementia rates. At the individual levels, trials have demonstrated that anticoagulation of atrial fibrillation can reduce the risk of dementia by 48% and that systolic blood pressure lower than 140 mmHg may be better for the brain. Based on these considerations, the World Stroke Organization has issued a proclamation, endorsed by all the major international organizations focused on global brain and cardiovascular health, calling for the joint prevention of stroke and dementia. This article summarizes the evidence for translation into action.

Aims Therapeutic oral anticoagulation on hospital admission reduces morbidity and mortality after acute ischaemic stroke in patients with atrial fibrillation (AF). The underlying mechanism is not fully understood. In order to assess the impact of INR-level on admission on stroke volume, lesion pattern and the frequency of intracranial arterial occlusion, we analysed serial MRI measurements in AF patients suffering acute ischaemic stroke. Methods and results This subgroup analysis of the prospective '1000Plus' study included patients with acute ischaemic stroke and known AF or a first episode of AF in hospital. All patients underwent serial brain magnetic resonance imaging. Stroke patients were categorized as follows: Group1, phenprocoumon intake, international normalized ratio (INR) ≥1.7 on admission, no thrombolysis; Group2, INR

RESULTS Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels