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1.
Clin Res Cardiol ; 110(7): 938-958, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34143285

RESUMO

This expert opinion paper on cardiac imaging after acute ischemic stroke or transient ischemic attack (TIA) includes a statement of the "Heart and Brain" consortium of the German Cardiac Society and the German Stroke Society. The Stroke Unit-Commission of the German Stroke Society and the German Atrial Fibrillation NETwork (AFNET) endorsed this paper. Cardiac imaging is a key component of etiological work-up after stroke. Enhanced echocardiographic tools, constantly improving cardiac computer tomography (CT) as well as cardiac magnetic resonance imaging (MRI) offer comprehensive non- or less-invasive cardiac evaluation at the expense of increased costs and/or radiation exposure. Certain imaging findings usually lead to a change in medical secondary stroke prevention or may influence medical treatment. However, there is no proof from a randomized controlled trial (RCT) that the choice of the imaging method influences the prognosis of stroke patients. Summarizing present knowledge, the German Heart and Brain consortium proposes an interdisciplinary, staged standard diagnostic scheme for the detection of risk factors of cardio-embolic stroke. This expert opinion paper aims to give practical advice to physicians who are involved in stroke care. In line with the nature of an expert opinion paper, labeling of classes of recommendations is not provided, since many statements are based on expert opinion, reported case series, and clinical experience.

2.
Front Neurol ; 12: 665614, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163423

RESUMO

Background and Purpose: Clinical outcome and mortality after endovascular thrombectomy (EVT) in patients with ischemic stroke are commonly assessed after 3 months. In patients with acute kidney injury (AKI), unfavorable results for 3-month mortality have been reported. However, data on the in-hospital mortality after EVT in this population are sparse. In the present study, we assessed whether AKI impacts in-hospital and 3-month mortality in patients undergoing EVT. Materials and Methods: From a prospectively recruiting database, consecutive acute ischemic stroke patients receiving EVT between 2010 and 2018 due to acute large vessel occlusion were included. Post-contrast AKI (PC-AKI) was defined as an increase of baseline creatinine of ≥0.5 mg/dL or >25% within 48 h after the first measurement at admission. Adjusting for potential confounders, associations between PC-AKI and mortality after stroke were tested in univariate and multivariate logistic regression models. Results: One thousand one hundred sixty-nine patients were included; 166 of them (14.2%) died during the acute hospital stay. Criteria for PC-AKI were met by 29 patients (2.5%). Presence of PC-AKI was associated with a significantly higher risk of in-hospital mortality in multivariate analysis [odds ratio (OR) = 2.87, 95% confidence interval (CI) = 1.16-7.13, p = 0.023]. Furthermore, factors associated with in-hospital mortality encompassed higher age (OR = 1.03, 95% CI = 1.01-1.04, p = 0.002), stroke severity (OR = 1.05, 95% CI = 1.03-1.08, p < 0.001), symptomatic intracerebral hemorrhage (OR = 3.20, 95% CI = 1.69-6.04, p < 0.001), posterior circulation stroke (OR = 2.85, 95% CI = 1.72-4.71, p < 0.001), and failed recanalization (OR = 2.00, 95% CI = 1.35-3.00, p = 0.001). Conclusion: PC-AKI is rare after EVT but represents an important risk factor for in-hospital mortality and for mortality within 3 months after hospital discharge. Preventing PC-AKI after EVT may represent an important and potentially lifesaving effort in future daily clinical practice.

3.
Eur Neurol ; 84(5): 354-360, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34167122

RESUMO

INTRODUCTION: Chronic kidney disease is common in patients with acute ischemic stroke. We investigated whether chronic kidney disease has an impact on anticoagulation treatment recommendations after ischemic stroke or transient ischemic attack (TIA) related with atrial fibrillation (AF). MATERIALS AND METHODS: We extracted treatment-related data concerning stroke/TIA patients with AF and available estimated glomerular filtration rates (eGFR) from a monocentric prospective German stroke registry. Chronic kidney disease was defined as eGFR <60 mL/min/1.73 m2. Using uni- and multivariate logistic regression analyses, we investigated whether chronic kidney disease was associated with a lower probability to be treated with anticoagulation early after stroke. RESULTS: A total of 273 patients entered the analysis. In 242 AF patients (88.6%), oral anticoagulation was recommended after stroke. In multivariate logistic regression analysis, chronic kidney disease was not identified as an independent factor for the decision against anticoagulation (OR 1.63, 95% CI: 0.50-5.31, p = 0.421); only increasing age (OR 1.10, 95% CI: 1.00-1.21, p = 0.061) and a modified Rankin Scale >3 at discharge (OR 3.41, 95% CI: 0.88-13.24, p = 0.077) showed a nonsignificant trend for the decision to omit anticoagulation. A total of 155 of 167 patients (92.8%) were still anticoagulated at follow-up. A total of 44 patients with chronic kidney disease completed follow-up, and of those, 37 were still anticoagulated (84%). In patients without chronic kidney disease, 118/167 (70.7%) had continued anticoagulation (p = 0.310). CONCLUSION: Our results show that chronic kidney disease was not the main factor in the decision to withhold oral anticoagulation in patients with recent stroke/TIA and AF.

4.
Case Rep Neurol Med ; 2021: 5517934, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055433

RESUMO

Thunderclap headache is frequently associated with serious intracranial vascular disorders and a usual reason for emergency department admissions. Association of thunderclap headaches with autoimmune disorders, such as steroid-responsive encephalopathy with autoimmune thyroiditis (SREAT), is highly unusual. Here, we report a patient who presented with high-intensity headache of abrupt onset. Cerebrospinal fluid (CSF) analysis revealed moderate lymphocytic pleocytosis without evidence of infectious, neoplastic, or metabolic causes. Brain magnetic resonance imaging showed no specific pathologies, and examinations for neuronal antibodies in serum and CSF were negative. The medical history revealed that seven years before, an episode of an aseptic meningoencephalitis with remarkable response to steroids was present. Finally, increased levels of serum anti-TPO antibodies were identified, and against the background of a previous steroid-responsive aseptic meningoencephalitis, diagnosis of SREAT was highly probable. Methylprednisolone therapy was initiated, and the patient recovered completely. In particular, because most SREAT patients respond very well to steroids, this case underlines the importance of taking SREAT into consideration during the assessment of a high-intensity headache of abrupt onset.

5.
Lancet Neurol ; 20(6): 426-436, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34022169

RESUMO

BACKGROUND: Systematic electrocardiogram (ECG) monitoring improves detection of covert atrial fibrillation in stroke survivors but the effect on secondary prevention is unknown. We aimed to assess the effect of systematic ECG monitoring of patients in hospital on the rate of oral anticoagulant use after 12 months. METHODS: In this investigator-initiated, randomised, open-label, parallel-group multicentre study with masked endpoint adjudication, we recruited patients aged at least 18 years with acute ischaemic stroke or transient ischaemic attack without known atrial fibrillation in 38 certified stroke units in Germany. Patients were randomly assigned (1:1) to usual diagnostic procedures for atrial fibrillation detection (control group) or additional Holter-ECG recording for up to 7 days in hospital (intervention group). Patients were stratified by centre using a random permuted block design. The primary outcome was the proportion of patients on oral anticoagulants at 12 months after the index event in the intention-to-treat population. Secondary outcomes included the number of patients with newly diagnosed atrial fibrillation in hospital and the composite of recurrent stroke, major bleeding, myocardial infarction, or death after 6 months, 12 months, and 24 months. This trial was registered with ClinicalTrials.gov, NCT02204267, and is completed and closed for participants. FINDINGS: Between Dec 9, 2014, and Sept 11, 2017, 3465 patients were randomly assigned, 1735 (50·1%) to the intervention group and 1730 (49·9%) to the control group. Oral anticoagulation status was available in 2920 (84·3%) patients at 12 months (1484 [50·8%] in the intervention group and 1436 [49·2%] in the control group). For the primary outcome, at 12 months, 203 (13·7%) of 1484 patients in the intervention group versus 169 (11·8%) of 1436 in the control group were on oral anticoagulants (odds ratio [OR] 1·2 [95% CI 0·9-1·5]; p=0·13). Atrial fibrillation was newly detected in patients in hospital in 97 (5·8%) of 1714 in the intervention group versus 68 (4·0%) of 1717 in the control group (hazard ratio [HR] 1·4 [95% CI 1·0-2·0]; p=0·024). The composite of cardiovascular outcomes and death did not differ between patients randomly assigned to the intervention group versus the control group at 24 months (232 [13·5%] of 1714 vs 249 [14·5%] of 1717; HR 0·9 [0·8-1·1]; p=0·43). Skin reactions due to study ECG electrodes were reported in 56 (3·3%) patients in the intervention group. All-cause death occured in 73 (4·3%) patients in the intervention group and in 103 (6·0%) patients in the control group (OR 0·7 [0·5-0·9]). INTERPRETATION: Systematic core centrally reviewed ECG monitoring is feasible and increases the detection rate of atrial fibrillation in unselected patients hospitalised with acute ischaemic stroke or transient ischaemic attack, if added to usual diagnostic care in certified German stroke units. However, we found no effect of systematic ECG monitoring on the rate of oral anticoagulant use after 12 months and further efforts are needed to improve secondary stroke prevention. FUNDING: Bayer Vital. TRANSLATION: For the German translation of the abstract see Supplementary Materials section.


Assuntos
Fibrilação Atrial/fisiopatologia , Isquemia Encefálica/fisiopatologia , AVC Isquêmico/fisiopatologia , Monitorização Fisiológica/métodos , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Eletrocardiografia/métodos , Feminino , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
6.
J Neurooncol ; 152(3): 483-490, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33674992

RESUMO

PURPOSE: Patients with glioblastoma (GBM) or brain metastases (MET) and atrial fibrillation (AF) might be at an increased risk of intracranial hemorrhage (ICH) due to anticoagulation (AC). Our aim was to assess this risk. METHODS: Our institution's database (from 2005 to 2017) was screened for patients with GBM or MET and AF with an indication for AC according to their CHA2DS2VASc stroke risk score (≥ 2). Required follow-up was at least 3 months. AC was either performed with heparins, phenprocoumon or non-Vitamin K antagonist oral anticoagulants. Applying the propensity score approach, patient cohorts (matched according to primary tumor, age, sex) were generated (GBM [or MET] with AF ± AC, GBM [or MET] without AF/AC, no GBM [or MET] but AF on AC). ICH was defined as clinical deterioration caused by new blood on imaging. A log rank test was performed to compare the risk for ICH between the three groups. RESULTS: In total, 104 patients were identified of which 49 with GBM (37% on AC) and 37 with MET (46% on AC) were successfully matched. Median follow up was 8.6 and 7.2 months, respectively. ICH occurred in 10.2% of GBM + AF and 12.2% GBM-AF, whereas 8% of patients with AF on AC suffered ICH (p = 0.076). 13.5% of patients with MET + AF had ICHs, in the controls it was 16% for MET-AF and 8% for AF on AC (p = 0.11). CONCLUSION: AC did not seem to influence the incidence of ICH in patients with glioblastoma or brain metastases within follow up of just under 9 months.

7.
J Clin Neurosci ; 79: 197-202, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33070895

RESUMO

OBJECTIVE: Administration of prothrombin complex concentrate (PCC) is recommended for vitamin K antagonist (VKA) reversal in patients with severe bleeding complications. However, there are only limited data available on its use for VKA reversal in patients with traumatic intracranial hemorrhage (ICH). METHODS: Data from all anticoagulated patients referred to our hospital for treatment of traumatic ICH and who received PCC for anticoagulation reversal were retrospectively analysed with specific focus on bleeding and thromboembolic complications during the further in-hospital course. RESULTS: A total of 142 patients were included in the present study. The median age was 78 years (Interquartile range [IQR]: 72-84) and the median Glasgow Coma Scale (GCS) score on admission was 12 (IQR: 7-14). Median International Normalized Ratio (INR) on admission was 2.5 [IQR: 2.0-3.3] and decreased to 1.2 [IQR: 1.1-1.3] following administration of a median dose of 2000 I.U. PCC [IQR: 1500-2625]. The in-hospital mortality rate was 13% and the median GCS of survivors at discharge was 14 [IQR: 12-15]. Thromboembolic events after PCC administration occurred in 4 patients (2.8%). The overall one-year mortality rate in this patient cohort was 49%. CONCLUSIONS: PCC administration rapidly normalises INR and facilitates urgent neurosurgical procedures in anticoagulated patients with traumatic ICH.


Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia Intracraniana Traumática/tratamento farmacológico , Idoso , Anticoagulantes/efeitos adversos , Coagulação Sanguínea , Fatores de Coagulação Sanguínea/administração & dosagem , Feminino , Escala de Coma de Glasgow , Humanos , Hemorragia Intracraniana Traumática/sangue , Hemorragia Intracraniana Traumática/patologia , Pessoa de Meia-Idade , Resultado do Tratamento
8.
J Psychosom Res ; 137: 110205, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32768689

RESUMO

OBJECTIVE: Transient ischemic attack (TIA) has been reported to be frequently followed by symptoms of post-TIA posttraumatic stress disorder (post-TIA PTSD). Risk factors for post-TIA PTSD remain largely unknown. We aimed to identify predictors of post-TIA PTSD development to enable post-TIA PTSD risk assessment and inform future development of treatment and prevention interventions. METHOD: TIA patients were examined twice for this observational cohort study. Symptoms of post-TIA PTSD, depression and anxiety were assessed shortly after TIA during in-hospital stay (T1) and three months after TIA (T2). The impact of known general PTSD risk factors (psychiatric history, peritraumatic dissociation, social support), psychological resilience factors (sense of coherence, mindfulness, attachment style) and TIA characteristics (affected circulatory territory, symptom type and duration) at T1 on post-TIA PTSD symptom severity at T2 was tested using hierarchical multiple linear regression. RESULTS: Sixty-one patients (83.6%) completed the study at T2. Fifteen patients (24.6%) were classified as post-TIA PTSD⊕ at T2. In multiple linear regression analysis, age, sex, psychiatric history, peritraumatic dissociation and social support together explained 39.9% of variance of post-TIA posttraumatic stress symptom severity. Sense of coherence and mindfulness explained further 17.8% of variance. Clinical TIA characteristics were not associated with post-TIA PTSD. CONCLUSIONS: Post-TIA PTSD is a common phenomenon. General PTSD risk factors can be applied for post-TIA PTSD risk assessment. Sense of coherence and mindfulness are promising target variables for post-TIA PTSD treatment and prevention interventions.

9.
JAMA ; 322(14): 1392-1403, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31593272

RESUMO

Importance: The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established. Objective: To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH. Design, Setting, and Participants: Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015). Exposure: Surgical hematoma evacuation vs conservative treatment. Main Outcomes and Measures: The primary outcome was functional disability evaluated by the modified Rankin Scale ([mRS] score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS, 4-6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH. Results: Among 578 patients with cerebellar ICH, propensity score-matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm3 vs 18.8 cm3). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio [AOR], 0.94 [95% CI, 0.81 to 1.09], P = .43; adjusted risk difference [ARD], -3.7% [95% CI, -8.7% to 1.2%]) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 [95% CI, 1.07 to 1.45], P = .005; ARD, 18.5% [95% CI, 13.8% to 23.2%]) and at 12 months (71.7% vs 57.2%; AOR, 1.21 [95% CI, 1.03 to 1.42], P = .02; ARD, 17.0% [95% CI, 11.5% to 22.6%]). A volume range of 12 to 15 cm3 was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume ≤12 cm3, 30.6% vs 62.3% [P = .003]; ARD, -34.7% [-38.8% to -30.6%]; P value for interaction, .01), and above, it was associated with greater likelihood of survival (volume ≥15 cm3, 74.5% vs 45.1% [P < .001]; ARD, 28.2% [95% CI, 24.6% to 31.8%]; P value for interaction, .02). Conclusions and Relevance: Among patients with cerebellar ICH, surgical hematoma evacuation, compared with conservative treatment, was not associated with improved functional outcome. Given the null primary outcome, investigation is necessary to establish whether there are differing associations based on hematoma volume.


Assuntos
Doenças Cerebelares/cirurgia , Hemorragia Cerebral/cirurgia , Tratamento Conservador , Hematoma/cirurgia , Idoso , Doenças Cerebelares/terapia , Cerebelo/cirurgia , Hemorragia Cerebral/terapia , Feminino , Hematoma/terapia , Humanos , Masculino , Estudos Observacionais como Assunto , Resultado do Tratamento
10.
BMC Pharmacol Toxicol ; 20(1): 53, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464657

RESUMO

BACKGROUND: Apixaban effectively lowers the risk of ischemic stroke and systemic embolism in patients with non-valvular atrial fibrillation. Systemic exposure to a given apixaban dose depends on multiple clearance pathways. Though routine quantification of direct oral anticoagulants (DOACs) in neurological emergency situations has not been widely established, suspected associations of DOAC peak concentrations with bleeding events and DOAC trough concentrations with efficacy and safety suggest that such information might support clinical decision making. CASE PRESENTATION: We describe the case of a 75 year-old woman with atrial fibrillation maintained on apixaban who was admitted due to suspected acute stroke. Clinical work-up did not confirm ischemic or hemorrhagic stroke but routine quantification of apixaban revealed an excessively high apixaban plasma concentration (~ 3 h after the last drug intake: 1100 ng/ml (expected range: 91-321 ng/ml); ~ 12 h after drug intake: 900 ng/ml (expected range: 41-230 ng/ml)) and a substantially prolonged elimination half-life (~ 31 h). The corresponding apixaban concentration-to-dose ratio was 9900 (ng/ml)/(mg/kg/d) and 8100 (ng/ml)/(mg/kg/d), respectively (expected range: 249-463 (ng/ml)/(mg/kg/d)). Renal function was only moderately impaired (creatinine 1.36 mg/dl (0.5-1.1 mg/dl), creatinine clearance 40 ml/min). Genotype analyses revealed that the patient was a CYP3A5*3/*3 non-expressor, a heterozygous carrier of the ABCG2 c.421C/A alleles, and a homozygous carrier of ABCB1 c.2677 T/T and ABCB1 c.3435 T/T. In the absence of known drug interactions explaining apixaban clearance impairment, excessive apixaban concentrations were most probably caused by moderate renal impairment combined with multiple functional polymorphisms of apixaban clearance pathways. CONCLUSIONS: This case suggests that concurrent genetic polymorphisms can impair multiple apixaban elimination pathways and thus substantially increase its exposure.


Assuntos
Anticoagulantes/farmacocinética , Polimorfismo Genético , Pirazóis/farmacocinética , Piridonas/farmacocinética , Idoso , Anticoagulantes/sangue , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Feminino , Humanos , Pirazóis/sangue , Pirazóis/uso terapêutico , Piridonas/sangue , Piridonas/uso terapêutico
11.
Eur Stroke J ; 4(2): 181-188, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31259266

RESUMO

Background: Anticoagulation with vitamin K antagonists and non-vitamin K antagonists oral anticoagulants (NOAC) is effective in stroke prevention in patients with atrial fibrillation. However, anticoagulation also poses a major challenge for emergency treatment of patients suffering ischaemic stroke or intracerebral haemorrhage. Aim: The registry RASUNOA-prime is designed to describe current patterns of emergency management, clinical course and outcome of patients with atrial fibrillation experiencing an acute ischaemic stroke or intracerebral haemorrhage under different anticoagulation schemes prior to stroke (NOAC, vitamin K antagonists or no anticoagulation). Methods and design: RASUNOA-prime (ClinicalTrials.gov, NCT02533960) is a prospective, investigator-initiated, multicentre, observational cohort study aiming to recruit 3000 patients with acute ischaemic stroke and atrial fibrillation, and 1000 patients with acute intracerebral haemorrhage and atrial fibrillation with different anticoagulation schemes pre-stroke. It is a non-interventional triple-armed study aiming at a balanced inclusion of ischaemic stroke and intracerebral haemorrhage patients according to the different anticoagulation schemes. Patients will be followed up for clinical course, management and outcome up to three months after the event. Findings in ischaemic stroke and intracerebral haemorrhage patients on NOAC will be compared with patients taking vitamin K antagonists or no anticoagulant pre-stroke. Study outcomes: Primary endpoint for ischaemic stroke patients: occurrence of symptomatic intracerebral haemorrhage, for intracerebral haemorrhage patients: occurrence of secondary haematoma expansion. Secondary endpoints include assessment of coagulation, use of thrombolysis and/or mechanical thrombectomy, occurrence of complications, implementation of secondary prevention. Summary: Describing the current patterns of early management as well as outcome of stroke patients with atrial fibrillation will help guide physicians to develop recommendations for emergency treatment of stroke patients under different anticoagulation schemes.

12.
Stroke ; 50(6): 1392-1402, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31092170

RESUMO

Background and Purpose- Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established. Methods- Multicenter observational cohort study integrating individual patient data of 1328 patients with oral anticoagulation-associated ICH, including 190 NOAC-related ICH patients, recruited from 2011 to 2015 at 19 tertiary centers across Germany. Imaging, clinical characteristics, and 3-months modified Rankin Scale (mRS) outcomes were compared in NOAC- versus VKA-related ICH patients. Propensity score matching was conducted to adjust for clinically relevant differences in baseline parameters. Subgroup analyses were performed regarding NOAC agent, dosing and present clinically relevant anticoagulatory activity (last intake <12h/24h or NOAC level >30 ng/mL). Results- Despite older age in NOAC patients, there were no relevant differences in clinical and hematoma characteristics between NOAC- and VKA-related ICH regarding baseline hematoma volume (median [interquartile range]: NOAC, 14.7 [5.1-42.3] mL versus VKA, 16.4 [5.8-40.6] mL; P=0.33), rate of hematoma expansion (NOAC, 49/146 [33.6%] versus VKA, 235/688 [34.2%]; P=0.89), and the proportion of patients with unfavorable outcome at 3 months (mRS, 4-6: NOAC 126/179 [70.4%] versus VKA 473/682 [69.4%]; P=0.79). Subgroup analyses revealed that NOAC patients with clinically relevant anticoagulatory effect had higher rates of intraventricular hemorrhage (n/N [%]: present 52/109 [47.7%] versus absent 9/35 [25.7%]; P=0.022) and hematoma expansion (present 35/90 [38.9%] versus absent 5/30 [16.7%]; P=0.040), whereas type of NOAC agent or different NOAC-dosing regimens did not result in relevant differences in imaging characteristics or outcome. Conclusions- If effectively anticoagulated, there are no differences in hematoma characteristics and functional outcome among patients with NOAC- or VKA-related ICH. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03093233.


Assuntos
Anticoagulantes/administração & dosagem , Hemorragia Cerebral/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Vitamina K/antagonistas & inibidores , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Estudos Retrospectivos
13.
J Neurol Neurosurg Psychiatry ; 90(7): 783-791, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30992334

RESUMO

OBJECTIVE: To determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH. METHODS: Retrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC. RESULTS: IHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04-1.93) vs non-LDSH: 1.32 (0.33-3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38-4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4-6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume <4.4 mL: 0.18 (0.04-0.78); p=0.022) and low National Institutes of Health Stroke Scale (NIHSS) score on admission (OR: NIHSS <4: 0.29 (0.11-0.78); p=0.014) were significantly associated with fewer IHC. CONCLUSIONS: Heparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention.


Assuntos
Hemorragia Cerebral/complicações , Heparina/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/mortalidade , Feminino , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/mortalidade
14.
Cerebrovasc Dis ; 47(1-2): 48-56, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30783049

RESUMO

BACKGROUND AND PURPOSE: Renal dysfunction (RD) is overall associated with unfavorable functional outcome and higher risk of mortality after acute ischemic stroke. Associations between RD and outcome in patients with acute vertebrobasilar stroke treated with thrombectomy have not been evaluated so far. MATERIALS AND METHODS: Consecutive patients with vertebrobasilar stroke treated with mechanical thrombectomy between October 2010 and July 2017 at our center were analyzed. RD was defined as glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 at admission. Endpoints were (I) poor clinical outcome (modified Rankin Scale > 2) at 3 months, (II) 3-month mortality, and (III) intracerebral hemorrhage (ICH) after treatment. RESULTS: Overall, 106 patients were included. Median age was 73.0 years (interquartile range 62.0-80.0), and RD was present in 20.8%. Multivariate analysis revealed that RD was associated with a higher risk for any ICH (OR 3.54; 95% CI 1.09-11.49; p = 0.035). Stroke severity at onset predicted poor clinical outcome (OR 1.08; 95% CI 1.03-1.14; p = 0.003). Neither low GFR nor any ICH, but stroke severity (OR 1.08; 95% CI 1.03-1.14; p = 0.002) and poor recanalization results (OR 11.38; 95% CI 2.01-64.41; p = 0.006) were associated with a higher risk for mortality. CONCLUSIONS: Patients with RD and acute vertebrobasilar stroke should be thoroughly monitored to prevent ICH after thrombectomy. Our results support performing mechanical thrombectomy in acute stroke patients with large vessel occlusions of the posterior circulation, irrespective of their renal function.


Assuntos
Hemorragia Cerebral/etiologia , Taxa de Filtração Glomerular , Nefropatias/complicações , Rim/fisiopatologia , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversos , Insuficiência Vertebrobasilar/cirurgia , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/diagnóstico por imagem , Bases de Dados Factuais , Feminino , Humanos , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento , Insuficiência Vertebrobasilar/complicações , Insuficiência Vertebrobasilar/diagnóstico por imagem
15.
Neurocrit Care ; 30(2): 322-333, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30382531

RESUMO

BACKGROUND: Anticoagulation therapy is a major risk factor for unfavorable patient outcomes following (traumatic) intracranial hemorrhage. Direct oral anticoagulants (DOAC) are increasingly used for the prevention and treatment of thromboembolic diseases. Data on patients treated for acute subdural hemorrhage (SDH) during anticoagulation therapy with DOAC are limited. METHODS: We analyzed the medical records of consecutive patients treated at our institution for acute SDH during anticoagulation therapy with DOAC or vitamin K antagonists (VKA) during a period of 30 months. Patient characteristics such as results of imaging and laboratory studies, treatment modalities and short-term patient outcomes were included. RESULTS: A total of 128 patients with preadmission DOAC (n = 65) or VKA (n = 63) intake were compared. The overall 30-day mortality rate of this patient cohort was 27%, and it did not differ between patients with DOAC or VKA intake (26% vs. 27%; p = 1.000). Similarly, the rates of neurosurgical intervention (65%) and intracranial re-hemorrhage (18%) were comparable. Prothrombin complex concentrates were administered more frequently in patients with VKA intake than in patients with DOAC intake (90% vs. 58%; p < 0.0001). DOAC treatment in patients with acute SDH did not increase in-hospital and 30-day mortality rates compared to VKA treatment. CONCLUSIONS: These findings support the favorable safety profile of DOAC in patients, even in the setting of intracranial hemorrhage. However, the availability of specific antidotes to DOAC may further improve the management of these patients.


Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/administração & dosagem , Hematoma Subdural Agudo/induzido quimicamente , Hematoma Subdural Agudo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Hematoma Subdural Agudo/mortalidade , Humanos , Masculino , Vitamina K/antagonistas & inibidores
16.
Ann Neurol ; 84(5): 694-704, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30255970

RESUMO

OBJECTIVE: Whether intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain. METHODS: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension. RESULTS: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67-1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = -2.83, 95% CI = -5.28 to -0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30-0.84), and smaller baseline hematoma volume (linear regression coefficient = -0.24, 95% CI = -0.47 to -0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm3 (OR = 1.14, 95% CI = 0.81-1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63-1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49-1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57-1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75-1.43). INTERPRETATION: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702-712.


Assuntos
Anticoagulantes/efeitos adversos , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/patologia , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Hemorragia Cerebral/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Vitamina K/antagonistas & inibidores
17.
Anal Chem ; 90(15): 9395-9402, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-29985592

RESUMO

Plasma concentrations of direct oral anticoagulants (DOACs) vary largely between individuals, and they correlate well with desired and adverse outcomes. Although regular concentration monitoring of DOACs is not recommended, information on DOAC exposure could be useful in situations when multiple DOAC-clearance pathways are impaired or nonadherence is suspected. Self-sampling techniques, like the use of dried-blood spots (DBSs), would be particularly useful because they enable the collection of information in ambulatory patients at relevant points in time of the dosing interval (e.g., trough). We developed and validated a DBS-based assay to quantify all currently marketed DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) in a single ultraperformance-liquid-chromatography-tandem-mass-spectrometry assay. It fulfilled all validation standards within a hematocrit range of 0.33-0.65 and was linear over the calibration ranges of 2.5-750 ng/mL (apixaban and rivaroxaban), 4.4-750 ng/mL (dabigatran), and 9.3-750 ng/mL (edoxaban). Only minor ion suppression (matrix effect ≤13%) was present, inter- and intra-assay precision was ≤13%, and inter- and intra-assay accuracies ranged between 88 and 110%. All DOACs were stable in DBSs up to 52 days at room temperature, if the DBSs were protected from light and humidity. The correlation between (whole blood) DBS and plasma concentrations was assessed in 33 patients under regular DOAC therapy. Deming-regression coefficients between simultaneously collected capillary DBSs and plasma samples were used to predict plasma concentrations from DBSs. Bland-Altman plots revealed a strong agreement between predicted and observed plasma concentrations, thus confirming the suitability of DBSs for DOAC monitoring as an important step toward the important aim of self-sampling at home.


Assuntos
Anticoagulantes/sangue , Cromatografia Líquida/métodos , Teste em Amostras de Sangue Seco/métodos , Espectrometria de Massas em Tandem/métodos , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/normas , Monitoramento de Medicamentos/métodos , Humanos , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes
18.
Eur Heart J ; 39(19): 1709-1723, 2018 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-29529259

RESUMO

Aims: Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time-window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH. Methods and results: We pooled individual patient-data (n = 2504) from a nationwide multicentre cohort-study (RETRACE, conducted at 22 German centres) and eventually identified MHV-patients (n = 137) with anticoagulation-associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no-TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity-score matching and multivariable cox-regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no-TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no-TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate-ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67-35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA-timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33-21.37; P < 0.01). The hazard for the composite-balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10-5.70; P = 0.03). Conclusion: Restarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing-between least risks for thromboembolic and haemorrhagic complications-provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk.


Assuntos
Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Hemorragia/induzido quimicamente , Tromboembolia/induzido quimicamente , Idoso , Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Hemorragia Cerebral/complicações , Esquema de Medicação , Feminino , Próteses Valvulares Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento , Vitamina K/antagonistas & inibidores
19.
Ann Neurol ; 83(1): 186-196, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29314216

RESUMO

OBJECTIVE: To investigate parameters associated with hematoma enlargement in non-vitamin K antagonist oral anticoagulant (NOAC)-related intracerebral hemorrhage (ICH). METHODS: This retrospective cohort study includes individual patient data for 190 patients with NOAC-associated ICH over a 5-year period (2011-2015) at 19 departments of neurology across Germany. Primary outcome was the association of prothrombin complex concentrate (PCC) administration with hematoma enlargement. Subanalyses were calculated for blood pressure management and its association with the primary outcome. Secondary outcomes include associations with in-hospital mortality and functional outcome at 3 months assessed using the modified Rankin Scale. RESULTS: The study population for analysis of primary and secondary outcomes consisted of 146 NOAC-ICH patients with available follow-up imaging. Hematoma enlargement occurred in 49/146 (33.6%) patients with NOAC-related ICH. Parameters associated with hematoma enlargement were blood pressure ≥ 160mmHg within 4 hours and-in the case of factor Xa inhibitor ICH-anti-Xa levels on admission. PCC administration prior to follow-up imaging was not significantly associated with a reduced rate of hematoma enlargement either in overall NOAC-related ICH or in patients with factor Xa inhibitor intake (NOAC: risk ratio [RR] = 1.150, 95% confidence interval [CI] = 0.632-2.090; factor Xa inhibitor: RR = 1.057, 95% CI = 0.565-1.977), regardless of PCC dosage given or time interval until imaging or treatment. Systolic blood pressure levels < 160mmHg within 4 hours after admission were significantly associated with a reduction in the proportion of patients with hematoma enlargement (RR = 0.598, 95% CI = 0.365-0.978). PCC administration had no effect on mortality and functional outcome either at discharge or at 3 months. INTERPRETATION: In contrast to blood pressure control, PCC administration was not associated with a reduced rate of hematoma enlargement in NOAC-related ICH. Our findings support the need of further investigations exploring new hemostatic reversal strategies for patients with factor Xa inhibitor-related ICH. Ann Neurol 2018;83:186-196.


Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/efeitos adversos , Hemorragia Cerebral/patologia , Hematoma/patologia , Idoso , Idoso de 80 Anos ou mais , Fatores de Coagulação Sanguínea/uso terapêutico , Pressão Sanguínea , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/mortalidade , Estudos de Coortes , Fator Xa , Feminino , Alemanha/epidemiologia , Hematoma/induzido quimicamente , Hematoma/mortalidade , Hemostáticos/uso terapêutico , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
20.
J Pharm Biomed Anal ; 148: 238-244, 2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29055248

RESUMO

Direct oral anticoagulants (DOACs) are among the most effective options to prevent serious thromboembolic events in patients with atrial fibrillation. Coagulation assays are used to assess DOAC activity, but lack the possibility to quantify drugs with concurrent pharmacodynamic effect. We developed a selective multi-drug assay to analyze apixaban, betrixaban, dabigatran, edoxaban, edoxaban M4, and rivaroxaban with ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC/MS/MS) in plasma fulfilling all requirements of the FDA und EMA guidelines for bioanalytical method validation. Plasma samples were extracted using solid phase extraction in a 96-well micro volume format. Chromatographic separation was performed on a Waters BEH Phenyl 1.7µm column coupled to tandem mass spectrometry. Extraction recoveries exceeded 80 %. Concentrations of 1-1000 ng/ml can be precisely quantified (correlation coefficient of >0.99) using 100 µL plasma volume. Intra-day and inter-day accuracies ranged between 91.0 % and 116 %. Precisions at low and high concentrations were below 13.3 %. The method was applied within a clinical drug trial and eight short pharmacokinetic profiles of patients under DOAC therapy were analyzed. The assay allows for highly sensitive and selective simultaneous quantification of DOACs in patient plasma samples.


Assuntos
Anticoagulantes/sangue , Anticoagulantes/química , Administração Oral , Coagulação Sanguínea/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos
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