Safety of endovascular treatment in acute stroke patients taking oral anticoagulants.

Background The endovascular treatment of acute cerebral ischemia has been proven beneficial without major safety concerns. To date, the role of endovascular treatment in patients treated with oral anticoagulants, which may be associated with periprocedural intracranial bleeding, remains uncertain. Aims The objective of the current analysis is to evaluate the safety of endovascular treatment in patients treated with oral anticoagulants. Methods The ENDOSTROKE-Registry is a commercially independent, prospective observational study in 12 stroke centers in Germany and Austria collecting pre-specified variables about endovascular stroke therapy. Results Data from 815 patients (median age 70 (interquartile range (IQR) 20), 57% male) undergoing endovascular treatment with known anticoagulation status were analyzed. A total of 85 (median age 76 (IQR 8), 52% male) patients (10.4%) took vitamin-K-antagonists prior to endovascular treatment. Anticoagulation status as measured with international normalized ratio was above 2.0 in 31 patients. Intracranial hemorrhage occurred in 11.8% of patients taking vitamin-K-antagonists compared to no-vitamin-K-antagonists (12.2%, p = 0.909). After adjustment for confounding factors which were unbalanced at univariate level such as NIHSS and age, anticoagulation status was not found to significantly influence clinical outcome (modified Rankin Scale 3-6) and occurrence of intracranial hemorrhage in a multivariate logistic regression analysis. Conclusion Prior use of vitamin-K-antagonists was not associated with a higher rate of periprocedural intracranial hemorrhage after endovascular treatment or worse outcome. Endovascular treatment should be considered as an important treatment option in patients taking vitamin-K-antagonists.

Intravenous Thrombolysis With Recombinant Tissue-Type Plasminogen Activator in a Stroke Patient Receiving Dabigatran Anticoagulant After Antagonization With Idarucizumab.

BACKGROUND AND PURPOSE: Therapeutic options for acute ischemic stroke patients presenting on effective anticoagulation are limited. Idarucizumab, a humanized, monoclonal antibody fragment for immediate reversal of dabigatran, may allow this subgroup of orally anticoagulated patients to regain eligibility for thrombolysis. METHODS: We report the first successful acute antagonization of dabigatran by idarucizumab before intravenous thrombolysis with recombinant tissue-type plasminogen activator. RESULTS: Idarucizumab was given to a 76-year-old male patient on dabigatran ≈3.5 hours after his last dose. Neurological status on admission was NIHSS (National Institutes of Health Stroke Scale) 11. Recombinant tissue-type plasminogen activator was initiated immediately after dabigatran reversal. The patient was discharged with a favorable outcome of NHISS 1 on day 7. No complications were observed. CONCLUSIONS: This case represents a new therapeutic paradigm. It is further supported by in vitro data showing no nonspecific interactions of idarucizumab with recombinant tissue-type plasminogen activator-induced thrombolysis. Thus, patients effectively anticoagulated with dabigatran who were previously contraindicated for thrombolytic therapy in this situation may now receive treatment because of the ability to rapidly reverse the anticoagulant activity of dabigatran with idarucizumab.

Collateral vessels in proximal middle cerebral artery occlusion: the ENDOSTROKE study.

PURPOSE: To determine the impact of collateral vessel status on clinical and imaging outcomes in patients undergoing endovascular therapy (EVT) for proximal middle cerebral artery (MCA) occlusion. MATERIALS AND METHODS: There were 160 patients with proximal MCA occlusion at six centers in this institutional review board-approved multicenter EVT registry. Angiograms were analyzed at a blinded core laboratory, and collateral vessel status was assessed by using the American Society of Interventional and Therapeutic Neuroradiology (ASITN)/Society of Interventional Radiology (SIR) collateral vessel grading system, while reperfusion was assessed by using the Thrombolysis in Cerebral Infarction (TICI) scale. Good outcome was defined as a modified Rankin Scale score of 0-2 at follow-up. Binary logistic regression analysis was performed by using parameters with P < .2 in univariate analysis. RESULTS: Good clinical outcome was attained in 62 (39%) of the 160 patients, and TICI 2b-3 reperfusion was achieved in 94 (59%) patients. Nineteen patients had ASITN/SIR collateral vessel grades of 0 or 1, 63 patients had a grade of 2, and 78 patients had grades of 3 or 4. Better collateral vessels were associated with higher reperfusion rates (21%, 48%, and 77% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P < .001), a higher proportion of infarcts smaller than one-third of the MCA territory (32%, 48%, and 69% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P < .001), and a higher proportion of good clinical outcome (11%, 35%, and 49% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P = .007). At multivariable analysis, collateral vessel status independently predicted reperfusion, final infarct size, and clinical outcome. Within an onset-to-treatment time (OTT) of 0-3 hours, collateral vessel status predicted final infarct size and reperfusion. Within an OTT of 3-6 hours, it additionally predicted clinical outcome, with 53% of patients with ASITN/SIR grades of 3 or 4 having a good outcome, as compared with 0% of patients with grades of 0 or 1 and 27% of patients with a grade of 2 (P = .008). CONCLUSION: In this patient population, collateral vessel status independently predicted the pivotal outcome parameters of reperfusion, infarct size, and clinical outcome. These data underscore the utility of patient selection for EVT on the basis of collateral vessel status.

Mechanical recanalization in basilar artery occlusion: the ENDOSTROKE study.

OBJECTIVE: A study was undertaken to evaluate clinical and procedural factors associated with outcome and recanalization in endovascular stroke treatment (EVT) of basilar artery (BA) occlusion. METHODS: ENDOSTROKE is an investigator-initiated multicenter registry for patients undergoing EVT. This analysis includes 148 consecutive patients with BA occlusion, with 59% having received intravenous thrombolysis prior to EVT. Recanalization (defined as Thrombolysis in Cerebral Infarction [TICI] score 2b-3) and collateral status (using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology collateral grading system) were assessed by a blinded core laboratory. Good (moderate) outcome was defined as a modified Rankin Scale score of 0 to 2 (0-3) assessed after at least 3 months (median time to follow-up = 120 days). RESULTS: Thirty-four percent had good and 42% had moderate clinical outcome; mortality was 35%. TICI 2b-3 recanalization was achieved by 79%. Age, hypertension, National Institutes of Health Stroke Scale scores, collateral status, and the use of magnetic resonance imaging prior to EVT predicted clinical outcome, the latter 3 remaining independent predictors in multivariate analysis. Independent predictors of recanalization were better collateral status and the use of a stent retriever. However, recanalization did not significantly predict clinical outcome. INTERPRETATION: Beside initial stroke severity, the collateral status predicts clinical outcome and recanalization in BA occlusion. Our data suggest that the use of a stent retriever is associated with high recanalization rates, but recanalization on its own does not predict outcome. The role of other modifiable factors, including the choice of pretreatment imaging modality and time issues, warrants further investigation.

Age dependency of successful recanalization in anterior circulation stroke: the ENDOSTROKE study.

BACKGROUND: Clinical outcome after endovascular stroke therapy (EVT) for proximal anterior circulation stroke is often disappointing despite high recanalization rates. The ENDOSTROKE study aims to determine predictors of clinical outcome in patients undergoing EVT. Here we focus on the impact of age and recanalization on proximal middle cerebral artery (M1-MCA) or carotid T occlusion. METHODS: ENDOSTROKE is an investigator-initiated, industrially independent multicenter registry launched in January, 2011, for consecutive patients undergoing EVT for large-vessel stroke. This analysis focuses on patients treated in 11 academic and nonacademic stroke centers with angiographically proven M1-MCA (n = 259) or carotid T occlusion (n = 103). Recanalization was defined as Thrombolysis in Myocardial Infarction (TIMI) score 2 or 3, and in patients with available Thrombolysis in Cerebral Ischemia (TICI) data (n = 309) as TICI scores 2b-3. Good outcome was defined as modified Rankin Scale (mRS) score of 0-2 assessed after 3 months or later. RESULTS: The median age was 68 years (25th and 75th percentiles: 56, 76 years), and the median National Institutes of Health Stroke Scale (NIHSS) score at admission was 16 (13, 19); 41% of the patients had a favorable (mRS scores 0-2), and 59% had an unfavorable (mRS scores 3-6) outcome; 83% reached TIMI 2-3 flow. Independent predictors of good outcome were younger age, lower initial NIHSS scores, TIMI 2/3 recanalization and lower serum glucose levels. Outcome was highly dependent on patients' age: 60% of the patients within the lowest age quartile (range: 18-56 years) experienced good clinical outcome, decreasing stepwise over 47% (57-68 years) and 37% (69-76 years) to 17% in the highest age quartile (77-94 years). The proportion of patients with poor clinical outcome despite TIMI 2/3 recanalization ('futile recanalization') increased dramatically from only 29% in the lowest age quartile over 34% and 40% (2nd and 3rd age quartiles) up to 53% in the highest age quartile. Results were similar in patients with available TICI scores, with 'futile recanalization' rates increasing from 24% to 46% (lowest to highest age quartile). CONCLUSIONS: This study emphasizes the dramatic impact of patients' age on outcome in EVT for M1-MCA or carotid T occlusion, even in the presence of recanalization. Reasons for this age-related decrease in clinically successful recanalization rates urgently need clarification and may comprise patient-related factors (age-related increase in cardioembolic strokes, collateral status, comorbidities) as well as periprocedural issues (tortuous vessel anatomy in the elderly, age-dependent negative impact of general anesthesia in EVT).

Periprocedural aspects in mechanical recanalization for acute stroke: data from the ENDOSTROKE registry.

INTRODUCTION: The ENDOSTROKE registry aims to accompany the spreading use of endovascular stroke treatment (EVT) in academic and non-academic hospitals. This analysis focuses on preprocedural imaging, patient handling and referral, as well as on different treatment modalities in mechanical recanalization. METHODS: Data for this study were from observational registry study in 12 stroke centers in Germany and Austria with online assessment of prespecified variables concerning endovascular stroke therapy. RESULTS: Data from 734 patients undergoing EVT were analyzed. Preferred imaging modality prior to EVT was CT (83 %) and CTA (78 %). In 95 %, EVT was performed under general anesthesia. In 55 % of patients, a combination of intravenous (IV) thrombolysis and EVT was used, followed by pure EVT (25 %), intra-arterial (IA) thrombolysis plus EVT (13 %) and IV + IA thrombolysis plus EVT (7 %). Intrahospital time delay until start of EVT was 91 and 99 min in anterior and vertebrobasilar circulation stroke, respectively. Average duration of EVT was 60 min. Overall thrombolysis in myocardial infarction grade 2/3 recanalization rate was 85 %. Stent retrievers were used in 75 %, being associated with higher recanalization rates than non-stent retrievers. Hemorrhagic complications (symptomatic and asymptomatic) occurred in 12 %. Overall vessel occlusion time was approximately 60 min longer in patients being referred from a primary care hospital for EVT. CONCLUSION: This study gives an overview of procedure-related factors in current EVT practice. It gives estimates on preprocedural imaging modalities, periprocedural handling, and treatment combinations used for EVT. Patient referral for EVT from primary care hospitals is associated with longer vessel occlusion times.

Infection after acute ischemic stroke: risk factors, biomarkers, and outcome.

Background. The activation of inflammatory cascades triggered by ischemic stroke may play a key role in the development of infections. Methods. Patients admitted with ischemic stroke within 24 hours were prospectively enrolled. Biomarkers of infection were measured on days 1, 3, and 5. The patients were continuously monitored for predefined infections. Results. Patients with infection were older (OR 1.06 per year, 95% CI 1.01-1.11) and had a higher National Institute of Health Stroke Scale Score (NIHSS, OR 1.21, 95% CI 1.10-1.34), localization in the insula, and higher stroke volumes on diffusion-weighted imaging. The maximum temperature on days 1 and 3, leukocytes, interleukin-6, lipopolysaccharide-binding protein on days 1, 3, and 5, C-reactive protein on days 3 and 5, and procalcitonin on day 5 were higher and HLA-DR-expression on monocytes on days 1, 3, and 5 lower in patients with infection. Age and NIHSS predicted the development of infections. Infection was an independent predictor of poor functional outcome. Conclusions. Severe stroke and increasing age were shown to be early predictors for infections after stroke.