Showing papers on "Thrombolysis published in 2015"

A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study.

Abstract: Objectives This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). Background Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. Methods Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT–measured RV/LV diameter ratio within 48 h of procedure initiation. Results Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, −0.42; p Conclusions Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759 )

Acute Stroke Intervention: A Systematic Review

Abstract: IMPORTANCE Acute ischemic stroke is a major cause of mortality and morbidity in the United States. We review the latest data and evidence supporting catheter-directed treatment for proximal artery occlusion as an adjunct to intravenous thrombolysis in patients with acute

Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis

Abstract: Aim Thrombolytic therapy induces faster clot dissolution than anticoagulation in patients with acute pulmonary embolism (PE) but is associated with an increased risk of haemorrhage. We reviewed the risks and benefits of thrombolytic therapy in the management of patients with acute PE. Methods and results We systematically reviewed randomized controlled studies comparing systemic thrombolytic therapy plus anticoagulation with anticoagulation alone in patients with acute PE. Fifteen trials involving 2057 patients were included in our meta-analysis. Compared with heparin, thrombolytic therapy was associated with a significant reduction of overall mortality (OR; 0.59, 95% CI: 0.36–0.96). This reduction was not statistically significant after exclusion of studies including high-risk PE (OR; 0.64, 95% CI: 0.35–1.17). Thrombolytic therapy was associated with a significant reduction in the combined endpoint of death or treatment escalation (OR: 0.34, 95% CI: 0.22–0.53), PE-related mortality (OR: 0.29; 95% CI: 0.14–0.60) and PE recurrence (OR: 0.50; 95% CI: 0.27–0.94). Major haemorrhage (OR; 2.91, 95% CI: 1.95–4.36) and fatal or intracranial bleeding (OR: 3.18, 95% CI: 1.25–8.11) were significantly more frequent among patients receiving thrombolysis. Conclusions Thrombolytic therapy reduces total mortality, PE recurrence, and PE-related mortality in patients with acute PE. The decrease in overall mortality is, however, not significant in haemodynamically stable patients with acute PE. Thrombolytic therapy is associated with an increase of major and fatal or intracranial haemorrhage.

Mechanical recanalization in basilar artery occlusion: The ENDOSTROKE study

Abstract: 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. Ann Neurol 2015;77:415–424

Solitaire™ with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial: protocol for a randomized, controlled, multicenter study comparing the Solitaire revascularization device with IV tPA with IV tPA alone in acute ischemic stroke.

Abstract: RATIONALE Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions. AIM The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke. DESIGN The study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled. PROCEDURES Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset. STUDY OUTCOMES The primary end-point is 90-day global disability, assessed with the modified Rankin Scale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure. ANALYSIS Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale (Rankin shift) and proportions of subjects achieving functional independence (mRS 0-2).

Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study

Abstract: Summary Background In most countries, alteplase given within 4·5 h of onset is the only approved medical treatment for acute ischaemic stroke. The newer thrombolytic drug tenecteplase has been investigated in one randomised trial up to 3 h after stroke and in another trial up to 6 h after stroke in patients selected by advanced neuroimaging. In the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST), we aimed to assess the efficacy and safety of tenecteplase versus alteplase within 4·5 h of stroke onset in a population not selected on the basis of advanced neuroimaging, and to use imaging biomarkers to inform the design of a definitive phase 3 clinical trial. Methods In this single-centre, phase 2, prospective, randomised, open-label, blinded end-point evaluation study, adults with supratentorial ischaemic stroke eligible for intravenous thrombolysis within 4·5 h of onset were recruited from The Institute of Neurological Sciences, Glasgow, Scotland. Patients were randomly assigned (1:1) to receive tenecteplase 0·25 mg/kg (maximum 25 mg) or alteplase 0·9 mg/kg (maximum 90 mg). Treatment allocation used a mixed randomisation and minimisation algorithm including age and National Institutes of Health Stroke Scale score, generated by an independent statistician. Patients were not informed of treatment allocation; treating clinicians were aware of allocation but those assessing the primary outcome were not. Imaging comprised baseline CT, CT perfusion, and CT angiography; and CT plus CT angiography at 24–48 h. The primary endpoint was percentage of penumbra salvaged (CT perfusion-defined penumbra volume at baseline minus CT infarct volume at 24–48 h). Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT01472926. Findings Between Jan 1, 2012, and Sept 7, 2013, 355 patients were screened, of whom 157 were eligible for intravenous thrombolysis, and 104 patients were enrolled. 52 were assigned to the alteplase group and 52 to tenecteplase. Of 71 patients (35 assigned tenecteplase and 36 assigned alteplase) contributing to the primary endpoint, no significant differences were noted for percentage of penumbral salvaged (68% [SD 28] for the tenecteplase group vs 68% [23] for the alteplase group; mean difference 1·3% [95% CI −9·6 to 12·1]; p=0·81). Neither incidence of symptomatic intracerebral haemorrhage (by SITS-MOST definition, 1/52 [2%] tenecteplase vs 2/51 [4%] alteplase, p=0·55; by ECASS II definition, 3/52 [6%] vs 4/51 [8%], p=0·59) nor total intracerebral haemorrhage events (8/52 [15%] vs 14/51 [29%], p=0·091) differed significantly. The incidence of serious adverse events did not differ between groups (32 in the tenecteplase group, three considered probably or definitely related to drug treatment; 16 in the alteplase group, five were considered drug-related). Interpretation Neurological and radiological outcomes did not differ between the tenecteplase and alteplase groups. Evaluation of tenecteplase in larger trials of patients with acute stroke seems warranted. Funding The Stroke Association.

Collateral Circulation in Ischemic Stroke: Assessment Tools and Therapeutic Strategies

Abstract: Revascularization encompasses all treatment-related improvements in blood flow, including recanalization of the proximal arterial occlusion and reperfusion of the downstream territory. Recanalization is required for antegrade tissue reperfusion, but recanalization may not necessarily lead to reperfusion in regions where distal emboli or established infarctions are present.1,2 On the contrary, acute reperfusion without recanalization may occur in patients who received or did not received endovascular therapies, and reperfusion ≤6 hours was consistently superior to recanalization in predicting tissue and clinical outcome.3 The cerebral collateral circulation refers to the subsidiary network of vascular channels that stabilize cerebral blood flow when principal conduits fail. Collateral status differs among patients with acute ischemic stroke. Relatively sparse attention has been devoted to the role of baseline collateral circulation in patients with acute ischemic stroke who are candidates for revascularization. The Interventional Management of Stroke (IMS) III,4 Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE),5 and Intra-Arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS EXP) trials6 were 3 multicenter, prospective, randomized controlled trials, which failed to show a benefit from endovascular intervention for acute ischemic stroke. In addition, successful recanalization failed to improve the functional outcome in a significant proportion of patients, ranging from 26% to 49% (futile and dangerous recanalization), stimulating the need to improve the selection of patients based on individual pathophysiology.7,8 Among neuroimaging parameters, a large core and poor collaterals are demonstrated to be strong predictors of both response to endovascular therapy and functional outcome,9–13 and excluding patients with large core and poor collateral circulation may improve the therapeutic benefit from endovascular therapy. In the subgroup analysis of the IMS III trial, more robust collateral grade was associated with better clinical outcomes.14 Adequate collateral circulation …

Thrombolysis in Pediatric Stroke Study

Abstract: Stroke is an important acute neurological condition in children with an annual incidence ranging from 2.3 to 13 per 100 000 children.1–3 Although most children who experience stroke do not die of the acute disorder, the consequences of the brain injury are amortized during the lengthy life span that follows.4–8 The reduction potential in lifelong morbidity by timely and effective intervention with a thrombolytic agent, such as tissue-type plasminogen activator (tPA), in children with acute arterial ischemic stroke (AIS) constituted the core rationale for the study of tPA treatment of acute AIS in children. The perceived high potential for benefit after treatment justified assumption of risk for intracranial hemorrhage (ICH) after its use.9 Because in adults, the risk of hemorrhage after tPA use was thought to be related to infarct volume; this principle was assumed for children. The known developmental trajectory of the fibrinolytic system includes lower levels of endogenous tPA and higher levels of plasminogen activator inhibitor-1 in young children than are found in adults and warranted a dose-finding study beginning at doses lower than that used in adults with incremental increase through the currently used adult dose of 0.9 mg/kg and careful assessment of tPA pharmacokinetics.10 Currently, information on children treated with tPA consists of case reports, small case series, and hospital database documentation. Best practice for the treatment of children with acute stroke has received little rigorous study. Clinical approach varies widely among centers and reflects a dearth of research on which to base treatment protocols. Although tPA is not approved for use in childhood stroke, ≤2% of children with acute stroke are reported to have been treated with tPA in the United States, despite lack of safety and efficacy data.11–14 In 2010, the National Institute …

Effects of Golden Hour Thrombolysis: A Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke (PHANTOM-S) Substudy

Abstract: Importance The effectiveness of intravenous thrombolysis in acute ischemic stroke is time dependent. The effects are likely to be highest if the time from symptom onset to treatment is within 60 minutes, termed the golden hour . Objective To determine the achievable rate of golden hour thrombolysis in prehospital care and its effect on outcome. Design, Setting, and Participants The prospective controlled Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke study was conducted in Berlin, Germany, within an established infrastructure for stroke care. Weeks were randomized according to the availability of a specialized ambulance (stroke emergency mobile unit (STEMO) from May 1, 2011, through January 31, 2013. We included 6182 consecutive adult patients for whom a stroke dispatch (44.1% male; mean [SD] age, 73.9 [15.0] years) or regular care (45.0% male; mean [SD] age, 74.2 [14.9] years) were included. Interventions The STEMO was deployed when the dispatchers suspected an acute stroke during emergency calls. If STEMO was not available (during control weeks, when the unit was already in operation, or during maintenance), patients received conventional care. The STEMO is equipped with a computed tomographic scanner plus a point-of-care laboratory and telemedicine connection. The unit is staffed with a neurologist trained in emergency medicine, a paramedic, and a technician. Thrombolysis was started in STEMO if a stroke was confirmed and no contraindication was found. Main Outcomes and Measures Rates of golden hour thrombolysis, 7- and 90-day mortality, secondary intracerebral hemorrhage, and discharge home. Results Thrombolysis rates in ischemic stroke were 200 of 614 patients (32.6%) when STEMO was deployed and 330 of 1497 patients (22.0%) when conventional care was administered ( P P P = .21 and 0.69 [95% CI, 0.32-1.53]; P = .36) and were more likely to be discharged home (adjusted odds ratio, 1.93 [95% CI, 1.09-3.41]; P = .02). Conclusions and Relevance The use of STEMO increases the percentage of patients receiving thrombolysis within the golden hour. Golden hour thrombolysis entails no risk to the patients’ safety and is associated with better short-term outcomes. Trial Registration clinicaltrials.gov Identifier:NCT01382862

Hypotension During Endovascular Treatment of Ischemic Stroke Is a Risk Factor for Poor Neurological Outcome

Abstract: Background and Purpose—In retrospective studies, patients receiving general anesthesia for endovascular treatment for acute ischemic stroke have worse neurological outcome compared with patients receiving conscious sedation. It has been suggested that this is caused by general anesthesia–associated hypotension. We investigated the effect of intraprocedural hypotension on neurological outcome. Methods—One hundred eight patients with acute ischemic stroke, who underwent endovascular treatment in general anesthesia between 2007 and 2012, were included. Analyzed predictors of neurological outcome were age, sex, comorbidities, baseline National Institutes of Health Stroke Scale, intraprocedural relative changes in mean arterial blood pressure from baseline, blood glucose, modified Thrombolysis in Cerebral Infarction score, and elapsed time from stroke to computed tomography, groin puncture, and recanalization/end of procedure. Results—A fall in mean arterial blood pressure of >40% was an independent predictor ...

Intravenous Fibrinolytic Therapy in Central Retinal Artery Occlusion A Patient-Level Meta-analysis

Abstract: Importance Central retinal artery occlusion (CRAO) is an ophthalmologic emergency that can result in blindness At present, no proven therapy for CRAO exists Treatment with fibrinolytic agents has shown promise but remains of unproven benefit Objectives To assess the efficacy of systemic fibrinolytic therapy for patients with CRAO and to define a time window of efficacy Data Sources We systematically queried PubMed, Web of Science, and Scopus using the following index terms: “retinal artery occlusion” OR “retinal ischemia” AND “thrombolysis” OR “fibrinolysis” OR “tissue plasminogen activator” OR “streptokinase” OR “urokinase” Search was not limited by year of publication or language and was conducted in August 2014 In addition, we evaluated the references from relevant review articles Study Selection We assembled observational studies reporting on visual acuity outcomes after CRAO Inclusion criteria were complete reporting of visual outcomes after CRAO (with or without fibrinolytic therapy) and a series of more than 5 patients for fibrinolysis treatment or more than 20 cases when untreated or treated with conservative modalities Data Extraction and Synthesis Patient-level data were sought for studies reporting outcomes of treatment with fibrinolysis Summary statistics were obtained for conservative treatment and natural history studies The studies were weighted by the inverse of variance and merged in a random-effects model Main Outcomes and Measures Rate of visual recovery (defined as improvement of visual acuity from 20/200 or worse at presentation to 20/100 or better) was calculated for patients treated with fibrinolytic and conservative therapies and those who received no treatment Results We obtained summary statistics from 7 studies that included 396 patients who received no treatment after CRAO and from 8 studies that included 419 patients treated with ocular massage, anterior chamber paracentesis, and/or hemodilution (conservative treatment) Patient-level data were obtained for 147 patients treated with systemic fibrinolysis We found that fibrinolysis was beneficial at 45 hours or earlier after symptom onset compared with the natural history group (17 of 34 [500%] vs 70 of 396 [177%]; odds ratio, 47 [95% CI, 23-96]; P P Conclusions and Relevance Our analysis suggests that a clinical trial of early systemic fibrinolytic therapy for CRAO is warranted and that conservative treatments are futile and may be harmful

Carotid stenting and intracranial thrombectomy for treatment of acute stroke due to tandem occlusions with aggressive antiplatelet therapy may be associated with a high incidence of intracranial hemorrhage

Abstract: Background Acute stroke from tandem extracranial carotid artery and intracranial large vessel occlusion poses challenges for emergency endovascular treatment. Establishing and maintaining patency of the carotid artery and avoiding intracranial hemorrhage are competing concerns. Methods Twenty-three consecutive cases of emergency carotid stenting followed by mechanical thrombectomy identified by retrospective review of the endovascular ischemic stroke database maintained prospectively at our institution since January 2011 form the basis for this report. No cases were lost to follow-up. Results Patients were selected with CT angiography or MR angiography and diffusion weighted imaging. Carotid stenting was successful in all cases, and establishment of Thrombolysis in Cerebral Ischemia 2A, 2B or 3 flow was successful in 21/23 (91%). 12/23 (52%) patients achieved a modified Rankin Scale score of 0–2 at 90 days. Symptomatic intracranial hemorrhage (SICH) occurred in 5/23 patients (22%). Of 13 patients receiving an intravenous loading dose of abciximab during the procedure, 4/13 had SICH (31%) compared with 1/10 (10%) of those who did not. Of seven patients who received intravenous tissue plasminogen activator prior to the procedure, none had SICH. 90-day mortality was 9/23 (39%). All patients who had SICH were above the median age. Conclusions Primary stenting of the extracranial carotid artery combined with intracranial mechanical thrombectomy can be an effective treatment for tandem occlusions, can be performed with a high rate of technical success, and can achieve good clinical outcomes in selected patients. However, the incidence of SICH may be higher than in other patient populations and may be associated with the use of abciximab and advanced patient age.

Mechanical Thrombectomy in Cerebral Venous Thrombosis Systematic Review of 185 Cases

Abstract: Background and Purpose—Cerebral venous thrombosis is generally treated with anticoagulation. However, some patients do not respond to medical therapy and these might benefit from mechanical thrombectomy. The aim of this study was to gain a better understanding of the efficacy and safety of mechanical thrombectomy in patients with cerebral venous thrombosis, by performing a systematic review of the literature. Methods—We identified studies published between January 1995 and February 2014 from PubMed and Ovid. We included all cases of cerebral venous thrombosis in whom mechanical thrombectomy was performed with or without intrasinus thrombolysis. Good outcome was defined as normal or mild neurological deficits at discharge (modified Rankin Scale, 0–2). Secondary outcome variables included periprocedural complications and recanalization rates. Results—Our study included 42 studies (185 patients). Sixty percent of patient had a pretreatment intracerebral hemorrhage and 47% were stuporous or comatose. AngioJet...

Absolute and Relative Contraindications to IV rt-PA for Acute Ischemic Stroke.

Abstract: Most of the contraindications to the administration of intravenous (IV) recombinant tissue plasminogen activator (rtPA) originated as exclusion criteria in major stroke trials. These were derived from expert consensus for the National Institute of Neurological Disorders and Stroke (NINDS) trial. Despite the fact that the safety and efficacy of IV rtPA has been repeatedly confirmed in large international observational studies over the past 20 years, most patients with acute ischemic stroke disappointingly still do not receive thrombolytic treatment. Some of the original exclusion criteria have proven to be unnecessarily restrictive in real-world clinical practice. It has been suggested that application of relaxed exclusion criteria might increase the IV thrombolysis rate up to 20% with comparable outcomes to thrombolysis with more conventional criteria. We review the absolute and relative contraindications to IV rtPA for acute ischemic stroke, discussing the underlying rationale and evidence supporting these exclusion criteria.

Endovascular vs medical management of acute ischemic stroke

Abstract: Objective: To compare the outcomes between endovascular and medical management of acute ischemic stroke in recent randomized controlled trials (RCT). Methods: A systematic literature review was performed, and multicenter, prospective RCTs published from January 1, 2013, to May 1, 2015, directly comparing endovascular therapy to medical management for patients with acute ischemic stroke were included. Meta-analyses of modified Rankin Scale (mRS) and mortality at 90 days and symptomatic intracranial hemorrhage (sICH) for endovascular therapy and medical management were performed. Results: Eight multicenter, prospective RCTs (Interventional Management of Stroke [IMS] III, Local Versus Systemic Thrombolysis for Acute Ischemic Stroke [SYNTHESIS] Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy [MR RESCUE], Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands [MR CLEAN], Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE], Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial [EXTEND-IA], Solitaire With the Intention For Thrombectomy as Primary Endovascular Treatment [SWIFT PRIME], and Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours [REVASCAT]) comprising 2,423 patients were included. Meta-analysis of pooled data demonstrated functional independence (mRS 0–2) at 90 days in favor of endovascular therapy (odds ratio [OR] = 1.71; p = 0.005). Subgroup analysis of the 6 trials with large vessel occlusion (LVO) criteria also demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.23; p p Conclusions: This meta-analysis provides strong evidence that endovascular intervention combined with medical management, including IV tissue plasminogen activator for eligible patients, improves the outcomes of appropriately selected patients with acute ischemic stroke in the setting of LVO.

Effect of the use of ambulance-based thrombolysis on time to thrombolysis in acute ischemic stroke: a randomized clinical trial.

Abstract: UNLABELLED Article chosen Ebinger M, Winter B, Wendt M, et al. Effect of the use of ambulance-based thrombolysis on time to thrombolysis in acute ischemic stroke: a randomized clinical trial. JAMA 2014;311(16):1622-31. Clinical question Does prehospital thrombolysis in specialized ambulances reduce delay to thrombolysis in acute ischemic stroke? OBJECTIVE To determine the effect of prehospital thrombolysis for acute ischemic stroke administered in specialized ambulances on delay in thrombolytic administration, thrombolysis rate, post-thrombolysis intracerebral hemorrhage, and 7-day mortality.

Perfusion computed tomography to assist decision making for stroke thrombolysis

Abstract: The use of perfusion imaging to guide selection of patients for stroke thrombolysis remains controversial because of lack of supportive phase three clinical trial evidence. We aimed to measure the outcomes for patients treated with intravenous recombinant tissue plasminogen activator (rtPA) at a comprehensive stroke care facility where perfusion computed tomography was routinely used for thrombolysis eligibility decision assistance. Our overall hypothesis was that patients with 'target' mismatch on perfusion computed tomography would have improved outcomes with rtPA. This was a prospective cohort study of consecutive ischaemic stroke patients who fulfilled standard clinical/non-contrast computed tomography eligibility criteria for treatment with intravenous rtPA, but for whom perfusion computed tomography was used to guide the final treatment decision. The 'real-time' perfusion computed tomography assessments were qualitative; a large perfusion computed tomography ischaemic core, or lack of significant perfusion lesion-core mismatch were considered relative exclusion criteria for thrombolysis. Specific volumetric perfusion computed tomography criteria were not used for the treatment decision. The primary analysis compared 3-month modified Rankin Scale in treated versus untreated patients after 'off-line' (post-treatment) quantitative volumetric perfusion computed tomography eligibility assessment based on presence or absence of 'target' perfusion lesion-core mismatch (mismatch ratio >1.8 and volume >15 ml, core <70 ml). In a second analysis, we compared outcomes of the perfusion computed tomography-selected rtPA-treated patients to an Australian historical cohort of non-contrast computed tomography-selected rtPA-treated patients. Of 635 patients with acute ischaemic stroke eligible for rtPA by standard criteria, thrombolysis was given to 366 patients, with 269 excluded based on visual real-time perfusion computed tomography assessment. After off-line quantitative perfusion computed tomography classification: 253 treated patients and 83 untreated patients had 'target' mismatch, 56 treated and 31 untreated patients had a large ischaemic core, and 57 treated and 155 untreated patients had no target mismatch. In the primary analysis, only in the target mismatch subgroup did rtPA-treated patients have significantly better outcomes (odds ratio for 3-month, modified Rankin Scale 0-2 = 13.8, P < 0.001). With respect to the perfusion computed tomography selected rtPA-treated patients (n = 366) versus the clinical/non-contrast computed tomography selected rtPA-treated patients (n = 396), the perfusion computed tomography selected group had higher adjusted odds of excellent outcome (modified Rankin Scale 0-1 odds ratio 1.59, P = 0.009) and lower mortality (odds ratio 0.56, P = 0.021). Although based on observational data sets, our analyses provide support for the hypothesis that perfusion computed tomography improves the identification of patients likely to respond to thrombolysis, and also those in whom natural history may be difficult to modify with treatment.

Stroke Neurologist’s Perspective on the New Endovascular Trials

Abstract: Before December 2014, the only proven effective treatment for acute ischemic stroke was recombinant tissue-type plasminogen activator (r-tPA). This has now changed with the publication of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits--Intra-Arterial (EXTEND IA), Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment Trial (SWIFT PRIME), and Randomized Trial of Revascularization With the Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT) studies. We review the main results of these studies and how they inform stroke patient management going forward. The main take home points for neurologists are (1) intra-arterial thrombectomy is a potently effective treatment and should be offered to patients who have documented occlusion in the distal internal carotid or the proximal middle cerebral artery, have a relatively normal noncontrast head computed tomographic scan, severe neurological deficit, and can have intra-arterial thrombectomy within 6 hours of last seen normal; (2) benefits are clear in patients receiving r-tPA before intra-arterial thrombectomy; r-tPA should not be withheld if the patient meets criteria, and benefit in patients who do not receive r-tPA or have r-tPA exclusions requires further study; and (3) these favorable results occur when intra-arterial thrombectomy is performed in an endovascular stroke center by a coordinated multidisciplinary team that extends from the prehospital stage to the endovascular suite, minimizes time to recanalization, uses stent-retriever devices, and avoids general anesthesia. In conclusion, stroke teams, including practicing neurologists caring for patients with stroke should now provide the option for intra-arterial thrombectomy for a subset of patients with acute stroke.

Thrombus density predicts successful recanalization with Solitaire stent retriever thrombectomy in acute ischemic stroke

Abstract: Background Thrombus characteristics, including Hounsfield unit (HU) value to measure density and thrombus volume and length, can predict successful recanalization following IV thrombolysis with recombinant tissue plasminogen activator. Conflicting and limited data exist regarding the value of assessing thrombus properties in acute stroke cases treated with endovascular IA approaches. Methods We retrospectively reviewed cases of anterior circulation acute ischemic stroke in which a Solitaire stent retriever (ev3-Covidien) was the primary treatment device. We measured the following thrombus characteristics: absolute and corrected HU values; thrombus length and volume; clot burden score; and vessel bifurcation involvement. Fisher9s exact test and the t test were used to study the association between these clot characteristics and successful recanalization (Thrombolysis in Cerebral Infarction (TICI) score 2b–3). Results We identified 41 patients with anterior circulation stroke treated with the Solitaire stent retriever as the primary treatment device. Successful recanalization (TICI score 2b–3) was achieved in 59% of cases. Higher absolute and corrected HU values were strongly predictive of successful recanalization (49.9±7.6 vs 43.8±6.6, p=0.01 for absolute HU values and 1.2±0.2 vs 1.0±0.1, p=0.03 for HU ratio in TICI 2b–3 and TICI 0–2a groups, respectively). There was no significant difference between recanalization and non-recanalization groups in the other thrombus characteristics studied. Conclusions In acute stroke treated with Solitaire stent retriever thrombectomy, higher thrombus HU values are predictive of successful recanalization. Such information can be used in decision making when estimating recanalization success rate with different endovascular treatment approaches.

Endovascular Therapy for Ischemic Stroke

Abstract: To the Editor: In their report on the Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial (EXTEND-IA) trial, Campbell et al. (March 12 issue)(1) suggest that in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), local investigators might have selected patients on the basis of findings on computed tomographic (CT) perfusion imaging, although such selection was not specified in the protocol.(2),(3) We compared the effect of endovascular therapy in patients with and in those without CT perfusion data. In 166 patients without such data, the adjusted common odds . .

Ultrasound-Assisted Versus Conventional Catheter-Directed Thrombolysis for Acute Iliofemoral Deep Vein Thrombosis

Abstract: Background— For patients with acute iliofemoral deep vein thrombosis, it remains unclear whether the addition of intravascular high-frequency, low-power ultrasound energy facilitates the resolution of thrombosis during catheter-directed thrombolysis. Methods and Results— In a controlled clinical trial, 48 patients (mean age 50±21 years, 52% women) with acute iliofemoral deep vein thrombosis were randomized to receive ultrasound-assisted catheter-directed thrombolysis (N=24) or conventional catheter-directed thrombolysis (N=24). Thrombolysis regimen (20 mg r-tPA over 15 hours) was identical in all patients. The primary efficacy end point was the percentage of thrombus load reduction from baseline to 15 hours according to the length-adjusted thrombus score, obtained from standardized venograms and evaluated by a core laboratory blinded to group assignment. The percentage of thrombus load reduction was 55%±27% in the ultrasound-assisted catheter-directed thrombolysis group and 54%±27% in the conventional catheter-directed thrombolysis group ( P =0.91). Adjunctive angioplasty and stenting was performed in 19 (80%) patients and in 20 (83%) patients, respectively ( P >0.99). Treatment-related complications occurred in 3 (12%) and 2 (8%) patients, respectively ( P >0.99). At 3-month follow-up, primary venous patency was 100% in the ultrasound-assisted catheter-directed thrombolysis group and 96% in the conventional catheter-directed thrombolysis group ( P =0.33), and there was no difference in the severity of the post-thrombotic syndrome (mean Villalta score: 3.0±3.9 [range 0–15] versus 1.9±1.9 [range 0–7]; P =0.21), respectively. Conclusions— In this randomized controlled clinical trial of patients with acute iliofemoral deep vein thrombosis treated with a fixed-dose catheter thrombolysis regimen, the addition of intravascular ultrasound did not facilitate thrombus resolution. Clinical Trial Registration— URL: . Unique identifier: [NCT01482273][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01482273&atom=%2Fcirccvint%2F8%2F1%2Fe002027.atom

Outcomes in Mild Acute Ischemic Stroke Treated With Intravenous Thrombolysis A Retrospective Analysis of the Get With the Guidelines-Stroke Registry

Abstract: Importance Mild strokes have been poorly represented in thrombolytic trials and only a few series have reported outcomes after treatment with intravenous (IV) recombinant tissue plasminogen activator (rtPA) after mild stroke. Objective To report treatment complications and short-term outcomes in patients with mild stroke who have received treatment with IV rtPA. Design, Setting, and Participants Retrospective analysis of patients treated in the emergency department of hospitals that use the Get With the Guidelines–Stroke registry, a prospectively collected quality improvement registry used by hospitals across the United States. Patients were those admitted between May 1, 2010, and October 1, 2012, with acute ischemic stroke within 4.5 hours from symptom onset and a baseline National Institutes of Health Stroke Scale score of 5 or less. Univariable and multivariable analyses were performed to identify factors independently associated with discharge outcomes and treatment complications. Intervention Intravenous rtPA. Main Outcomes and Measures Treatment complications included symptomatic intracranial hemorrhage, life-threatening or serious systemic hemorrhage, other serious complications, and undetermined complications. The short-term outcomes analyzed were in-hospital mortality, discharge to home, independent ambulation at discharge, and length of stay. Results Among 33 995 patients who arrived within 4.5 hours of symptom onset and were treated with IV rtPA, 7621 (22.4%) had a National Institutes of Health Stroke Scale score of 5 or less and 5910 had complete data for analysis. Treatment complications were infrequent: symptomatic intracranial hemorrhage, 1.8%; life-threatening or serious systemic hemorrhage, 0.2%; other serious complications, 1.8%; and complications of undetermined cause, 2.4%. Mortality was low (1.3%), but at discharge 30.3% could not ambulate independently, 29.4% could not go directly home, and 73.0% had a length of stay of 3 days or longer. Worse short-term outcomes were seen in older patients, African American patients, diabetic patients, and those who arrived by ambulance, after hours, or with a higher National Institutes of Health Stroke Scale score. Conclusions and Relevance Many patients with ischemic stroke treated with IV rtPA have a mild stroke. Symptomatic intracranial hemorrhage is infrequent, but approximately 30% of these patients are unable to return directly home or ambulate independently at discharge. Additional studies are needed to identify strategies to improve the outcomes in patients with mild stroke who receive thrombolysis.

Uric Acid Therapy Improves Clinical Outcome in Women With Acute Ischemic Stroke

Abstract: Background and Purpose—It is unknown whether women and men with acute ischemic stroke respond similar to an antioxidant regimen administered in combination with thrombolysis. Here, we investigated the independent effect of sex on the response to uric acid (UA) therapy in patients with acute stroke treated with alteplase. Methods—In the Efficacy Study of Combined Treatment With Uric Acid and rtPA in Acute Ischemic Stroke (URICO-ICTUS) trial, 206 women and 205 men were randomized to UA 1000 mg or placebo. In this reanalysis of the trial, the primary outcome was the rate of excellent outcome at 90 days (modified Rankin Scale, 0–1, or 2, if premorbid score of 2) in women and men using regression models adjusted for confounders associated with sex. The interaction of UA levels by treatment on infarct growth was assessed in selected patients. Results—Excellent outcome occurred in 47 of 111 (42%) women treated with UA, and 28 of 95 (29%) treated with placebo, and in 36 of 100 (36%) men treated with UA and 38 of ...

Worse stroke outcome in atrial fibrillation is explained by more severe hypoperfusion, infarct growth, and hemorrhagic transformation

Abstract: BackgroundAtrial fibrillation is associated with greater baseline neurological impairment and worse outcomes following ischemic stroke. Previous studies suggest that greater volumes of more severe baseline hypoperfusion in patients with history of atrial fibrillation may explain this association. We further investigated this association by comparing patients with and without atrial fibrillation on initial examination following stroke using pooled multimodal magnetic resonance imaging and clinical data from the Echoplanar Imaging Thrombolytic Evaluation Trial and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies.MethodsEchoplanar Imaging Thrombolytic Evaluation Trial was a trial of 101 ischemic stroke patients randomized to intravenous tissue plasminogen activator or placebo, and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution was a prospective cohort of 74 ischemic stroke patients treated with intravenous tissue plasminogen activator at...

A systematic review and meta-analysis of randomized controlled trials of endovascular thrombectomy compared with best medical treatment for acute ischemic stroke

Abstract: BackgroundAcute ischemic strokes involving occlusion of large vessels usually recanalize poorly following treatment with intravenous thrombolysis. Recent studies have shown higher recanalization an...

Direct Imaging of Cerebral Thromboemboli Using Computed Tomography and Fibrin-targeted Gold Nanoparticles

Abstract: Computed tomography (CT) is the current standard for time-critical decision-making in stroke patients, informing decisions on thrombolytic therapy with tissue plasminogen activator (tPA), which has a narrow therapeutic index. We aimed to develop a CT-based method to directly visualize cerebrovascular thrombi and guide thrombolytic therapy. Glycol-chitosan-coated gold nanoparticles (GC-AuNPs) were synthesized and conjugated to fibrin-targeting peptides, forming fib-GC-AuNP. This targeted imaging agent and non-targeted control agent were characterized in vitro and in vivo in C57Bl/6 mice (n = 107) with FeCl3-induced carotid thrombosis and/or embolic ischemic stroke. Fibrin-binding capacity was superior with fib-GC-AuNPs compared to GC-AuNPs, with thrombi visualized as high density on microCT (mCT). mCT imaging using fib-GC-AuNP allowed the prompt detection and quantification of cerebral thrombi, and monitoring of tPA-mediated thrombolytic effect, which reflected histological stroke outcome. Furthermore, recurrent thrombosis could be diagnosed by mCT without further nanoparticle administration for up to 3 weeks. fib-GC-AuNP-based direct cerebral thrombus imaging greatly enhance the value and information obtainable by regular CT, has multiple uses in basic / translational vascular research, and will likely allow personalized thrombolytic therapy in clinic by a) optimizing tPA-dosing to match thrombus burden, b) enabling the rational triage of patients to more radical therapies such as endovascular clot-retrieval, and c) potentially serving as a theranostic platform for targeted delivery of concurrent thrombolysis.

Endovascular Therapy for Stroke — It's about Time

Abstract: Although many stroke centers worldwide have performed endovascular stroke therapy since the results of the Prolyse in Acute Cerebral Thromboembolism (PROACT) II trial were published in 1999,1 lingering uncertainties about efficacy and the selection of patients created an uneasy equipoise. Especially nettlesome was the uncertain benefit of endovascular therapy as compared with intravenous tissue plasminogen activator (t-PA). The controversy over endovascular therapy was heightened in 2013 when the results of the Interventional Management of Stroke (IMS) III,2 Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE),3 and Local versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS Expansion)4 clinical . . .