Intravenous Thrombolysis For Acute Stroke Research Articles

Optimizing Patient-Centered Stroke Care and Research in the Prehospital Setting.

Over the past decades, continuous technological advances and the availability of novel therapies have enabled treatment of more acute medical conditions than ever before. Many of these treatments, such as intravenous thrombolysis and mechanical thrombectomy for acute ischemic stroke, are highly time sensitive. This has raised interest in shifting advanced acute care from hospitals to the prehospital setting. Key objectives of advanced prehospital stroke care may include (1) early targeted treatments in the prehospital setting, for example, intravenous thrombolysis for acute stroke, and (2) advanced prehospital diagnostics such as prehospital large vessel occlusion and intracranial hemorrhage detection, to help inform patient triage and potentially reduce subsequent workload in emergency departments. Major challenges that may hamper a swift transition to more advanced prehospital care are related to conducting clinical trials in the prehospital setting to provide sufficient evidence for emergency interventions, as well as ambulance design, infrastructure, emergency medical service personnel training and workload, and cost barriers. Utilizing new technologies such as telemedicine, mobile stroke units and portable diagnostic devices, customized software applications, and smart storage space management may help surmount these challenges and establish efficient, targeted care strategies that are achievable in the prehospital setting. In this article, we delineate the paradigm of shifting advanced stroke care to the prehospital setting and outline future directions in providing evidence-based, patient-centered prehospital care. While we use acute stroke as an illustrative example, these principles are not limited to stroke patients and can be applied to prehospital triage for any time-critical disease.

Using simulation and machine learning to maximise the benefit of intravenous thrombolysis in acute stroke in England and Wales: the SAMueL modelling and qualitative study

BackgroundStroke is a common cause of adult disability. Expert opinion is that about 20% of patients should receive thrombolysis to break up a clot causing the stroke. Currently, 11–12% of patients in England and Wales receive this treatment, ranging between 2% and 24% between hospitals.ObjectivesWe sought to enhance the national stroke audit by providing further analysis of the key sources of inter-hospital variation to determine how a target of 20% of stroke patients receiving thrombolysis may be reached.DesignWe modelled three aspects of the thrombolysis pathway, using machine learning and clinical pathway simulation. In addition, the project had a qualitative research arm, with the objective of understanding clinicians’ attitudes to use of modelling and machine learning applied to the national stroke audit.Participants and data sourceAnonymised data were collected for 246,676 emergency stroke admissions to acute stroke teams in England and Wales between 2016 and 2018, obtained from the Sentinel Stroke National Audit Programme.ResultsUse of thrombolysis could be predicted with 85% accuracy for those patients with a chance of receiving thrombolysis (i.e. those arriving within 4 hours of stroke onset). Machine learning models allowed prediction of likely treatment choice for each patient at all hospitals. A clinical pathway simulation predicted hospital thrombolysis use with an average absolute error of 0.5 percentage points. We found that about half of the inter-hospital variation in thrombolysis use came from differences in local patient populations, and half from in-hospital processes and decision-making. Three changes were applied to all hospitals in the model: (1) arrival to treatment in 30 minutes, (2) proportion of patients with determined stroke onset times set to at least the national upper quartile and (3) thrombolysis decisions made based on majority vote of a benchmark set of 30 hospitals. Any single change alone was predicted to increase national thrombolysis use from 11.6% to between 12.3% and 14.5% (with clinical decision-making having the most effect). Combined, these changes would be expected to increase thrombolysis to 18.3% (and to double the clinical benefit of thrombolysis, as speed increases also improve clinical benefit independently of the proportion of patients receiving thrombolysis); however, there would still be significant variation between hospitals depending on local patient population. For each hospital, the effect of each change could be predicted alone or in combination. Qualitative research with 19 clinicians showed that engagement with, and trust in, the model was greatest in physicians from units with higher thrombolysis rates. Physicians also wanted to see a machine learning model predicting outcome with probability of adverse effect of thrombolysis to counter a fear that driving thrombolysis use up may cause more harm than good.LimitationsModels may be built using data available in the Sentinel Stroke National Audit Programme only. Not all factors affecting use of thrombolysis are contained in Sentinel Stroke National Audit Programme data and the model, therefore, provides information on patterns of thrombolysis use in hospitals, but is not suitable for, or intended as, a decision aid to thrombolysis.ConclusionsMachine learning and clinical pathway simulation may be applied at scale to national audit data, allowing extended use and analysis of audit data. Stroke thrombolysis rates of at least 18% look achievable in England and Wales, but each hospital should have its own target.Future workFuture studies should extend machine learning modelling to predict the patient-level outcome and probability of adverse effects of thrombolysis, and apply co-production techniques, with clinicians and other stakeholders, to communicate model outputs.FundingThis project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full inHealth and Social Care Delivery Research; Vol. 10, No. 31. See the NIHR Journals Library website for further project information.

Use of Clinical Pathway Simulation and Machine Learning to Identify Key Levers for Maximizing the Benefit of Intravenous Thrombolysis in Acute Stroke.

Background:Expert opinion is that about 20% of emergency stroke patients should receive thrombolysis. Currently, 11% to 12% of patients in England and Wales receive thrombolysis, ranging from 2% to 24% between hospitals. The aim of this study was to assess how much variation is due to differences in local patient populations, and how much is due to differences in clinical decision-making and stroke pathway performance, while estimating a realistic target thrombolysis use.Methods:Anonymised data for 246 676 emergency stroke admissions to 132 acute hospitals in England and Wales between 2016 and 2018 was obtained from the Sentinel Stroke National Audit Programme data. We used machine learning to learn decisions on who to give thrombolysis to at each hospital. We used clinical pathway simulation to model effects of changing pathway performance. Qualitative research was used to assess clinician attitudes to these methods. Three changes were modeled: (1) arrival-to-treatment in 30 minutes, (2) proportion of patients with determined stroke onset times set to at least the national upper quartile, (3) thrombolysis decisions made based on majority vote of a benchmark set of hospitals.Results:Of the modeled changes, any single change was predicted to increase national thrombolysis use from 11.6% to between 12.3% to 14.5% (clinical decision-making having the most effect). Combined, these changes would be expected to increase thrombolysis to 18.3%, but there would still be significant variation between hospitals depending on local patient population. Clinicians engaged well with the modeling, but those from hospitals with lower thrombolysis use were most cautious about the methods.Conclusions:Machine learning and clinical pathway simulation may be applied at scale to national stroke audit data, allowing extended use and analysis of audit data. Stroke thrombolysis rates of at least 18% look achievable in England and Wales, but each hospital should have its own target.

Tenecteplase for acute ischaemic stroke

The introduction of intravenous thrombolysis for acute ischaemic stroke has changed the outlook of stroke neurology, altering the field from a rehabilitation focus to emergency medicine. Because the treatment effect of intravenous thrombolysis in acute stroke is time dependent, stroke services globally are constantly striving to reduce the time from symptom onset to treatment by promoting stroke awareness campaigns, implementing prehospital delivery of thrombolysis in mobile stroke units, and restructuring in-hospital protocols to reduce door-to-needle time.

Author Response: Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial.

We are grateful for the interest in our article on the treatment effect of alteplase in acute ischemic stroke patients with preexisting cerebral microbleeds (CMBs).1 The readers point out that new lesions are observed on susceptibility-weighted imaging (SWI) in patients with artificial heart valves that meet the imaging criteria of CMBs and suggest that these lesions should be differentiated from CMBs associated with small vessel disease to better identify patients with an increased bleeding risk.2 Of interest, a previous study showed that new CMBs occurring in acute ischemic stroke patients after receiving IV thrombolysis (IVT) were indeed associated with an increased risk of IVT-related hemorrhagic complications.3 On the other hand, new CMBs were not associated with an increased risk of bleeding in patients undergoing cardiac surgery.2,4 However, IVT may constitute a different bleeding risk than cardiopulmonary bypass and extracorporeal membrane oxygenation, or a prolonged intensive care unit stay. The question of whether CMBs in patients with artificial heart valves represent a different pathophysiologic entity with a different bleeding risk merits further research and would profit from histopathology studies and observational studies in stroke and nonstroke cohorts with long-term follow-up.

Editors' Note: Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial

Dr. Schlemm et al. performed a prespecified analysis of the association of cerebral microbleeds (CMBs) with the treatment effect of IV alteplase vs placebo in the randomized controlled WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke) trial of patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch on MRI. Among 459 patients available for analysis, there was no evidence of reduced treatment effect of alteplase in the 98 (21.4%) patients who had at least 1 CMB on baseline imaging. However, CMBs were associated with a nonsignificant increased risk of symptomatic intracranial hemorrhage (ICH; 11.2% vs 4.2%; adjusted odds ratio 2.32, 95% CI 0.99–5.43). In response, Drs. Meinel and Seiffge highlight the importance of distinguishing patients with CMBs from cerebral amyloid angiopathy or other cerebral small vessel disease—who have an increased risk of postthrombolysis ICH—from those with other causes of CMBs and other such lesions on susceptibility-weighted imaging, like those seen after valve implantation, extracorporeal membrane oxygenation, or prolonged intensive care unit stay. They also recommend examining the interaction of CMBs and white matter hyperintensities to better elucidate the risk of postthrombolysis hemorrhage. Responding to these comments, the authors note that new CMBs in acute ischemic stroke patients after IV thrombolysis were associated with an increased risk of hemorrhagic complications in prior literature, whereas new CMBs after cardiac surgery were not associated with bleeding risk, suggesting different risk profiles for patients with different causes of acute CMBs—a topic meriting further investigation in histopathology and observational studies. This exchange highlights the challenges of disentangling cause-specific bleeding risks associated with CMBs when examining ICH outcomes in patients undergoing thrombolysis. Dr. Schlemm et al. performed a prespecified analysis of the association of cerebral microbleeds (CMBs) with the treatment effect of IV alteplase vs placebo in the randomized controlled WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke) trial of patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch on MRI. Among 459 patients available for analysis, there was no evidence of reduced treatment effect of alteplase in the 98 (21.4%) patients who had at least 1 CMB on baseline imaging. However, CMBs were associated with a nonsignificant increased risk of symptomatic intracranial hemorrhage (ICH; 11.2% vs 4.2%; adjusted odds ratio 2.32, 95% CI 0.99–5.43). In response, Drs. Meinel and Seiffge highlight the importance of distinguishing patients with CMBs from cerebral amyloid angiopathy or other cerebral small vessel disease—who have an increased risk of postthrombolysis ICH—from those with other causes of CMBs and other such lesions on susceptibility-weighted imaging, like those seen after valve implantation, extracorporeal membrane oxygenation, or prolonged intensive care unit stay. They also recommend examining the interaction of CMBs and white matter hyperintensities to better elucidate the risk of postthrombolysis hemorrhage. Responding to these comments, the authors note that new CMBs in acute ischemic stroke patients after IV thrombolysis were associated with an increased risk of hemorrhagic complications in prior literature, whereas new CMBs after cardiac surgery were not associated with bleeding risk, suggesting different risk profiles for patients with different causes of acute CMBs—a topic meriting further investigation in histopathology and observational studies. This exchange highlights the challenges of disentangling cause-specific bleeding risks associated with CMBs when examining ICH outcomes in patients undergoing thrombolysis.

Reader Response: Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial.

Reader Response: Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial.

Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial.

Background and ObjectivesCerebral microbleeds (CMBs) are common in patients with acute ischemic stroke and are associated with increased risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis. Whether CMBs modify the treatment effect of thrombolysis is unknown.MethodsWe performed a prespecified analysis of the prospective randomized controlled multicenter Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial including patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch on MRI receiving alteplase or placebo. Patients were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). Patients were randomized to treatment with IV thrombolysis with alteplase at 0.9 mg/kg body weight or placebo. CMB status (presence, number, and distribution) was assessed after study completion by 3 raters blinded to clinical information following a standardized protocol. Outcome measures were excellent functional outcome at 90 days, defined by modified Rankin Scale (mRS) score ≤1, and symptomatic ICH according to National Institutes of Neurological Disease and Stroke trial criteria 22 to 36 hours after treatment.ResultsOf 503 patients enrolled in the WAKE-UP trial, 459 (91.3%; 288 [63%] men) were available for analysis. Ninety-eight (21.4%) had at least 1 CMB on baseline imaging; 45 (9.8%) had exactly 1 CMB; 37 (8.1%) had 2 to 4 CMBs; and 16 (3.5%) had ≥5 CMBs. Presence of CMBs was associated with a nonsignificant increased risk of symptomatic ICH (11.2% vs 4.2%; adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 0.99–5.43, p = 0.052) but had no effect on functional outcome at 90 days (mRS score ≤1: 45.8% vs 50.7%; adjusted OR 0.99, 95% CI 0.59–1.64, p = 0.955). Patients receiving alteplase had better functional outcome (mRS score ≤1: 54.6% vs 44.6%, adjusted OR 1.61, 95% CI 1.07–2.43, p = 0.022) without evidence of heterogeneity in relation to CMB presence (p of the interactive term = 0.546). Results were similar for subpopulations with strictly lobar (presumed cerebral amyloid angiopathy related) or not strictly lobar CMB distribution.DiscussionIn the randomized-controlled WAKE-UP trial, we saw no evidence of reduced treatment effect of alteplase in patients with acute ischemic stroke with ≥1 CMBs. Additional studies are needed to determine the treatment effect of alteplase and its benefit-harm ratio in patients with a larger number of CMBs.Trial Registration InformationClinicalTrials.gov identifier NCT01525290; ClinicalTrialsRegister.EU identifier 2011-005906-32.Classification of EvidenceThis study provides Class II evidence that for patients with acute ischemic stroke with unknown time of onset and diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch who received IV alteplase, CMBs are not significantly associated with functional outcome at 90 days.

MSC 2021 Virtual E-Abstract

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Endovascular therapy with or without intravenous thrombolysis in acute stroke with tandem occlusion

BackgroundEndovascular therapy (EVT) is effective and safe in patients with tandem occlusion. The benefit of intravenous thrombolysis (IVT) prior to EVT in acute tandem occlusion is debatable.ObjectiveTo compare EVT alone...

Can Carotid Endarterectomy be Performed Safely within 14 days after Intravenous Thrombolysis for Acute Stroke?

Carotid endarterectomy (CEA) represents a standard procedure in case of symptomatic carotid stenosis of 50-99% within 2weeks from onset of stroke or transient ischemic attack (TIA) symptoms. The optimal time to perform CEA after intravenous thrombolysis (IVT) is still unclear. The aim of this study was to analyze the safety of CEA performed within 2weeks from IVT. A consecutive series of 70 patients affected by symptomatic carotid stenosis have been treated as per the international guidelines during 3years. Eleven (15.7%) patients have been treated with IVT before CEA for ischemic stroke; remaining 59 (84.3%) patients received only CEA. CEA was performed in median 8days (range: 2-13) after IVT. We examined the grade of disability before and after surgery as well as at 3months follow-up, using the modified Ranking Scale (mRS). Among the patients who underwent CEA+IVT, CEA was performed in median 8days (range: 2-13) after IVT. One patient received CEA within 48hours from IVT, 3 patients within 72hours, and 7 patients within 2weeks. The complications within 90days from surgery, in CEA+IVT group, were 3 cases of intracerebral hemorrhage (ICH) without symptoms. In patients who received only CEA, the complications were 1 case of stroke and 2 cases of ICH. The mortality registered was 0% in both groups. Among CEA+IVT group at 90days after surgery, 9 patients had a mRS grade of 0-2, 2 patients had mRS of 3-5. In our series, IVT before CEA did not seem to increase the rate of complications. However, the study has several limitations, and further studies must be performed before solid evidence is available for recommendations regarding the timing of CEA after IVT.

Safety of Intravenous Thrombolysis for Acute Stroke in Patients with an Active Malignancy: Case Series and Review of the Literature

Introduction: Evidence is scarce regarding the safety of alteplase for acute stroke in patients with an active malignancy. Methods: We reviewed medical records for patients with both conditions treated at our institution over a 2-year period. Results: Five patients were identified, of which only one developed an asymptomatic intracerebral haemorrhage, and no systemic bleedings occurred. Functional outcomes and stroke severity, as measured by National Institutes of Health Stroke Scale and modified Rankin Scale, were favourable upon discharge. Conclusion: In the absence of active bleeding or known malignancy of the central nervous system, intravenous alteplase seems a reasonable option for patients with an active cancer and acute stroke.

Relationships between brain perfusion and early recanalization after intravenous thrombolysis for acute stroke with large vessel occlusion

In large vessel occlusion (LVO) stroke, it is unclear whether severity of ischemia is involved in early post-thrombolysis recanalization over and above thrombus site and length. Here we assessed the relationships between perfusion parameters and early recanalization following intravenous thrombolysis administration in LVO patients. From a multicenter registry, we identified 218 thrombolysed LVO patients referred for thrombectomy with both (i) pre-thrombolysis MRI, including diffusion-weighted imaging (DWI), T2*-imaging, MR-angiography and dynamic susceptibility-contrast perfusion-weighted imaging (PWI); and (ii) evaluation of recanalization on first angiographic run or non-invasive imaging ≤ 3 h from thrombolysis start. Infarct core volume on DWI, PWI-DWI mismatch volume and hypoperfusion intensity ratio (HIR; defined as Tmax ≥ 10 s volume/ Tmax ≥ 6 s volume, low HIR indicating milder hypoperfusion) were determined using a commercially available software. Early recanalization occurred in 34 (16%) patients, and multivariable analysis was associated with lower HIR (P = 0.006), shorter thrombus on T2*-imaging (P < 0.001) and more distal occlusion (P = 0.006). However, the relationship between HIR and early recanalization was robust only for thrombus length <14 mm. In summary, the present study disclosed an association between lower HIR and early post-thrombolysis recanalization. Early post-thrombolysis recanalization is therefore determined not only by thrombus site and length but also by severity of ischemia.

Abstract WP65: Relationships Between Brain Perfusion and Early Recanalization After Intravenous Thrombolysis for Acute Stroke With Large Vessel Occlusion

Introduction: In large vessel occlusion (LVO) stroke, it is unclear whether severity of ischemia is involved in early post-intravenous thrombolysis (IVT) recanalization over and above thrombus site and length. Here we assessed the relationships between perfusion parameters and early recanalization following IVT administration in LVO patients. Methods: From a multicentre registry, 218 thrombolysed LVO patients referred for thrombectomy since May 2015 with both i) pre-IVT MRI, including diffusion-weighted imaging (DWI), T2* imaging, MR-angiography and dynamic susceptibility-contrast perfusion-weighted imaging (PWI); and ii) recanalization evaluated on first angiographic run or non-invasive imaging ≤3hrs from IVT start, were identified. Infarct core volume on DWI, PWI-DWI mismatch volume and Hypoperfusion Intensity Ratio (HIR; defined as the proportion of Tmax&gt;6s volume with Tmax&gt;10sec), a validated index of hypoperfusion severity, were determined using commercially available software. Results: Early recanalization occurred in 34 (16%) patients, and was independently associated with lower HIR ( P =0.006), shorter thrombus on T2* imaging ( P &lt;0.001) and more distal occlusion ( P= 0.006). DWI lesion volume and PWI-DWI mismatch volume both had significant univariable association with recanalization but were not retained in the multivariable model. In addition, there was a significant interaction between thrombus length and HIR such that the effect of lower HIR on recanalization was stronger for smaller thrombi. Conclusion: This study disclosed a novel, independent association between milder hypoperfusion severity, as assessed by the HIR, and early post-IVT recanalization. Perfusion imaging may help to identify LVO patients most likely to benefit from IVT before thrombectomy.

Thrombus Volume as a Predictor of Nonrecanalization After Intravenous Thrombolysis in Acute Stroke.

Background and Purpose- We investigated whether measuring the volume and density of a thrombus could predict nonrecanalization after intravenous thrombolysis. Methods- This study included a retrospective cohort to develop a computed tomography marker of thrombus for predicting nonrecanalization after intravenous thrombolysis and a prospective multicenter cohort for validation of this marker. The volume and density of thrombus were measured semiautomatically using 3-dimensional software on a baseline thin-section noncontrast computed tomography (1 or 1.25 mm). Recanalization was assessed on computed tomography angiography or magnetic resonance angiography immediately after intravenous thrombolysis or conventional angiography in patients who underwent further intra-arterial treatment. Nonrecanalization was defined as a modified Thrombolysis in Cerebral Infarction grade 0, 1, 2a. Results- In the retrospective cohort, 162 of 214 patients (76.7%) failed to achieve recanalization. The thrombus volume was significantly larger in patients with nonrecanalization than in those with successful recanalization (149.5±127.6 versus 65.3±58.3 mm3; P<0.001). In the multivariate analysis, thrombus volume was independently associated with nonrecanalization ( P<0.001). The cutoff for predicting nonrecanalization was calculated as 200 mm3. In the prospective multicenter validation study, none of the patients with a thrombus volume ≥200 mm3 among 78 enrolled patients achieved successful recanalization. The positive and negative predictive values were 95.5 and 29.4 in the retrospective cohort 100 and 23.3 in the prospective validation cohort, respectively. The thrombus density was not associated with nonrecanalization. Conclusions- Thrombus volume was predictive of nonrecanalization after intravenous thrombolysis. Measurement of thrombus volume may help in determining the recanalization strategy and perhaps identify patients suitable for direct endovascular thrombectomy.

Critical Event Intervals in Determining Candidacy for Intravenous Thrombolysis in Acute Stroke.

BackgroundThe aim of the study was to determine the optimal set point for the critical event benchmarks described in stroke guidelines and validate the ability of these goals to predict successful administration of intravenous thrombolysis within 60 min of hospital arrival.MethodsThis was a retrospective cohort analysis of patients with acute ischemic stroke who received intravenous thrombolysis following presentation to the emergency department. The national benchmarks for time intervals associated with the completion of critical events required to determine candidacy for thrombolysis were evaluated for the ability to predict successful administration of thrombolysis within 60 min of hospital arrival. Optimal time interval cut points were then estimated using regression and receiver-operator characteristic curve analysis and compared to guidelines.ResultsOf the 523 patients included in the analysis, 229 (43.8%) received intravenous thrombolysis within 60 min of hospital arrival. Of the patients who met the critical event interval goals described in guidelines, only 51.6% received thrombolysis within 60 min. The optimized cut points suggested by the regression analysis aligned with the guideline benchmarks with the only substantial difference being a shortened goal of arrival to neuroimaging start time of 19 min. This difference did not impact the overall predictive value.ConclusionThe critical event benchmarks proposed in this study by logistic regression closely correlate with the critical event benchmarks described in the AHA/ASA acute stroke guidelines.

Successful Intravenous Thrombolysis for Acute Stroke Caused by Polycythemia Vera

Successful Intravenous Thrombolysis for Acute Stroke Caused by Polycythemia Vera

Renal Dysfunction Is an Independent Risk Factor for Poor Outcome in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis: A New Cutoff Value.

Objective. This study was set to assess the effect of renal dysfunction on outcome of stroke patients treated with intravenous thrombolysis (IVT). Methods. This multicenter research involved 403 patients from January 2009 to March 2015. Patients were divided into two groups: (1) control group with GFR ≥ 45 mL/min/1.73 m2 and (2) low GFR group with GFR < 45 mL/min/1.73 m2. Outcome measurements were poor outcome (mRS 3–6) and mortality at 3 months and symptomatic intracerebral hemorrhage (SICH) within the first 24–36 hours. Univariate and multivariate regression analyses were performed, and odds ratios (ORs) were determined at 95% confidence intervals (CIs). Results. Univariate analyses determined that every decrease of GFR by 10 mL/min/1.73 m2 significantly increased the risk of poor outcome (OR 1.19, 95% CI 1.09–1.30, p < 0.001) and mortality (OR 1.18, 95% CI 1.06–1.32, p = 0.002). In multivariate regression, adjusted for all variables with p value < 0.1, low GFR (GFR < 45 versus GFR equal to or more than 45) was associated with poor outcome (OR adjusted 2.15, 95% CI 1.01–4.56, p = 0.045). Conclusion. In IVT for acute stroke, renal dysfunction with GFR < 45 mL/min/1.73 m2 before treatment determined increased odds for poor outcome compared to GFR of more than 45 mL/min/1.73 m2.

No space left for intravenous thrombolysis in acute stroke: PROS.

Five recently published RCTs (MR CLEAN, EXTEND-IA, SWIFT PRIME, REVASCAT and ESCAPE) employing mechanical thrombectomy with modern stent retriever devices clearly demonstrated the superiority of endovascular treatment compared to thrombolysis alone, which is now considered standard first-line therapy for selected patients with acute severe ischemic stroke and large vessel in the anterior circulation. RCT results led to recommendations outlined in "Mechanical thrombectomy in acute ischemic stroke by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN". Moreover, endovascular procedures in the 5 RCTs to date were performed at high-volume referral centers with, in some trials, rigid requirements for the interventionalist to participate, which may have contributed substantially to the excellent results, supporting the concept of centralization of intra-arterial thrombolysis resources and expertise. Therefore, patients with suspected large-artery occlusion and deemed candidates for thrombectomy, should be treated at a Comprehensive Stroke Centre with 24/7 endovascular treatment services. There seems to be limited space left for intravenous thrombolysis alone in acute stroke patients with large-vessel occlusions as thrombectomy plus thrombolysis continues to be reported as being superior with regard to outcome.

No space left for intravenous thrombolysis in acute stroke: CONS.

Recent successful clinical trials of endovascular thrombectomy for large artery ischaemic stroke have established the value of this treatment modality as an adjunct to intravenous thrombolysis, not as an alternative: thrombectomy delivery was undertaken in the context of highly efficient networks for acute thrombolysis delivery and the great majority of patients received IV thrombolytic drug treatment. Even for the minority of acute stroke patients for whom thrombectomy is potentially relevant, access will be limited by geography and service infrastructure. Developments in intravenous thrombolysis in the near future will likely produce safer and more effective intravenous treatments. Intravenous thrombolysis will remain the first line of treatment for the great majority of acute stroke patients.