Intravenous Alteplase Research Articles

Safety and efficacy of intravenous thrombolysis in stroke patients on prior antiplatelet therapy in the WAKE-UP trial

BackgroundOne quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial.MethodsWAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0–1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase.ResultsOf 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years, p < 0.001), and more frequently had a history of hypertension, atrial fibrillation, diabetes, hypercholesterolemia, and previous stroke or transient ischaemic attack. Rates of symptomatic intracranial hemorrhage and hemorrhagic transformation on follow-up imaging did not differ between patients with and without antiplatelet treatment. Patients on prior antiplatelet treatment were less likely to achieve a favorable outcome (37.3% vs. 52.6%, p = 0.014), but there was no interaction of prior antiplatelet treatment with intravenous alteplase concerning favorable outcome (p = 0.355). Intravenous alteplase was associated with higher rates of favorable outcome in patients on prior antiplatelet treatment with an adjusted odds ratio of 2.106 (95% CI 1.047–4.236).ConclusionsTreatment benefit of intravenous alteplase and rates of post-treatment hemorrhagic transformation were not modified by prior antiplatelet intake among MRI-selected patients with unknown onset stroke. Worse functional outcome in patients on antiplatelets may result from a higher load of cardiovascular co-morbidities in these patients.

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. None.

Polypharmacy, functional outcome and treatment effect of intravenous alteplase for acute ischaemic stroke.

Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke. This was a post hoc analysis of the randomized, placebo-controlled WAKE-UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0-1 on the modified Rankin Scale at 90days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs. 64years; p<0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs. 5; p=0.0007). A comorbidity load defined by a CCI score≥2 was more frequent in patients with polypharmacy (48% vs. 8%; p<0.001). Polypharmacy was associated with lower odds of favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30-0.85; p=0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p=0.29). In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase.

Bridge mechanical thrombectomy may be a better choice for acute large vessel occlusions.

Direct mechanical thrombectomy (DMT) was confirmed non-inferior to bridge mechanical thrombectomy (BMT, MT preceded by intravenous alteplase within 4.5h after symptom onset) for acute ischemic stroke with large vessel occlusions (AIS-LVO) in mothership patients. However, the noninferiority of DMT in the general population (including drip and ship mode) is controversial, and the impact of thrombolysis on retrieval attempts remains uncertain. This was a post-hoc analysis of a multi-center, prospective enrolled study. Patients were divided into the BMT group and the DMT group. Baseline characteristics and clinical outcomes were compared by using univariate analysis, multivariable analysis, and propensity score matching analysis, respectively. Of all 245 patients enrolled in this study, 79 (32.2%) patients underwent BMT. In the multivariable analysis, the ratio of excellent prognosis (defined as modified Rankin Scale [mRS] score 0-1 at 90days) was significantly higher in the BMT group compared with the DMT group (odds ratio, 2.731; 95% confidence interval, 1.238-6.023; P = 0.013). The ratio of good prognosis (mRS score 0-2 at 90days), successful recanalization rate [modified Thrombolysis In Cerebral Ischemia (mTICI) score 2b-3] and mortality rate were similar between the two groups. The excellent prognosis rate was significantly higher in the BMT group after propensity score matching (P = 0.023). BMT was associated with a higher ratio of excellent prognosis (mRS 0-1) and a similar successful recanalization rate without increasing peri-operation complications compared with DMT in AIS-LVO patients. It is prudent to continue BMT until further data is available.

Clinical Course of Acute Ischemic Stroke Due to Medium Vessel Occlusion With and Without Intravenous Alteplase Treatment.

Available data on the clinical course of patients with acute ischemic stroke due to medium vessel occlusion (MeVO) are mostly limited to those with M2 segment occlusions. Outcomes are generally better compared with more proximal occlusions, but many patients will still suffer from severe morbidity. We aimed to determine the clinical course of acute ischemic stroke due to MeVO with and without intravenous alteplase treatment. Patients with MeVO (M2/M3/A2/A3/P2/P3 occlusion) from the INTERRSeCT (The Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) and PRoveIT (Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy) studies were included. Baseline characteristics and clinical outcomes were summarized using descriptive statistics. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days, describing excellent functional outcome. Secondary outcomes were the common odds ratio for a 1-point shift across the modified Rankin Scale and functional independence, defined as modified Rankin Scale score of 0 to 2. We compared outcomes between patients with versus without intravenous alteplase treatment and between patients who did and did not show recanalization on follow-up computed tomography angiography. Logistic regression was used to provide adjusted effect-size estimates. Among 258 patients with MeVO, the median baseline National Institutes of Health Stroke Scale score was 7 (interquartile range: 5-12). A total of 72.1% (186/258) patients were treated with intravenous alteplase and in 41.8% (84/201), recanalization of the occlusion (revised arterial occlusive lesion score 2b/3) was seen on follow-up computed tomography angiography. Excellent functional outcome was achieved by 50.0% (129/258), and 67.4% (174/258) patients gained functional independence, while 8.9% (23/258) patients died within 90 days. Recanalization was observed in 21.4% (9/42) patients who were not treated with alteplase and 47.2% (75/159) patients treated with alteplase (P=0.003). Early recanalization (adjusted odds ratio, 2.29 [95% CI, 1.23-4.28]) was significantly associated with excellent functional outcome, while intravenous alteplase was not (adjusted odds ratio, 1.70 [95% CI, 0.88-3.25]). One of every 2 patients with MeVO did not achieve excellent clinical outcome at 90 days with best medical management. Early recanalization was strongly associated with excellent outcome but occurred in <50% of patients despite intravenous alteplase treatment.

Combined utility of blood glucose and white blood cell in predicting outcome after acute ischemic stroke: The ENCHANTED trial

BackgroundAs hyperglycemia and leukocytosis individually predict poor outcome in acute ischemic stroke (AIS), we aimed to determine the significance of their combination on functional outcome and symptomatic intracerebral hemorrhage (sICH) among participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). MethodsPost-hoc analyzes of the full ENCHANTED cohort, an international, multicenter, quasi-factorial, randomized, open, blinded outcome-assessed trial of low- versus standard-dose intravenous alteplase and early intensive versus standard blood pressure (BaP) lowering treatment in 4557 thrombolysis-eligible and treated AIS patients. Patients were divided into four groups according to baseline blood glucose and white blood cells (WBC) levels: A (normal glucose + WBC), B (hyperglycemia + normal WBC), C (normal glucose + high WBC), and D (hyperglycemia + high WBC). Logistic regression models were used to determine associations of each group and poor functional outcome (modified Rankin scale scores 2−6) at 90 days and sICH within 48 h, adjusted for confounders. Quality of model fit was examined with Akaike information classification (AIC), Bayesian information classification (BIC), and likelihood ratio test. ResultsOf 4181 AIS patients included in analyzes, and with group A as the reference, an increasing odds of poor functional outcome was evident across groups B (odds ratio [OR] 1.38, 95 % confidence interval [CI] 1.17−1.63), C (OR 1.26, 95 %CI 0.99−1.60), and D (OR 2.26, 95 %CI 1.79−2.85) (P trend <0.001). Group D patients also had a higher rate of sICH (P trend <0.05). The model fit with the combination of blood glucose and WBC was better than models of their individual components. ConclusionsUsing a combination of blood glucose and WBC provides strong prognostic significance than either alone in thrombolyzed AIS patients.

In ischemic stroke, thrombectomy alone was noninferior to thrombectomy plus alteplase for functional outcome at 90 days.

Yang P, Zhang Y, Zhang L, et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. N Engl J Med. 2020;382:1981-93. 32374959.

Thrombolysis as first-line therapy for Medtronic/HeartWare HVAD left ventricular assist device thrombosis.

We reviewed our institutional experience with intravenous thrombolysis (TL) as first-line therapy in patients with Medtronic/HeartWare HVAD left ventricular assist device pump thrombosis (PT). From March 2006 to November 2018, 30 Medtronic/HeartWare HVAD left ventricular assist device patients had 48 PT events. We analysed outcomes with intravenous Alteplase as a first-line therapy for PT. Pump exchange or urgent heart transplantation was only considered after the failure of TL or existing contraindications to TL. TL was used as the first-line therapy in 44 PT events in 28 patients without a contraindication to TL. TL was successful in 61.4% of PT events. More than 1 cycle of TL was necessary in 55.6% of events. The combined success of TL and heart transplantation or device exchange was 81.8%. In 15.9% of events, PT was fatal. Causes of death were severe complications (9.1%) related to TL or discontinuation of therapy for multi-organ failure (6.8%). Intracranial bleeding and arterial thromboembolism were observed in 4.5% and 11.5% of the PT events after TL. Intravenous TL as a first-line therapy for PT in Medtronic/HeartWare HVAD patients can be a reasonable treatment option and does not preclude subsequent heart transplantation or device exchange. However, thromboembolic and bleeding complications are common. The decision to perform TL or device exchange should, therefore, be made on an individual basis after balancing the risks and benefits of different treatment approaches.

Clinical Characteristics and Outcome of Patients With Hemorrhagic Transformation After Intravenous Thrombolysis in the WAKE-UP Trial.

Background: Hemorrhagic transformation (HT) is an important complication of intravenous thrombolysis with alteplase. HT can show a wide range from petechiae to parenchymal hematoma with mass effect with varying clinical impact. We studied clinical and imaging characteristics of patients with HT and evaluated whether different types of HT are associated with functional outcome.Methods: We performed a post-hoc analysis of WAKE-UP, a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in unknown onset stroke. HT was assessed on follow-up MRI or CT and diagnosed as hemorrhagic infarction type 1 and type 2 (HI1 and HI2, combined as HI), and parenchymal hemorrhage type 1 and type 2 (PH1 and PH2, combined as PH). Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS) at baseline. Stroke lesion volume was measured on baseline diffusion weighted imaging (DWI). Primary endpoint was a favorable outcome defined as a modified Rankin Scale score 0–1 at 90 days.Results: Of 483 patients included in the analysis, 95 (19.7%) showed HI and 21 (4.4%) had PH. Multiple logistic regression analysis identified treatment with alteplase (OR, 2.08 [95% CI, 1.28–3.40]), baseline NIHSS score (OR, 1.11 [95% CI, 1.05–1.17]), DWI lesion volume (OR, 1.03 [95% CI, 1.01–1.05]), baseline glucose levels (OR, 1.01 [95% CI, 1.00–1.01]) and atrial fibrillation (OR, 3.02 [95% CI, 1.57–5.80]) as predictors of any HT. The same parameters predicted HI. Predictors of PH were baseline NIHSS score (OR, 1.11 [95% CI, 1.01–1.22]) and as a trend treatment with alteplase (OR, 2.40 [95% CI, 0.93–6.96]). PH was associated with lower odds of favorable outcome (OR 0.25, 95% [CI 0.05–0.86]), while HI was not.Conclusion: Our results indicate that HI is associated with stroke severity, cardiovascular risk factors and thrombolysis. PH is a rare complication, more frequent in severe stroke and with thrombolysis. In contrast to HI, PH is associated with worse functional outcome. The impact of HT after MRI-guided intravenous alteplase for unknown onset stroke on clinical outcome is similar as in the trials of stroke thrombolysis within a known early time-window.

Study of alteplase for respiratory failure in severe acute respiratory syndrome coronavirus 2/COVID‐19: Study design of the phase IIa STARS trial

BackgroundThe coronavirus disease 2019 (COVID‐19) pandemic has caused a large surge of acute respiratory distress syndrome (ARDS). Prior phase I trials (non–COVID‐19) demonstrated improvement in pulmonary function in patients ARDS using fibrinolytic therapy. A follow‐up trial using the widely available tissue‐type plasminogen activator (t‐PA) alteplase is now needed to assess optimal dosing and safety in this critically ill patient population. ObjectiveTo describe the design and rationale of a phase IIa trial to evaluate the safety and efficacy of alteplase treatment for moderate/severe COVID‐19–induced ARDS. Patients/MethodsA rapidly adaptive, pragmatic, open‐label, randomized, controlled, phase IIa clinical trial will be conducted with 3 groups: intravenous alteplase 50 mg, intravenous alteplase 100 mg, and control (standard‐of‐care). Inclusion criteria are known/suspected COVID‐19 infection with PaO2/FiO2 ratio <150 mm Hg for > 4 hours despite maximal mechanical ventilation management. Alteplase will be delivered through an initial bolus of 50 mg or 100 mg followed by heparin infusion for systemic anticoagulation, with alteplase redosing if there is a >20% PaO2/FiO2 improvement not sustained by 24 hours. ResultsThe primary outcome is improvement in PaO2/FiO2 at 48 hours after randomization. Other outcomes include ventilator‐ and intensive care unit–free days, successful extubation (no reintubation ≤3 days after initial extubation), and mortality. Fifty eligible patients will be enrolled in a rapidly adaptive, modified stepped‐wedge design with 4 looks at the data. ConclusionFindings will provide timely information on the safety, efficacy, and optimal dosing of t‐PA to treat moderate/severe COVID‐19–induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).

August 2020 Highlights.

August 2020 Highlights.

Brain Imaging Signs and Health-Related Quality of Life after Acute Ischemic Stroke: Analysis of ENCHANTED Alteplase Dose Arm

Background and Purpose: The influence of specific brain lesions on health-related quality of life (HRQoL) after acute ischemic stroke (AIS) is uncertain. We aimed to identify imaging predictors of poor HRQoL in alteplase-treated participants of the alteplase dose arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: ENCHANTED was an international trial of low- versus standard-dose intravenous alteplase in AIS patients, with functional outcome (modified Rankin scale [mRS]) and HRQoL on the 5-dimension European Quality of Life Scale (EQ-5D) assessed at 90 days post-randomization. Brain images were analyzed centrally by trained assessors. Multivariable logistic regression was undertaken in the study population randomly divided (2:1) into training (development) and validation (performance) groups, with age (per 10-year increase), ethnicity, baseline National Institutes of Health Stroke Scale (NIHSS) score, diabetes mellitus, premorbid function (mRS score 0 or 1), and proxy respondent, forced into all models. Data are presented with odds ratios (ORs) and 95% confidence intervals (CIs). Results: Eight prediction models were developed and validated in 2,526 AIS patients (median age 67.5 years; 38.4% female; 61.7% Asian) with complete brain imaging and 90-day EQ-5D utility score data. The best performance model included acute ischemic changes in the right (OR 1.69, 95% CI: 1.24–2.29) and deep (OR 1.50, 95% CI: 1.03–2.19) middle cerebral artery (MCA) regions. Several background features of brain frailty – atrophy, white matter change, and old infarcts – were significantly associated with adverse physical but not emotional HRQoL domains. Conclusions: In thrombolysed AIS patients, right-sided and deep ischemia within the MCA territory predict poor overall HRQoL, whilst features of old cerebral ischemia are associated with reduced physical HRQoL.

Endovascular Therapy or Alteplase in Patients with Comorbidities: Insights from UNMASK EVT.

Decisions to treat large-vessel occlusion with endovascular therapy (EVT) or intravenous alteplase depend on how physicians weigh benefits against risks when considering patients' comorbidities. We explored EVT/alteplase decision-making by stroke experts in the setting of comorbidity/disability. In an international multi-disciplinary survey, experts chose treatment approaches under current resources and under assumed ideal conditions for 10 of 22 randomly assigned case scenarios. Five included comorbidities (cancer, cardiac/respiratory/renal disease, mild cognitive impairment [MCI], physical dependence). We examined scenario/respondent characteristics associated with EVT/alteplase decisions using multivariable logistic regressions. Among 607 physicians (38 countries), EVT was chosen less often in comorbidity-related scenarios (79.6% under current resources, 82.7% assuming ideal conditions) versus six "level-1A" scenarios for which EVT/alteplase was clearly indicated by current guidelines (91.1% and 95.1%, respectively, odds ratio [OR] [current resources]: 0.38, 95% confidence interval 0.31-0.47). However, EVT was chosen more often in comorbidity-related scenarios compared to all other 17 scenarios (79.6% versus 74.4% under current resources, OR: 1.34, 1.17-1.54). Responses favoring alteplase for comorbidity-related scenarios (e.g. 75.0% under current resources) were comparable to level-1A scenarios (72.2%) and higher than all others (60.4%). No comorbidity independently diminished EVT odds when considering all scenarios. MCI and dependence carried higher alteplase odds; cancer and cardiac/respiratory/renal disease had lower odds. Being older/female carried lower EVT odds. Relevant respondent characteristics included performing more EVT cases/year (higher EVT-, lower alteplase odds), practicing in East Asia (higher EVT odds), and in interventional neuroradiology (lower alteplase odds vs neurology). Moderate-to-severe comorbidities did not consistently deter experts from EVT, suggesting equipoise about withholding EVT based on comorbidities. However, alteplase was often foregone when respondents chose EVT. Differences in decision-making by patient age/sex merit further study.

Efficacy and Safety of Intravenous Thrombolysis on Acute Branch Atheromatous Disease: A Retrospective Case-Control Study.

Background and Objective: Branch atheromatous disease (BAD) is distinctive from large-artery atherosclerosis and small-vessel disease, which is single subcortical infarction caused by the occlusion of perforator's orifice. This study aimed to indicate whether intravenous thrombolysis (IVT) with alteplase could prevent early neurological deterioration (END) and improve functional outcome for patients with BAD within 4.5 h after symptom onset.Methods: We retrospectively analyzed data collected from patients with BAD who were admitted to our hospital from January 2015 to August 2019. To investigate the efficacy and safety of IVT, subjects were classified into alteplase and control groups. A propensity score matching analysis was performed to control substantial heterogeneity of subgroup. The coprimary outcomes were END that is defined as an increase of ≥2 points in the National Institutes of Health Stroke Scale (NIHSS) score within 7 days after stroke, and favorable outcome at 3 months after stroke that defined by a score of 0–1 point on the modified Rankin scale (mRS).Results: A total of 135 patients were eventually enrolled in this study (n = 51 for the alteplase group and n = 84 for the control group). Additionally, 42 pairs of subjects were successfully matched by propensity score matching. Intravenous alteplase within 4.5 h after stroke onset reduced the incidence of END [unadjusted odds ratio (OR), 3.32; 95% confidence interval (CI), 1.06–10.37] and improved the clinical outcome at 3 months after stroke, with more patients achieving favorable functional prognosis (mRS, 0–1 point; unadjusted OR, 0.25; 95% CI, 0.10–0.62). Patients in the alteplase group were more likely to be independent (mRS, 0–2 points) at 3 months after stroke (unadjusted OR, 0.33; 95% CI, 0.12–0.90). The rate of death or dependence (mRS, ≥4 points) in the alteplase group was also markedly lower than that in the control group (unadjusted OR, 4.06; 95% CI, 1.03–16.02).Conclusion: Our findings indicated that intravenous thrombolysis may be a safe and effective therapy for patients with BAD.

Management of Acute Ischemic Stroke-Specific Focus on Anesthetic Management for Mechanical Thrombectomy.

Acute ischemic stroke is a neurological emergency with a high likelihood of morbidity, mortality, and long-term disability. Modern stroke care involves multidisciplinary management by neurologists, radiologists, neurosurgeons, and anesthesiologists. Current American Heart Association/American Stroke Association (AHA/ASA) guidelines recommend thrombolytic therapy with intravenous (IV) alteplase within the first 3-4.5 hours of initial stroke symptoms and endovascular mechanical thrombectomy within the first 16-24 hours depending on specific inclusion criteria. The anesthesia and critical care provider may become involved for airway management due to worsening neurologic status or to enable computerized tomography (CT) or magnetic resonance imaging (MRI) scanning, to facilitate mechanical thrombectomy, or to manage critical care of stroke patients. Existing data are unclear whether the mechanical thrombectomy procedure is best performed under general anesthesia or sedation. Retrospective cohort trials favor sedation over general anesthesia, but recent randomized controlled trials (RCT) neither suggest superiority nor inferiority of sedation over general anesthesia. Regardless of anesthesia type, a critical element of intraprocedural stroke care is tight blood pressure management. At different phases of stroke care, different blood pressure targets are recommended. This narrative review will focus on the anesthesia and critical care providers' roles in the management of both perioperative stroke and acute ischemic stroke with a focus on anesthetic management for mechanical thrombectomy.

Highlights of Selected Articles July 2020.

Highlights of Selected Articles July 2020.

Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis.

Central retinal artery occlusion results in sudden, painless, usually permanent loss of vision in the affected eye. There is no proven, effective treatment to salvage visual acuity and a clear, unmet need for an effective therapy. In this work, we evaluated the efficacy of intravenous tissue-type plasminogen activator (IV alteplase) in a prospective cohort study and an updated systematic review and meta-analysis. We enrolled consecutive patients with acute central retinal artery occlusion within 48 hours of symptoms onset and with a visual acuity of <20/200 from January 2009 until May 2019. The primary outcomes were safety and functional visual acuity recovery. We compared rates of visual recovery between those treated with alteplase within 4.5 hours of symptom onset to those who did not receive alteplase (including an analysis restricted to untreated patients presenting within the window for treatment). We incorporated these results into an updated systematic review and patient-level meta-analysis. We enrolled 112 patients, of whom 25 (22.3% of the cohort) were treated with IV alteplase. One patient had an asymptomatic intracerebral hemorrhage after IV alteplase treatment. Forty-four percent of alteplase-treated patients had recovery of visual acuity when treated within 4.5 hours versus 13.1% of those not treated with alteplase (P=0.003) and 11.6% of those presenting within 4 hours who did not receive alteplase (P=0.03). Our updated patient-level meta-analysis of 238 patients included 67 patients treated with alteplase within 4.5 hours since time last known well with a recovery rate of 37.3%. This favorably compares with a 17.7% recovery rate in those without treatment. In linear regression, earlier treatment correlated with a higher rate of visual recovery (P=0.01). This study showed that the administration of intravenous alteplase within 4.5 hours of symptom onset is associated with a higher likelihood of a favorable visual outcome for acute central retinal artery occlusion. Our results strongly support proceeding to a randomized, placebo-controlled clinical trial.

Telestroke in the Time of COVID-19: The Mayo Clinic Experience

On March 11, 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) a pandemic, and in the weeks following, public health organizations, medical associations, and governing bodies throughout the world recommended limiting contact with others to “flatten the curve” of COVID-19. Although both ischemic and hemorrhagic strokes have been reported with COVID-19, there has been anecdotal suggestion of an overall decrease in stroke admissions. To date, the effects of any pandemic on telestroke service lines have not been described. The purpose of this cross-sectional analysis of telestroke activations in the 30 days before and after the declaration of the COVID-19 pandemic is to describe the difference in case volumes of telestroke activations, the characteristics of patients, and treatment recommendations between the 2 time frames. We found a 50.0% reduction in total telestroke activations between the predeclaration group (142 patients) and the postdeclaration group (71 patients). There were no statistically significant differences in age (P=.95), sex (P=.10), diagnosis (P=.26), or regional variations (P=.08) in activation volumes. The percentage of patients for whom we recommended urgent stroke treatment with intravenous alteplase, mechanical thrombectomy, or both decreased from 44.4% (28 of 63) to 33.3% (11 of 33). The reasons for the sunstantial decrease in telestroke activations and urgent stroke treatment recommendations are likely multifactorial but nevertheless underscore the importance of continued public health measures to encourage patients and families to seek emergency medical care at the time of symptom onset.

Thrombectomy for Stroke in the Public Health Care System of Brazil

BackgroundRandomized trials involving patients with stroke have established that outcomes are improved with the use of thrombectomy for large-vessel occlusion. These trials were performed in high-resource countries and have had limited effects on medical practice in low- and middle-income countries.MethodsWe studied the safety and efficacy of thrombectomy in the public health system of Brazil. In 12 public hospitals, patients with a proximal intracranial occlusion in the anterior circulation that could be treated within 8 hours after the onset of stroke symptoms were randomly assigned in a 1:1 ratio to receive standard care plus mechanical thrombectomy (thrombectomy group) or standard care alone (control group). The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days.ResultsA total of 300 patients were enrolled, including 79 who had undergone thrombectomy during an open-label roll-in period. Approximately 70% in the two groups received intravenous alteplase. The trial was stopped early because of efficacy when 221 of a planned 690 patients had undergone randomization (111 to the thrombectomy group and 110 to the control group). The common odds ratio for a better distribution of scores on the modified Rankin scale at 90 days was 2.28 (95% confidence interval [CI], 1.41 to 3.69; P=0.001), favoring thrombectomy. The percentage of patients with a score on the modified Rankin scale of 0 to 2, signifying an absence of or minor neurologic deficit, was 35.1% in the thrombectomy group and 20.0% in the control group (difference, 15.1 percentage points; 95% CI, 2.6 to 27.6). Asymptomatic intracranial hemorrhage occurred in 51.4% of the patients in the thrombectomy group and 24.5% of those in the control group; symptomatic intracranial hemorrhage occurred in 4.5% of the patients in each group.ConclusionsIn this randomized trial conducted in the public health care system of Brazil, endovascular treatment within 8 hours after the onset of stroke symptoms in conjunction with standard care resulted in better functional outcomes at 90 days than standard care alone. (Funded by the Brazilian Ministry of Health; RESILIENT ClinicalTrials.gov number, NCT02216643.)

Are EMS bypass policies effective implementation strategies for intravenous alteplase for stroke?

BackgroundStroke is a leading cause of disability and the fifth leading cause of death in the USA. Intravenous alteplase is a highly effective clot-dissolving stroke treatment that must be given in a hospital setting within a time-sensitive window. To increase the use of intravenous alteplase in stroke patients, many US counties enacted policies mandating emergency medical service (EMS) paramedics to bypass local emergency departments and instead directly transport patients to specially equipped stroke centers. The objective of this mixed-methods study is to evaluate the effectiveness of policy enactment as an implementation strategy, how differences in policy structures and processes impact effectiveness, and to explore how the county, hospital, and policy factors explain variation in implementation and clinical outcomes. This paper provides a detailed description of an Agency for Healthcare Quality and Research (AHRQ)-funded protocol, including the use of the Consolidated Framework for Implementation Research (CFIR) in the qualitative design.Methods/designWe will construct the largest-ever national stroke database of Medicare enrollees (~ 1.5 million stroke patients) representing 896 policy counties paired with 1792 non-policy counties, then integrate patient-, hospital-, county-, and state-level covariates from eight different data sources. We will use a difference-in-differences analysis to estimate the overall effect of the policy enactment on intravenous alteplase use (implementation outcome) as well as key patient outcomes. We will also quantitatively examine if variation in the context (urban/rural status) and variation in policy features affect outcomes. Finally, a CFIR-informed multiple case study design will be used to interview informants in 72 stakeholders in 24 counties to identify and validate factors that enable policy effects.DiscussionPolicies can be potent implementation strategies. However, the effects of EMS bypass policies to increase intravenous alteplase use have not been rigorously evaluated. By learning how context and policy structures impact alteplase implementation, as well as the barriers and facilitators experienced by stakeholders responsible for policy enactment, the results of this study will inform decisions regarding if and how EMS bypass policies should spread to non-policy counties, and if indicated, creation of a “best practices” toolkit.