IV Thrombolysis Research Articles

Risk of Aneurysm Rupture After Thrombolysis in Patients With Acute Ischemic Stroke and Unruptured Intracranial Aneurysms.

Unruptured intracranial aneurysms (UIAs) are considered to be a relative contraindication for IV thrombolysis (IVT) in acute ischemic stroke (AIS). Currently, however, data are limited on the risk of UIA rupture after IVT. Our objective was to assess whether IVT for AIS can lead to a UIA rupture and intracranial hemorrhages (ICHs) in patients with unruptured UIAs. This was a prospective cohort study of consecutive patients treated in a comprehensive stroke center between 2005 and 2019. We assessed radiology reports and records at the Finnish Care Register for Health Care to identify patients with UIAs among all patients with AIS treated with IVT at the center. We analyzed patient angiograms for aneurysm characteristics and other brain imaging studies for ICHs after IVT. The main outcome was in-hospital ICHs attributable to a UIA rupture after IVT. Secondary outcomes were in-hospital symptomatic ICHs (European-Australian Cooperative Acute Stroke Study [ECASS-2] criteria, i.e., NIH Stroke Scale score increase ≥4 points) and any in-hospital ICHs. A total of 3,953 patients were treated with IVT during the 15-year study period. One hundred thirty-two (3.3%) of the 3,953 patients with AIS had a total of 155 UIAs (141 saccular and 14 fusiform). The mean diameter of UIAs was 4.7 ± 3.8 mm, with 18.7% being ≥7 mm and 9.7% ≥10 mm in diameter. None of the 141 saccular UIAs ruptured after IVT. Three patients (2.3%, 95% confidence interval [CI] 0.6%-5.8%) with large fusiform basilar artery UIAs had a fatal rupture at 27 hours, 43 hours, and 19 days after IVT. All 3 were administered anticoagulation treatments after IVT, and anticoagulation took effect during the UIA rupture. Any ICHs and symptomatic ICHs were detected in 18.9% (95% CI 12.9%-26.2%) and 8.3% (95% CI 4.4%-13.8%) of all patients with AIS, respectively. IVT appears to be safe in patients with AIS with saccular UIAs, including larges UIAs (≥10 mm). Anticoagulation after AIS in patients with large fusiform posterior circulation UIAs may increase the risk of aneurysm rupture.

The Maryland Acute Stroke Emergency Medical Services Routing Pilot: Expediting Access to Thrombectomy for Stroke.

Background: Mechanical thrombectomy (MT) is the standard of care for acute ischemic stroke caused by large vessel occlusion, but is not available at all stroke centers. Transfers between hospitals lead to treatment delays. Transport directly to a facility capable of MT based on a prehospital stroke severity scale score has been recommended, if transportation time is less than 30 min.Aims: We hypothesized that an Emergency Medical Services (EMS) routing algorithm for stroke, using the Los Angeles Motor Scale (LAMS) in the field, would improve time from last known well to MT, without causing patients to miss the IV Thrombolysis (IVT) window.Methods: An EMS algorithm in the Baltimore metro area using the LAMS was implemented. Patients suspected of having an acute stroke were assessed by EMS using the LAMS. Patients scoring 4 or higher and within 20 h from last known well, were transported directly to a Thrombectomy Center, if transport could be completed within 30 min. The algorithm was evaluated retrospectively with prospectively collected data at the Thrombectomy Centers. The primary outcome variables were proportion of patients with suspected stroke rerouted by EMS, proportion of rerouted ischemic stroke patients receiving MT, time to treatment, and whether the IVT window was missed.Results: A total of 303 patients were rerouted out of 2459 suspected stroke patients over a period of 6 months. Of diverted patients, 47% had acute ischemic stroke. Of these, 48% received an acute stroke treatment: 16.8% IVT, 17.5% MT, and 14% MT+IVT. Thrombectomy occurred 119 min earlier in diverted patients compared to patients transferred from other hospitals (P = 0.006). 55.3% of diverted patients undergoing MT and 38.2% of patients transferred from hospital to hospital were independent at 90 days (modified Rankin score 0–2) (P = 0.148). No patient missed the time window for IVT due to the extra travel time.Conclusions: In this retrospective analysis of prospectively acquired data, implementation of a pre-hospital clinical screening score to detect patients with suspected acute ischemic stroke due to large vessel occlusion was feasible. Rerouting patients directly to a Thrombectomy Center, based on the EMS algorithm, led to a shorter time to thrombectomy.

Early Neurologic Deterioration in Lacunar Stroke: Clinical and Imaging Predictors and Association With Long-term Outcome.

To determine the rate and predictors of early neurologic deterioration (END) in patients with lacunar strokes and its implications for management and outcome. We enrolled consecutive patients with MRI-defined lacunar stroke who presented within 12 hours after symptom onset from a prospective stroke database (2015-2019). END was defined as any persisting increase in NIH Stroke Scale (NIHSS) score of ≥2 points within 24 hours after admission and favorable outcome as modified Rankin Scale (mRS) score of 0 to 2 at 90 days. We assessed the association of END with clinical and imaging variables, acute treatment, and outcome using multivariable regression, calculating adjusted odds ratios (aORs). Sixty-one of 365 (16.7%) patients with acute lacunar stroke (median age 71.8 years, 39.5% female, median NIHSS score on admission 3) had END. Lower NIHSS score on admission (per point, aOR 0.81, p = 0.006), capsular warning syndrome (aOR 7.00, p < 0.001), ventral pontine infarct (aOR 3.49, p = 0.008), and hypoperfusion lesion on imaging (aOR 2.13, p = 0.026) were associated with END. Acute dual antiplatelet therapy was associated with reduced risk of END (aOR 0.10, p = 0.04). Patients with END had less favorable outcome at 90 days (aOR 0.13 p < 0.001), but IV thrombolysis (IVT) was associated with favorable outcome at 90 days (aOR 3.95, p = 0.002). One in 6 patients with lacunar stroke has END, and patients at high risk of END can be identified with radiologic and clinical variables. Targeted therapeutic trials for this population seem justified. This study provides Class II evidence that early neurologic deterioration in patients with acute lacunar stroke predicts poorer functional outcome at 90 days as determined by the mRS.

Safety and Outcomes of Thrombectomy in Ischemic Stroke With vs Without IV Thrombolysis.

To test the hypothesis that IV thrombolysis (IVT) treatment before endovascular thrombectomy (EVT) is associated with better outcomes in patients with anterior circulation large artery occlusion (LAO) stroke, we examined a large real-world database, the Safe Implementation of Treatment in Stroke-International Stroke Thrombectomy Register (SITS-ISTR). We identified centers recording ≥10 consecutive patients in the SITS-ISTR, with at least 70% available modified Rankin Scale (mRS) scores at 3 months during 2014 to 2019. We defined LAO as intracranial internal carotid artery, first and second segment of middle cerebral artery, and first segment of anterior cerebral artery. Main outcomes were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial hemorrhage (SICH) per modified SITS-Monitoring Study. We performed propensity score-matched (PSM) and multivariable logistic regression analyses. Of 6,350 patients from 42 centers, 3,944 (62.1%) received IVT. IVT + EVT-treated patients had less frequent atrial fibrillation, ongoing anticoagulation, previous stroke, heart failure, and prestroke disability. PSM analysis showed that IVT + EVT-treated patients had a higher rate of functional independence than patients treated with EVT alone (46.4% vs 40.3%, p < 0.001) and a lower rate of death at 3 months (20.3% vs 23.3%, p = 0.035). SICH rates (3.5% vs 3.0%, p = 0.42) were similar in both groups. Multivariate adjustment yielded results consistent with PSM. Pretreatment with IVT was associated with favorable outcomes in EVT-treated LAO stroke in the SITS-ISTR. These findings, while indicative of international routine clinical practice, are limited by observational design, unmeasured confounding, and possible residual confounding by indication. This study provides Class II evidence that IVT before EVT increases the probability of functional independence at 3 months compared to EVT alone.

Safety and efficacy of antiplatelet use before intravenous thrombolysis for acute Ischemic stroke

AimTo study the effects of pretreatment with Antiplatelet (AP) before IV thrombolysis (IVT) on the rate of symptomatic intracranial hemorrhage (sICH) and functional outcome in patients with Acute Ischemic stroke (AIS). MethodIn this retrospective study, the medical records and cerebrovascular images of all the patients who received IVT for AIS in our center in a 9.6-year period were reviewed. Patients who took at least one dose of any APs in the last 24 h prior to IVT were identified. They were categorized according to the type of AP, single versus dual AP therapy (DAPT), and dose of AP. Rate of sICH and functional outcome at discharge were compared between the AP users and non-users. ResultsA total of 834 patients received IVT for AIS in our center during a 9.6- year period. Multivariate models were adjusted for age, NIHSS on admission, history of atrial fibrillation, history of hypertension, INR on admission, history of stroke and diabetes mellitus. In multivariate regression analyses and after adjusting for the variables mentioned above, the use of any AP was not associated with an increased rate of sICH (OR = 1.28 [0.70–2.34], p = 0.425). Furthermore, the use of DAPT did not significantly increase the rate of sICH in multivariate regression analyses. (OR = 0.663 [0.15–2.84], p = 0.580). The patients on any AP had a lower chance of having good functional outcome in univariate analysis (OR = 0.735 [0.552–0.979], p = 0.035). However, when adjusted for age, baseline NIHSS, history of diabetes, hypertension and prior stroke, AP use was not associated with a decreased chance of having a good functional outcome at discharge. (OR = 0.967 [0.690–1.357], p = 0.848). In addition, no significant difference was noted in the rate of good functional outcome between patients on DAPT and no AP users in multivariate regression analyses. (OR = 1.174 [0.612–2.253], p = 0.629). ConclusionOur study did not show any significant association between the risk of sICH and good functional outcome after IVT for AIS patients on AP therapy (dual or single) in comparison with AP naïve patients.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

Abstract P223: Effect of Collateral Status and Level of Reperfusion Achieved From Mechanical Thrombectomy on Rehabilitation Outcomes

Background: Good collateral flow has been shown to have better outcomes after acute ischemic stroke (AIS), including for patients receiving IV thrombolysis (IVT) and mechanical thrombectomy (MT). Hypothesis: In patients with AIS who undergo MT, good collateral flow is associated with better functional independence measure (FIM) change. Design/Methods: Data was collected retrospectively for patients who presented with AIS and were treated with MT. A total of 54 patients from 4 inpatient rehabilitation facility (IRF) locations between April 2017 and August 2019 were included. Collateral score was collected from angiograms and CT angiogram (CTA) in cases where an angiogram was not available. FIM change was defined as the difference in FIM at admission to IRF and discharge from IRF. Regression analyses were conducted to estimate the relationship between collateral score and FIM change. The predictors in the model included collateral score, FIM at admission to IRF, age at onset, and gender. Logistic regression was used for categorical variables and linear regression was applied for continuous variables. Statistical significance level was set at 0.05. Collaterals were scored from 0 to 4, with 0 to 2 being poor and good collateral flow defined as scores 3 and 4. The primary outcome of this study was FIM change. Results: The mean age was 70.4 years, and 54.5% was female. Regression analyses did not show any significant differences in FIM change in patients with collaterals ranging from poor to good p = 0.807 (Table 1), when adjusted for age, gender, and severity as represented by FIM at admission to IRF. Conclusion: In this patient cohort, good collateral flow was not associated with improvement in FIM change.

Abstract P17: Outcomes After Thrombolysis for Ischemic Stroke in Costa Rica Compare Favorably With International Cohorts

Background: More than 70% of strokes occur in resource-poor countries. Outcomes are often not well documented. rt-PA for acute ischemic stroke was approved in 2012 for use in Costa Rica (CR). A hub and spoke model was initiated and a dataset established, the CR Stroke Registry Program (CRSRP) for conditional- and post-approval monitoring. Here, we compared CRSRP rt-PA outcomes to similarly treated subjects from the 1995 NINDS rt-PA trial and the 2019 CLOTBUST-ER control arm. Methods: Subjects were matched using a published pairing methodology and day 7-10/discharge modified Rankin Score (mRS), symptomatic intracerebral hemorrhages (SICH) and early mortality compared. A mortality model was generated from 15 randomized controlled trials (RCTs) and outcomes compared at similar baselines. SICH rates were compared with other cohorts: Get With The Guidelines (GWTG), a combined international IV thrombolysis trial pool, and 2 Ibero-American populations. Results: Of 424 CRSRP patients, 284 receiving rt-PA under 3 hrs were matched with 308 NINDS subjects. 131 non-diabetic CRSRP subjects, treated within 4.5 hrs, NIHSS 10 - 24 and Alberta Stroke Program Early CT Score (ASPECTS)&gt;7, were matched with 300 CLOTBUST-ER subjects. Percent achieving either mRS 0-1 or 0-2 did not differ between CRSRP and either NINDS or CLOTBUST-ER (mRS 0-1: CRSRP:33.9% vs NINDS:33.6%; CRSRP:23.8% vs CLOTBUST-ER:27.0%, all p&gt;=.05 / mRS 0-2: CRSRP:40.0% vs NINDS:41.4%; CRSRP:31.1% vs CLOTBUST-ER:36.1%, all p=&gt;.05). Mortality was higher for CRSRP vs CLOTBUST-ER (6.6% vs 0.8%; p=0.05) but not vs NINDS (6.8% vs 4.3%; p=0.3). A predictive model (R 2 =0.39) showed neither cohort exceeded expected pooled mortality, with CLOTBUST-ER the lowest mortality. SICH rate was higher in CRSRP vs CLOTBUST-ER (7.3% vs 0.0% p=0.008) but not vs NINDS (5.7% vs 6.8% p=0.7)). SICH rates were not higher when compared with 4 international cohorts. Conclusion: Functional outcomes of Costa Rican patients receiving rt-PA compared favorably with 2 RCTs (NINDS and CLOTBUST-ER). SICH and mortality were higher than CLOTBUST-ER, although both were within expected range compared to other international cohorts. Systems of care development in order to further lower SICH and participate in the endovascular era are underway.

Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke.

To determine the effect of remote ischemic postconditioning (RIPC) on patients with acute ischemic stroke (AIS) undergoing IV thrombolysis (IVT). A single-center randomized controlled trial was performed with patients with AIS receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization. The primary endpoint was a score of 0 or 1 on the modified Rankin scale (mRS) at day 90. The safety, tolerability, and neuroprotection biomarkers associated with RIPC were also evaluated. We collected data from both the RIPC group (n = 34) and the control group (n = 34). The average duration of hospitalization was 11.2 days. There was no significant difference between 2 groups at admission for the NIH Stroke Scale score (p = 0.364) or occur-to-treatment time (p = 0.889). Favorable recovery (mRS score 0-1) at 3 months was obtained in 71.9% of patients in the RIPC group vs 50.0% in the control group (adjusted odds ratio 9.85, 95% confidence interval 1.54-63.16; p = 0.016). We further found significantly lower plasma S100-β (p = 0.007) and higher vascular endothelial growth factor (p = 0.003) levels in the RIPC group than in the control group. Repeated RIPC combined with IVT can significantly facilitate recovery of nerve function and improve clinical prognosis of patients with AIS. NCT03218293. This study provides Class IV evidence that RIPC after tissue plasminogen activator treatment of AIS significantly increases the proportion of patients with an MRS score of 0 or 1 at 90 days.

Statins Use and Outcome of Acute Ischemic Stroke Patients after Systemic Thrombolysis

Aim: The aim of this was to study the effects of statins and their intensity on symptomatic intracranial hemorrhage (sICH) and outcome after IV thrombolysis (IVT) for acute ischemic stroke (AIS). Methods: We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with IVT for AIS in our center in a 10-year period. Patients were further characterized as any statin users versus non-users on admission to the emergency department. Statins were categorized in high intensity or low intensity statin based on its propensity to reduce lower low-density cholesterol by ≥45% or <45%, respectively. Safety and discharge modified Rankin Score were compared between statin users versus non-users and also between high-intensity versus low-intensity groups. Results: A total of 834 patients received IVT for AIS in our center during a 10-year period. Multivariate models were adjusted for age, NIH Stroke Scale at admission, INR, and history of DM and atrial fibrillation. There was no association between odds of sICH and any statin use (OR = 0.52 [0.26–1.03], p = 0.06). In multivariate model, any statin use was not associated with odds of poor outcome (Table 4: OR = 1.01 [0.79–1.55], p = 0.57). There was no significant association between odds of sICH among patients on high-intensity statin compared to low intensity statin (multivariate model OR = 0.39 [0.11–1.40], p = 0.15). There was 47% reduced odds of poor outcome among patients on high-intensity statin as compared to low-intensity statin (OR = 0.53[0.32–0.88] p = 0.01). However, this significant association was lost in the multivariate model (OR = 0.60 [0.35–1.05], p = 0.07). Conclusion: Our study does not show any significant association between risk of sICH and poor outcome after IVT for patients on prior statin therapy. We also did not find significant association between the risk of sICH and poor outcome after IVT and the intensity of the stain used.

Association of prestroke metformin use, stroke severity, and thrombolysis outcome.

To evaluate whether pretreatment with metformin (MET) is associated with less stroke severity and better outcome after IV thrombolysis (IVT), we analyzed a cohort of 1,919 patients with stroke with type 2 diabetes mellitus in a multicenter exploratory analysis. Data from patients with diabetes and ischemic stroke treated with IVT were collected within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration. We applied propensity score matching (PSM) to obtain balanced baseline characteristics of patients treated with and without MET. Of 1,919 patients with stroke with type 2 diabetes who underwent IVT, 757 (39%) had received MET before stroke (MET+), whereas 1,162 (61%) had not (MET-). MET+ patients were younger with a male preponderance. Hypercholesterolemia and pretreatment with statins, antiplatelets, or antihypertensives were more common in the MET+ group. After PSM, the 2 groups were well balanced with respect to demographic and clinical aspects. Stroke severity on admission (NIH Stroke Scale 10.0 ± 6.7 vs 11.3 ± 6.5), 3-month degree of independence on modified Rankin Scale (2 [interquartile range (IQR) 1.0-4.0] vs 3 [IQR 1.0-4.0]), as well as mortality (12.5% vs 18%) were significantly lower in the MET+ group. The frequency of symptomatic intracerebral hemorrhages did not differ between groups. HbA1c levels were well-balanced between the groups. Patients with stroke and diabetes on treatment with MET receiving IVT had less severe strokes on admission and a better functional outcome at 3 months. This suggests a protective effect of MET resulting in less severe strokes as well as beneficial thrombolysis outcome.

Thrombolysis Before Thrombectomy in Acute Large Vessel Occlusion: a Risk/Benefit Assessment and Review of the Evidence

Recent evidence has shown an overwhelming benefit of mechanical thrombectomy for acute anterior circulation large vessel occlusion (LVO). Whether there is any additional benefit of IV tPA treatment prior to thrombectomy over thrombectomy alone is unproven in randomized trials. In this review, we summarize the available evidence for and against pre-thrombectomy treatment with IV tPA. In clinical trials demonstrating efficacy of thrombectomy, the majority of included patients were eligible for (and treated with) IV tPA. Systemic thrombolysis prior to thrombectomy is fraught with potential disadvantages: delay in thrombectomy, increased risk of systemic hemorrhagic complications and angioedema, and limitation of endovascular treatment options in patients who require more vigorous antithrombotic treatment (for instance due to stent placement). Two randomized clinical trials comparing outcomes of patients treated with IV tPA + thrombectomy versus thrombectomy alone have recently reported their outcomes. The DIRECT-MT investigators found no difference in functional outcomes or mortality among patients pre-treated with IV tPA prior to thrombectomy, while the SKIP investigators found similar rates of good functional outcome and mortality between treatment groups--although they failed to demonstrate non-inferiority. The limitations of these trials are reviewed here. Therefore, much of our understanding relies on indirect comparisons between patient groups, whereby patients treated with IV tPA + thrombectomy were compared with IV tPA-ineligible patients who underwent thrombectomy alone. Limited meta-analysis data suggest equipoise between combination therapy over a direct-to-thrombectomy approach for patients with acute LVO who meet criteria for IV tPA. Further confounding the picture is the emergence of IV tenecteplase as a potentially superior alternative to alteplase as a pre-thrombectomy systemic lytic agent in patients with LVO. While thrombectomy offers a more effective means of reperfusion in acute LVO compared with IV tPA alone, definitive evidence is lacking that thrombectomy without prior IV thrombolysis is equivalent (or superior) to thrombectomy preceded by IV tPA. While recent trial evidence has suggested non-inferiority of direct MT, given that IV thrombolysis has been established as a standard of care in acute ischemic stroke, IV tPA should be given in all eligible patients with disabling deficits for whom thrombectomy is not immediately available. Results of further, ongoing randomized trials will hopefully clarify what (if any) additional benefit there is for intravenous thrombolysis prior to thrombectomy, in what subgroups (if any) withholding IV thrombolysis prior to MT is beneficial, and furthermore, which agent (alteplase or tenecteplase) is the optimal drug for this indication.

Intravenous thrombolysis in patients with chronic kidney disease: A systematic review and meta-analysis.

To determine the association of chronic kidney disease (CKD) with the safety and efficacy of IV thrombolysis (IVT) among patients with acute ischemic stroke (AIS). A systematic review and pairwise meta-analysis of studies involving patients with CKD undergoing IVT for AIS were conducted to evaluate the following outcomes: symptomatic intracranial hemorrhage (sICH), asymptomatic and any intracranial hemorrhage (ICH), in-hospital and 3-month mortality, 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] score 0-1), and 3-month functional independence (FI, mRS score 0-2). CKD was defined with estimated glomerular filtration rate (eGFR) ranging from mild (eGFR 60-89 mL/min) to moderate (eGFR 30-59 mL/min) to severe (eGFR 15-29 mL/min). We identified 20 studies comprising 60,486 patients with AIS treated with IVT. In unadjusted analyses, CKD was associated with sICH according to the National Institute of Neurological Disorders and Stroke (NINDS) (7 studies; odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19-1.67) and European Cooperative Acute Stroke Study (ECASS) II (9 studies; OR 1.37, 95% CI 1.01-1.85) definitions, any ICH (8 studies; OR 1.42, 95% CI 1.18-1.70), 3-month mortality (9 studies; OR 2.20, 95% CI 1.72-2.81), 3-month FFO (8 studies; OR 0.58, 95% CI 0.47-0.72), and 3-month FI (8 studies; OR 0.57, 95% CI 0.46-0.71). In adjusted analyses, CKD was associated with sICH according to NINDS (4 studies; ORadj 1.34, 95% CI 1.01-1.79) and ECASS II (3 studies; ORadj 2.08, 95% CI 1.27-3.43) definitions, any ICH (6 studies; ORadj 1.41, 95% CI 1.01-1.97), in-hospital mortality (2 studies; ORadj 1.19, 95% CI 1.09-1.30), and 3-month FFO (6 studies; ORadj 0.80, 95% CI 0.70-0.92). After adjustment for confounders in this pairwise meta-analysis, moderate to severe CKD is associated with increased risks of ICH and worse functional outcomes among patients with AIS treated with IVT.

Outcome of patients with large vessel occlusion in the anterior circulation and low NIHSS score.

Optimal management of patients with large vessel occlusion (LVO) and low NIHSS score is unknown, which was the aim to investigate in this study. This is a retrospective analysis of a prospective single tertiary care centre 14-year cohort of patients with LVO in the anterior circulation and NIHSS score ≤ 5 on admission. Outcome was analysed according to primary intended therapy. Among 185 patients (median age 67.4years), 52.4% received primary conservative therapy (including 26.8% secondary reperfusion in case of secondary neurological deterioration), 12.4% IV thrombolysis (IVT) only and 35.1% primary endovascular therapy (EVT). 95 (51.4%) patients experienced neurological deterioration until 3months. Primary-IVT-only and primary-EVT compared to conservative-therapy patients had better 3months' outcome (54.5% vs. 30.8%: adjustedOR 6.02; adjustedp = 0.004 for mRS 0-1 and 54.7% vs. 30.8%: adjustedOR 5.09; adjustedp = 0.002, respectively). Also mRS shift analysis favored primary-IVT-only and primary-EVT patients (adjustedOR 6.25; adjustedp = 0.001 and adjustedOR 3.14; adjustedp = 0.003). Outcome in primary-IVT-only vs. primary-EVT patients did not differ significantly. Patients who received secondary EVT because of neurological deterioration after primary-conservative-therapy had worse 3months' outcome than primary-EVT patients (20.8% vs. 30.8%: adjustedOR 0.24; adjustedp = 0.047 for mRS 0-1 and adjustedOR 0.31; adjustedp = 0.019 in mRS shift analysis). Survival and symptomatic intracranial haemorrhage did not differ amongst groups. Our data indicate that primary IVT and/or EVT may be better than primary conservative therapy in patients with LVO in the anterior circulation and low NIHSS score. Furthermore, primary EVT was better than secondary EVT in case of neurological deterioration. There is an unmet need for RCTs to find the optimal therapy for this patient group.

Missing outcome data management in acute stroke trials testing iv thrombolytics. Is there risk of bias?

Missing outcome data may undermine interpretation of randomised clinical trials by weakening power and limiting apparent effect size. We assessed bias and inefficiency of two imputation methods commonly used in stroke trials evaluating the efficacy of iv thrombolysis. We searched the virtual international stroke trials archive (VISTA)-acute for ischaemic stroke patients with 90-day modified Rankin scale as an outcome, and known thrombolysis status. We excluded any with missing 30-day modified Rankin scale. We planned two analyses; first, we calculated odds ratios for outcome in thrombolysed versus not thrombolysed from imputed-only data, (a) among patients with missing modified Rankin scale 90 and (b) among matched patients with intact data (using propensity score methods and relevant covariates). Imputation approaches were last observation carried forward (LOCF) or multiple imputation. Outcome comparisons used dichotomisation and shift analysis. Thereafter, we calculated whole-population odds ratios using LOCF and multiple imputation (also through dichotomisation and shift analysis); first with the original 1.5% missing outcome data, and then artificially increasing the burden (5%; 10%; 20%; 30%). We considered 9657 patients from eight of the studies included in VISTA, 3034 (31%) thrombolysed. Missing data replacement by LOCF with analysis by dichotomisation gave the highest estimate of thrombolysis influence. Imputing while increasing the burden of missing data progressively raised the odds ratios estimates, though thresholds for overestimation were 10% for LOCF; 20% for multiple imputation.Discussion: Replacing missing outcome data tended to overestimate differences of thrombolysed versus non-thrombolysed patients, but had minimal impact below a 10% burden of missing data.Conclusion: In the specific context of acute stroke trials testing iv thrombolytics, replacing missing data by carrying forward the last observation tended to overestimate treatment odds ratios more than multiple imputation.

Abstract 115: Current Status of Acute Stroke Management in Korea: A Nationwide Report Based on 19,608 Patients Treated in 216 Hospitals

Introduction: There have been few reports on status of acute stroke management at a national level worldwide, and none in Korea. This study is aimed to describe the current status and disparities of acute stroke management in Korea. Methods: Data from 5th (2013) and 6th (2014) national surveys for assessing quality of acute stroke care were used. Patients with principal diagnosis codes indicating subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), ischemic stroke (IS), who were admitted via emergency rooms within 7 days of onset at hospitals treating 10 or more stroke cases during the each 3-month survey period were selected. Results: A total of 19,608 stroke cases (age, 67.7±13.5years; female, 45%; IS, 76%; ICH, 15%; SAH, 9%) treated in 216 hospitals were analyzed. Thirty-one percent of hospitals had stroke units and 41% of stroke cases were treated at hospitals without stroke units. In IS, IV thrombolysis (IVT) and endovascular treatment (EVT) rates were 10.7% and 3.6%, respectively. Thirty-nine percent of IVT and fifty-two percent of EVT cases were performed in hospitals with annual volume of &lt;25 IVT and &lt;15 EVT. Centralization of EVT showed disparities by region (Figure). Carotid endarterectomy, carotid artery stenting, decompressive, bypass surgery was conducted in 0.2%, 1.4%, 1.0%, 0.2% of IS cases; decompressive surgery was done in 28.1% of ICH cases; surgical clipping, endovascular coiling was done in 17.2%, 14.3% of SAH cases, respectively. There were noticeable regional disparities in various interventions, use of ambulance, arrival time and provision of stroke unit service. Conclusions: This study is the first report on the status of acute stroke care in Korea on a national level. Large number of recanalization therapies were performed in low-volume-hospitals. Expansion of stroke unit service, stroke center certification or accreditation, and connections between stroke centers and EMS are highly recommended.

Safety and efficacy of dual antiplatelet pretreatment in patients with ischemic stroke treated with IV thrombolysis: A systematic review and meta-analysis.

Conflicting data exist on the safety and efficacy of IV thrombolysis (IVT) in patients with acute ischemic stroke (AIS) receiving dual antiplatelet pretreatment (DAPP). The aim of the present systematic review and meta-analysis is to assess the safety and outcome of DAPP history among patients with AIS treated with IVT. We performed a comprehensive literature review to identify studies that investigated the safety and efficacy of DAPP among patients with AIS treated with IVT. We identified 9 studies comprising 66,675 patients. In unadjusted analyses, DAPP was associated with a higher likelihood of pooled symptomatic intracranial hemorrhage (sICH; odds ratio [OR] 2.26; 95% confidence interval [CI] 1.39-3.67) and 3-month mortality (OR 1.47; 95% CI 1.25-1.73). DAPP was also related to higher odds of sICH according to Safe Implementation of Treatments in Stroke Monitoring Study (OR 2.71; 95% CI 2.05-3.59), European Cooperative Acute Stroke Study II (OR 2.23; 95% CI 1.46-3.40), and National Institute of Neurological Disorders and Stroke (OR 1.59, 95% CI 1.38-1.83) definitions. There was no association between DAPP and 3-month favorable functional outcome (FFO, modified Rankin Scale [mRS] score 0-1) and 3-month functional independence (FI; mRS score 0-2). In adjusted analyses, history of DAPP was not associated with pooled sICH (OR 2.03; 95% CI 0.75-5.52), 3-month mortality (OR 1.11; 95% CI 0.87-1.40), 3-month FFO (OR 0.92; 95% CI 0.77-1.09), and 3-month FI (OR 1.01; 95% CI 0.89-1.15). After adjustment for potential confounders, DAPP appears not to be associated with higher risk of adverse outcomes in patients with AIS treated with IVT.

Thrombolysis for acute ischemic stroke in the unwitnessed or extended therapeutic time window.

To assess the utility of IV thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS) with unclear symptom onset time or outside the 4.5-hour time window selected by advanced neuroimaging. We performed random-effects meta-analyses on the unadjusted and adjusted for potential confounders associations of IVT (alteplase 0.9 mg/kg) with the following outcomes: 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores 0-1), 3-month functional independence (FI; mRS scores 0-2), 3-month mortality, 3-month functional improvement (assessed with ordinal analysis on the mRS scores), symptomatic intracranial hemorrhage (sICH), and complete recanalization (CR). We identified 4 eligible randomized clinical trials (859 total patients). In unadjusted analyses, IVT was associated with a higher likelihood of 3-month FFO (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.12-1.96), FI (OR 1.42, 95% CI 1.07-1.90), sICH (OR 5.28, 95% CI 1.35-20.68), and CR (OR 3.29, 95% CI 1.90-5.69), with no significant difference in the odds of all-cause mortality risk at 3 months (OR 1.75, 95% CI 0.93-3.29). In the adjusted analyses, IVT was also associated with higher odds of 3-month FFO (adjusted OR [ORadj] 1.62, 95% CI 1.20-2.20), functional improvement (ORadj 1.42, 95% CI 1.11-1.81), and sICH (ORadj 6.22, 95% CI 1.37-28.26). There was no association between IVT and FI (ORadj 1.61, 95% CI 0.94-2.75) or all-cause mortality (ORadj 1.75, 95% CI 0.93-3.29) at 3 months. No evidence of heterogeneity was evident in any of the analyses (I 2 = 0). IVT in patients with AIS with unknown symptom onset time or elapsed time from symptom onset >4.5 hours selected with advanced neuroimaging results in a higher likelihood of CR and functional improvement at 3 months despite the increased risk of sICH.

Outcomes of patients with stroke treated with thrombolysis according to prestroke Rankin Scale scores.

It is common practice to withhold IV thrombolysis (IVT) for acute ischemic stroke in patients with preexisting disabilities. To test the hypothesis of an association of IVT and good clinical outcome also in patients with preexisting disabilities without an increase in mortality, we analyzed data from 52,741 patients (15,317 treated with IVT) depending on prestroke Rankin Scale (pRS) score. We performed an observational study based on a consecutive stroke registry covering 10.8 million inhabitants. The outcome at discharge of patients with stroke admitted in the time window of potential eligibility for IVT (<4.5 hours after stroke onset) was compared between patients treated and those not treated with thrombolysis, stratified by pRS score. Logistic regression analysis was used to estimate adjusted odds ratios (ORs) along with 95% confidence intervals (CIs) for favorable clinical outcome, defined as returning to the baseline pRS score or a score of 0 or 1 and mortality. Sensitivity analyses for subgroups of mildly and severely affected patients with stroke were performed, and the influence of treatment duration was assessed. Among included patients, IVT rates were 32% for patients with pRS scores of 0 to 1 and 20% for patients with pRS scores of 2 to 5. IVT in patients with pRS scores of 0 to 4 was associated with a higher chance of returning to the baseline pRS score (or a modified Rankin Scale score of 0/1), with ORs ranging between 1.42 (pRS score 2; 95% CI 1.16-1.73) and 1.73 (pRS score 0; 95% CI 1.61-1). The OR observed in patients with a pRS score of 5 was 0.65 (95% CI 0.25-1.70). Observed associations remained consistent in sensitivity analyses. Subgroup analyses revealed no evidence of bias due to potential floor and ceiling effects. No evidence of elevated in-hospital mortality of patients treated with thrombolysis was observed. Our study suggests that IVT can be effective even in patients with severe preexisting disabilities, provided that they were not bedridden before stroke onset. Withholding IVT on the sole ground of prestroke disabilities may not be justified.

Outcome of endovascular therapy in stroke with large vessel occlusion and mild symptoms.

To compare outcomes after endovascular therapy (EVT) and IV thrombolysis (IVT) in patients with stroke with emergent large vessel occlusion (LVO) and mild neurologic deficits. This was a retrospective analysis of patients from the Swiss Stroke Registry with admission NIH Stroke Scale score ≤5 and LVO treated by EVT (± IVT) vs IVT alone. The primary endpoint was favorable functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months. Secondary outcomes were independence (mRS score 0-2), mRS score (ordinal shift analysis), and survival with high disability (mRS score 4-5). Safety endpoints were mortality and symptomatic hemorrhage. Of 11,356 patients, 312 met the criteria and propensity score method matched 108 in each group. A comparably large proportion of patients with EVT and IVT had favorable outcome (63% vs 65.7% respectively; odds ratio 0.94, 95% confidence interval 0.51-1.72; p = 0.840). Patients with EVT showed a nonsignificant trend toward higher mRS score at 3 months (p = 0.717), while the proportion of surviving patients with high disability was comparably very low in both groups (p = 0.419). Mortality was slightly higher among those with EVT (9.3% vs 2.8%; p = 0.06), and symptomatic intracranial hemorrhage was a rare event in both groups (2.8% vs 0%; p = 0.997). In acute ischemic stroke, EVT and IVT appear similarly effective in achieving favorable outcome at 3 months for patients with LVO and mild neurologic symptoms. EVT might be marginally inferior to IVT regarding outcome across all levels of disability and mortality. Further studies are required to determine whether certain subgroups of patients with LVO and mild symptoms benefit from EVT. This study provides Class III evidence that patients with LVO and mild symptoms receiving either EVT or IVT had similar favorable functional outcomes at 3 months.