Safety Of Intravenous Thrombolysis Research Articles

Intravenous recombinant tissue plasminogen activator for acute ischemic stroke: a feasibility and safety study.

BackgroundIn developing countries, intravenous thrombolysis (IVT) is available at a limited number of centers. This study aimed to assess the feasibility and safety of IVT at Tabriz Imam Reza Hospital.MethodsIn a prospective study, over a 55-month period, any patient at the hospital for whom stroke code had been activated was enrolled in the study. Data on demographic characteristics, stroke risk factors, admission blood pressure, blood tests, findings of brain computed tomography (CT) scans, time of symtom onset, time of arrival to the emergency department, time of stroke code activation, time of CT scan examination, and the time of recombinant tissue plasminogen activator administration were recorded. National Institutes of Health Stroke Scale assessments were performed before IVT bolus, at 36 hours, at either 7 days or discharge (which ever one was earlier), and at 3-month follow-up. Brain CT scans were done for all patients before and 24 hours after the treatment.ResultsStroke code was activated for 407 patients and IVT was done in 168 patients. The rate of functional independence (modified Rankin Scale [mRS] 0–1) at 3 months was 39.2% (62/158). The mortality rate at day 7 was 6% (10/168). Hemorrhagic transformation was noted in 16 patients (9.5%). Symptomatic intracranial hemorrhage occurred in 5 (3%), all of which were fatal. One case of severe urinary bleeding and one other fatal case of severe angioedema were observed.ConclusionDuring the first 4–5 years of administration of IVT in the hospital, it was found to be feasible and safe, but to increase the efficacy, poststroke care should be more organized and a stroke center should be established.

Abstract TMP1: International Multicenter Study Demonstrating Safety of Intravenous Thrombolysis in Acute Ischemic Stroke Patients Harboring Unruptured Intracranial Aneurysms

Objective: We sought to determine the safety of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients harboring unruptured intracranial aneurysm (UIA) in a prospective, multi-center study. Methods: We prospectively analyzed data from consecutive AIS treated with IVT during a 4-year period at four tertiary-care stroke centers. All patients routinely underwent CT or MR angiography during hospitalization. The presence of UIA was documented on the basis of neuroradiology reports. Symptomatic intracranial hemorrhage (sICH) was defined as imaging evidence of ICH combined with an increase in NIHSS-score of ≥4 points. Results: Our multicenter study evaluated a total of 1398 AIS patients treated with IVT with available neurovascular imaging data. The presence of concomitant UIAs was identified in 42 cases (3.0%, 95%CI by adjusted Wald method: 2.2%-4.1%) harboring a total of 48 IAs. Four of the forty-two (8%) AIS patients had multiple aneurysms. The mean maximum diameter of UIA was 4.3±2.7mm ranging between 2-15 mm. Nearly all UIA were saccular (45/48, 94%) and the majority were located in the anterior circulation (29/48; 61%). The maximum diameter was ≥7mm and ≥10mm in 6 (12.5%) and 3 (6.3%) cases respectively. The rates of symptomatic and asymptomatic ICH were 2.4% (95%CI by adjusted Wald method: 0%-12.6%) and 7.1% (95%CI by adjusted Wald method: 1.8%-19.7%) respectively. The single sICH reported in our multi-center study was not caused by aneurysmal rupture, since the incidental aneurysm was located in the posterior communicating artery in the hemisphere that was contralateral to the sICH. The rates of in-hospital mortality and favorable functional outcome at hospital discharge (defined as modified Rankin Scale score of 0-1) were 2.4% (95%CI by adjusted Wald method: 0%-12.6%) and 50.0% (95%CI by adjusted Wald method: 35.5%-64.5%) respectively. Conclusions: Our prospectively collected multi-center data indicate the potential safety of IVT in AIS patients with UIA.

Antithrombotic therapy in acute ischemic stroke patients with atrial fibrillation

Atrial fibrillation (AF) is an independent risk factor that increases the risk of acute ischemic stroke by five-fold. In addition, it is also a significant predictor of stroke's poor outcome. The aim of this article was to provide an overview on current approach in AF associated stroke prevention and treatment. Oral anticoagulant therapy (OAC) is recommended for stroke prevention in AF patients. This includes either vitamin K antagonists (VKAs) or novel oral anticoagulants (NOACs). In primary prevention, by using risk stratification schemes, clinicians should identify low-risk AF patients who do not require antithrombotic therapy; all others are indicated for OAC. For secondary stroke prevention all AF patients should be offered OAC. The assessment of bleeding risk should also be performed in order to influence modifiable risk factors for bleeding. Intravenous thrombolysis (IVT) can probably be administrated safely in patients given VKAs if the international normalised ratio is less than 1.7, although bleeding risk is slightly raised. Data regarding safety of IVT used in patients on NOAC are very scarce, however, some coagulation parameters could help to identify those patients who might be eligible for thrombolysis. Stroke prevention is central to the management of AF. The use of OAC is recommended for stroke prevention. In the acute stroke phase, if patients are fully anticoagulated, by any medication, then IVT is contraindicated. However, it may be considered in some circumstances if the level of anticoagulation is subtherapeutic.

Intravenous Thrombolysis is Effective in Young Adults: Results from the Baden-Wuerttemberg Stroke Registry.

The efficacy of intravenous thrombolysis (IVT) is sufficiently proven in ischemic stroke patients of middle and older age by means of randomized controlled trials and large observational studies. However, data in young stroke patients ≤50 years are still scarce. In this study, we aimed to evaluate the effectiveness and safety of IVT in young adults aged 18-50 years. Data from a consecutive and prospective stroke registry was analyzed that covers a federal state with 10.8 million inhabitants in southwest Germany. Our analysis comprises 51,735 ischemic stroke patients aged 18-80 years and hospitalized from January 2008 to December 2012. Of these, 4,140 (8%) were aged 18-50 years and 7,529 (15%) underwent IVT. Data on 8,439 patients (16% of the study population) were missing for National Institutes of Health stroke severity score at admission and/or modified Rankin Scale (mRS) at discharge and were excluded from outcome analysis. In sensitivity analysis, patients with incomplete data were also examined. Binary logistic regression models were used adjusted for patient, hospital, and procedural parameters and stratified by age group (18-50 and 51-80 years, subgroup analyses 18-30, 31-40, and 41-50 years) to assess the relationship between IVT and mRS at discharge. IVT appears equally effective in young adults 18-50 years (adjusted odds ratio 1.40, 95% confidence interval 1.12-1.75; p = 0.003), compared to patients 51-80 years of age (1.33, 1.23-1.43; p < 0.001). Age-stratified analyses suggest an inverse relation of age and effectiveness, which appears to be highest in very young patients 18-30 years of age (2.78, 1.10-7.05; p = 0.03). Ischemic stroke etiology, vascular dynamics, and recovery in young patients differ from those of middle and older age. The evidence from routine hospital care in Germany indicates that IVT in young stroke patients appears to be at least equally effective as in the elderly.

Safety of Intravenous Thrombolysis among Stroke Patients Taking New Oral Anticoagulants—Case Series and Systematic Review of Reported Cases

Current guidelines do not recommend the administration of intravenous tissue plasminogen activator (IV-tPA) to patients with acute ischemic stroke (AIS) who take new oral anticoagulants (NOACs). We present a multicenter case series of IV-tPA use while the patients are on NOACs, as well as a systematic review of the literature. We reviewed the medical records of consecutive patients on NOACs who received IV-tPA for symptoms of AIS at four participating stroke centers in the United States and Europe. Safety endpoints were post-thrombolysis symptomatic intracranial hemorrhage (sICH) or other serious systemic bleeding. Between October 2010 and October 2014, 6 patients received IV-tPA for possible AIS while taking dabigatran. None of the patients had sICH or any other hemorrhagic complication. Literature review resulted in a total of 26 patients receiving IV-tPA while on NOACs (dabigatran: 15, rivaroxaban: 10, apixaban: 1). Among them, two patients experienced sICH and died. None of the patients experienced major extracranial hemorrhage; however, minor and asymptomatic hemorrhagic complications were described in 7 patients. Pooled analysis indicates an sICH rate of 6.45% (95% CI by the adjusted Wald method: .8-21.7%). The mean interval between the last dose of NOAC and IV thrombolysis was 12 ± 7.8 [4-28.3] hours. Although the safety of IV-tPA cannot be definitively confirmed in a small series, consideration of stroke severity and management of hemorrhage risk with general precautions with post-tPA management protocols can justify treatment in the absence of coagulopathy.

Is acute reperfusion therapy safe in acute ischemic stroke patients who harbor unruptured intracranial aneurysm?

Intracranial aneurysms are currently considered as contraindication for intravenous thrombolysis in acute ischemic stroke, very likely due to a possible increase in the risk of bleeding from aneurysm rupture; however, there is limited data available on whether intravenous thrombolysis is safe for acute ischemic stroke patients with pre-existing intracranial aneurysms. To find out the safety of intravenous thrombolysis in acute ischemic stroke patients who harbor unruptured intracranial aneurysms. We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with intravenous thrombolysis for acute ischemic stroke in our center from the beginning of 2006 till the end of April 2014. Those with unruptured intracranial aneurysm present on cerebrovascular images prior to acute reperfusion therapy were identified. Post-thrombolysis brain imaging was reviewed to evaluate for any intraparenchymal or subarachnoid hemorrhage related or unrelated to the aneurysm. A total of 637 patients received intravenous thrombolysis for acute ischemic stroke in our center during an 8·3-year period. Thirty-three (5·2%) were found to have at least one intracranial aneurysms. Twenty-three (70%) of those received only intravenous thrombolysis, and 10 patients received combination of intravenous and intra-arterial thrombolysis. The size of the largest aneurysm was 10 mm in maximum diameter (range: 2-10 mm). The mean size of aneurysms was 4·8 mm. No symptomatic intracranial hemorrhage occurred among the 23 patients receiving only intravenous thrombolysis. Out of those who received a combination of intravenous and intra-arterial thrombolysis, one developed symptomatic intracranial hemorrhage in the location of acute infarct, distant to the aneurysm location. Our findings suggest that neither intravenous thrombolysis nor combination of intravenous and intra-arterial thrombolysis increases the risk of aneurysmal hemorrhage in acute ischemic stroke patients who harbor unruptured intracranial aneurysms less than 10 mm in diameter. Their listing in exclusion criteria for intravenous thrombolysis should be reconsidered to assure appropriate use of acute reperfusion therapy in this group of patients.

Computed tomography perfusion-based thrombolysis in wake-up stroke.

Wake-up stroke (WUS) patients are typically excluded from reperfusion treatment, as the time of symptoms onset is unknown. The purpose of this study is to evaluate the clinical outcome and safety of intravenous thrombolysis with rt-PA in patients with WUS eligible for therapy using computed tomography perfusion criteria (CTP), compared to patients treated with rt-PA within 4.5 h of symptoms onset (non-WUS). This is an experimental, open-label trial, controlled against the best therapy currently in use. Primary endpoints were functional independence after 3 months [modified Rankin scale (mRS) ≤ 1] for clinical outcome and symptomatic intracerebral hemorrhage (SICH) for safety. Secondary endpoints were no or only mild disability after 3 months (mRS ≤ 2) for clinical outcome, total intracerebral hemorrhage (TICH) and contrast-induced nephropathy (CIN) for safety. 170 patients were treated, 143 non-WUS patients and 27 patients with WUS. Strokes of cardioembolic origin were most common in WUS patients (p < 0.001). Primary endpoints: mRS ≤ 1 was found in 35.8 % (non-WUS: 36.4% vs. WUS 33.3%; p = 0.62) and SICH was observed in 3.4 % of non-WUS patients and in WUS patients (p = 0.32). Secondary endpoints: mRS ≤ 2 was observed in 66.4 % of patients (non-WUS: 67.1% vs. WUS 62.9%; p = 0.67), TICH in 13.5 % of patients (13.9 % non-WUS vs. 11.1 % WUS; p = 0.69). CIN was documented in 3.7 % of WUS patients. rt-PA treatment carried out in WUS patients selected on the basis of CTP data demonstrate comparable clinical outcome and safety with respect to non-WUS patients. The study supports the hypothesis that a selected group of WUS patients may be suitable for thrombolysis.

Safety of Intravenous Thrombolysis in Stroke Mimics: Prospective 5-Year Study and Comprehensive Meta-Analysis: Tsivgoulis G, Zand R, Katsanos AH. Stroke 2015;46:1281-1287.

Safety of Intravenous Thrombolysis in Stroke Mimics: Prospective 5-Year Study and Comprehensive Meta-Analysis: Tsivgoulis G, Zand R, Katsanos AH. Stroke 2015;46:1281-1287.

Safety of intravenous thrombolysis in stroke mimics: prospective 5-year study and comprehensive meta-analysis.

Shortening door-to-needle time may lead to inadvertent intravenous thrombolysis (IVT) administration in stroke mimics (SMs). We sought to determine the safety of IVT in SMs using prospective, single-center data and by conducting a comprehensive meta-analysis of reported case-series. We prospectively analyzed consecutive IVT-treated patients during a 5-year period at a tertiary care stroke center. A systematic review and meta-analysis of case-series reporting safety of IVT in SMs and confirmed acute ischemic stroke were conducted. Symptomatic intracerebral hemorrhage was defined as imaging evidence of ICH with an National Institutes of Health Stroke scale increase of ≥4 points. Favorable functional outcome at hospital discharge was defined as a modified Rankin Scale score of 0 to 1. Of 516 consecutive IVT patients at our tertiary care center (50% men; mean age, 60±14 years; median National Institutes of Health Stroke scale, 11; range, 3-22), SMs comprised 75 cases. Symptomatic intracerebral hemorrhage occurred in 1 patient, whereas we documented no cases of orolingual edema or major extracranial hemorrhagic complications. In meta-analysis of 9 studies (8942 IVT-treated patients), the pooled rates of symptomatic intracerebral hemorrhage and orolingual edema among 392 patients with SM treated with IVT were 0.5% (95% confidence interval, 0%-2%) and 0.3% (95% confidence interval, 0%-2%), respectively. Patients with SM were found to have a significantly lower risk for symptomatic intracerebral hemorrhage compared with patients with acute ischemic stroke (risk ratio=0.33; 95% confidence interval, 0.14-0.77; P=0.010), with no evidence of heterogeneity or publication bias. Favorable functional outcome was almost 3-fold higher in patients with SM in comparison with patients with acute ischemic stroke (risk ratio=2.78; 95% confidence interval, 2.07-3.73; P<0.00001). Our prospective, single-center experience coupled with the findings of the comprehensive meta-analysis underscores the safety of IVT in SM.

Abstract W P52: Safety of Intravenous Thrombolysis (IVT) in Stroke Mimics: A Prospective Five-year Study and Comprehensive Meta-analysis of Reported Case Series

Background&amp;Purpose: Shortening door-to-needle time may lead to intravenous thrombolysis (IVT) administration in stroke mimics (SM). We sought to determine safety of IVT in SM using prospective, single-center data and by conducting a comprehensive meta-analysis of reported case series. Subjects&amp;Methods: We analyzed consecutive IVT-treated patients during a 5-year period (2009-2013) at a tertiary care stroke center. Non-contrast head CT, NIHSS pre-treatment and modified Rankin scores (mRS) at discharge were obtained as standard of care. SM was defined as no acute ischemic lesions on MRI and the final non-stroke diagnosis established by radiologists and treating physicians unaware of the purposes of this study. Symptomatic intracerebral hemorrhage (sICH) was defined as imaging evidence of ICH with NIHSS increase of 4 or more points. Functional independence (FI) was defined as mRS 0-1. We also conducted a comprehensive meta-analysis of all available case-series reporting safety of IVT in SM using PRISMA guidelines. Results: Of 516 consecutive IVT patients at our tertiary care center (50% men; mean age 60±14years; median NIHSS 11, range 3-22), SM comprised 75 cases (14.5%, 95%CI by adjusted wald method: 11.7%-17.9%). sICH occurred in one patient (1.3%; 95%CI:0%-7.9%), while we documented no cases of orolingual edema (OE) or major extracranial hemorrhagic complications (0%; 95%CI:0%-4.2%). Two patients experienced minor extra-cranial hemorrhagic complications (1 case of gingival &amp; 1 case of nose bleeding). Meta-analysis of 9 studies including 8,942 patients treated with IVT and reporting safety outcomes in 392 SM showed pooled rates of sICH and OE 0.5% (95%CI: 0%-2%) and 0.3% (95%CI: 0%-2%) respectively. We documented no heterogeneity between estimates of sICH (I squared statistic=0%; p=0.941 Cohran Q test), and OE (I squared statistic=0%; p=0.913 Cohran Q test). Conclusions: Our prospectively collected data coupled with the findings of the comprehensive meta-analysis underscore the safety of IVT in SM given the low prevalence of hemorrhagic and systemic complications and the lack of heterogeneity across reported case-series.

Abstract 161: Safety of Intravenous Thrombolysis in Wake-up Stroke: A Multicenter, Prospective, Open-label Study

Background and Objectives: A significant number of ischemic strokes are noticed upon awakening and are not candidates for intravenous recombinant tissue plasminogen activator (rtPA) due to &gt;3 hours from last seen normal (LSN). We tested the safety of rtPA in a multicenter, single-arm, prospective, open-label study (NCT01183533) of rtPA in patients with wake-up stroke (WUS). Methods: We aimed to enroll 40 WUS patients with disabling deficits. Patients were 18-80; NIHSS ≤25; and selected only on the appearance of non-contrast CT (i.e., &lt;1/3 MCA territory hypodensity). Standard dose (0.9mg/kg) intravenous rtPA had to be started ≤3 hours of awakening. The primary safety outcome was symptomatic intracerebral hemorrhage (ICH) with pre-planned stopping rules and data safety board oversight. Other endpoints included: asymptomatic ICH, clinical improvement in NIHSS and 90-day modified Rankin Scale score (mRS). Results: Between 10/2010 and 10/2013, all pre-planned patients were enrolled. Four patients (10%) were subsequently determined to be mimics. Baseline characteristics, treatment and outcome data are shown in the table. No symptomatic ICH or parenchymal hematomas occurred. Conclusion: Intravenous thrombolysis appears to be safe in WUS patients selected by non-contrast CT. A randomized effectiveness trial appears feasible using a similar, pragmatic design.

Intravenous versus intra-arterial thrombolysis in ischemic stroke: a systematic review and meta-analysis.

BackgroundReperfusion following ischemic stroke can be attained by either intravenous thrombolysis (IVT) or intra-arterial thrombolysis (IAT). Only a limited number of randomized prospective studies have compared the efficacy and safety of IVT and IAT. This meta-analysis investigated possible clinical benefits of IAT relative to IVT in patients with acute ischemic stroke.MethodsWe searched the PubMed, Cochrane, and Google Scholar databases through October 2013 for manuscripts that describe the findings of randomized controlled or prospective studies that evaluated the outcomes of patients with ischemic stroke who were treated with IVT or IAT. The clinical outcome measures were score on the modified Rankin scale (mRS) and mortality at 90 days. A favorable outcome was defined as an mRS score of 0 to 2.ResultsFor the mRS, the combined odds ratio (OR) of 3.28 (95% confidence interval (CI), 1.91 to 5.65, P < 0.001) indicated that patients who received IAT had a significantly higher chance for a favorable outcome than did those who received IVT. For mortality, the OR indicated that IAT therapy significantly reduced the proportion of patients who died within 90 days of the procedure (combined OR, 0.40; 95%CI, 0.17 to 0.92; P = 0.032).ConclusionThis meta-analysis determined that IAT conferred a significantly greater probability of achieving a favorable outcome compared with IVT. There was also a significant difference in mortality rates between IAT and IVT. The studies included in this analysis were small and heterogeneous; therefore, larger randomized prospective clinical studies are necessary to further investigate this issue.

Chronic kidney disease and bleeding complications after intravenous thrombolytic therapy for acute ischemic stroke.

The safety of intravenous thrombolysis in ischemic stroke (IS) patients with chronic kidney disease (CKD) is uncertain. We assessed whether CKD is associated with bleeding complications after intravenous tissue-type plasminogen activator administration to patients with IS. Data were analyzed from 44 410 patients with IS treated with intravenous tissue-type plasminogen activator in the Get With The Guidelines-Stroke Program. Glomerular filtration rate based on admission serum creatinine was categorized as dichotomous (presence of CKD as <60) or as distinct categories: normal (≥90), mild (≥60-<90), moderate (≥30-< 60), severe (≥15-<30), and kidney failure (<15 or dialysis). Primary outcomes evaluated were symptomatic intracranial hemorrhage and serious systemic hemorrhage; secondary outcomes were in-hospital mortality, independent functional status. There were 15 191 of 44 410 (34%) intravenous tissue-type plasminogen activator-treated IS patients with CKD. Presence of CKD (versus no CKD) was not associated with risk-adjusted symptomatic intracranial hemorrhage (adjusted odds ratio, 1.0; 95% confidence interval: 0.91-1.10) or serious systemic hemorrhage (adjusted odds ratio, 0.97; 95% confidence interval: 0.80-1.18) and did not significantly vary by kidney dysfunction stage for either of these primary end points in multivariable analyses. Compared with patients with normal kidney function, those with CKD were more likely to die in the hospital (adjusted odds ratio, 1.22; 95% confidence interval: 1.14-1.32) and have an unfavorable discharge functional status (adjusted odds ratio, 1.13; 95% CI: 1.07-1.19). Presence of CKD among patients with IS treated with intravenous tissue-type plasminogen activator is associated with higher unadjusted odds of symptomatic intracranial hemorrhage or serious systemic hemorrhage, but this is explained by non-CKD related factors.

THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg (THAWS) Trial.

RationaleBecause of lack of information regarding timing of stroke, patients who suffer stroke during sleep are generally ineligible for intravenous thrombolysis, although many of these patients could potentially recover with this treatment. Magnetic resonance image findings with positive diffusion-weighted imaging and no marked parenchymal hyperintensity on fluid-attenuated inversion recovery (negative pattern) can identify acute ischemic stroke patients within 4·5 h from symptom onset.AimsThe THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg trial aims to determine the efficacy and safety of intravenous thrombolysis with alteplase at 0·6 mg/kg body weight, the approved dose for Japanese stroke patients, using magnetic resonance image-based selection in ischemic stroke patients with unclear time of symptom onset, and compare findings with standard treatment.DesignThis is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-end-point clinical trial. The design is similar to the Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke trial. Patients with unclear-onset time of stroke symptoms beyond 4·5 h and within 12 h after the time of the last-known-well period and within 4·5 h after symptom recognition, who showed a negative fluid-attenuated inversion recovery pattern, are randomized to either intravenous thrombolysis or standard treatment.Study outcomesThe primary efficacy end-point is modified Rankin Scale 0–1 at 90 days. The safety outcome measures are symptomatic intracranial hemorrhage at 22–36 h, and major bleeding and mortality at 90 days.DiscussionThis trial may help determine if low-dose alteplase at 0·6 mg/kg should be recommended as a routine clinical strategy for ischemic stroke patients with unclear-onset time.

Effect of Intravenous Thrombolysis on Stroke Associated with Atrial Fibrillation

Data based on randomized clinical trials regarding the efficacy and safety of intravenous thrombolysis (IVT) versus placebo or any other antithrombotic agent in the treatment of stroke associated with atrial fibrillation (AF) are unavailable. Prospectively collected data on AF-associated stroke patients treated in a 3-year period were analyzed to assess the effect of IVT treatment. Outcome measures were modified Rankin Scale (mRS) score for functional outcome, death, and symptomatic intracerebral hemorrhage (sICH). Of 787 patients diagnosed with an acute ischemic stroke in the observed period, 131 (16.6%) had AF. Multivariate logistic regression analysis after adjustment for confounders demonstrated that independent predictors of excellent outcome (mRS 0-1) in patients with AF-associated stroke were lower baseline National Institutes of Health Stroke Scale [NIHSS] score (adjusted odds ratio [(adj)OR], .87; 95% confidence interval [CI], 0.81-.94; P = .000) and the use of IVT ((adj)OR, 5.31; 95% CI, 1.90-14.82; P = .001), whereas independent predictors of death were higher baseline NIHSS score ((adj)OR, 1.07; 95% CI, 1.02-1.12; P = .003), previous stroke ((adj)OR, 4.11; 95% CI, 1.49-11.35; P = .006), absence of IVT use ((adj)OR, .19; 95% CI, .05-.77; P = .021), sICH ((adj)OR, 18.52; 95% CI, 1.59-215.37; P = .020), and higher serum glucose levels ((adj)OR, 1.26; 95% CI, 1.06-1.50; P = .008). Thrombolyzed patients with AF were less severe at baseline and were less likely to have NIHSS >18. They were more likely to have excellent and good functional outcome (mRS 0-2) whereas less likely to have death as outcome at 3 months. Thrombolyzed AF patients had constantly lower probability of death regardless of the baseline NIHSS score values. These results should encourage the use of IVT in AF-associated strokes.

Abstract T P48: Intravenous Thrombolysis Using Low-Dose Alteplase for Nonagenarians with Acute Ischemic Stroke: The SAMURAI rtPA Registry

Objective: Although intravenous thrombolysis (IVT) using alteplase for octogenarians with acute ischemic stroke becomes relatively familiar, it is unclear whether IVT for nonagenarians is a futile intervention. The purpose of this study is to clarify the efficacy and safety of IVT using low-dose alteplase (0.6 mg/kg) for nonagenarians compared with octogenarians. Methods: Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rtPA registry retrospectively collected 600 consecutive acute stroke patients receiving IVT from 10 Japanese stroke centers between October 2005 and July 2008. We extracted all octogenarians (O group) and nonagenarians (N group) from the registry. We compared baseline characteristics, symptomatic intracranial hemorrhage (SICH), and 3-month outcomes between the groups. 3-month outcomes include; functional independence (FI) defined as a mRS score 0-2, good outcome (GO) as a mRS score 0-2 or same as the premorbid mRS, poor outcome (PO) defined as a mRS score 5-6, and death. Results: Twenty-five nonagenarians (mean age, 93 years) and 124 octogenarians (mean age, 84 years) were included. N group was more female-predominant (76% versus 56%, p=0.06) and premorbidly dependent (44% versus 14%, p&lt;0.001) than O group. There were no significant differences of median baseline NIHSS score (16 versus 14, p=0.95) and Alberta Stroke Program Early CT Score (9 versus 9, p=0.36) between the groups. The rate of FI tended to be lower in N group than O group (16% versus 36%, p=0.06), otherwise, the differences of the rates of GO (28% versus 37%, p=0.39), PO (40% versus 36%, p=0.73), death (20% versus 11%, p=0.23) and SICH (0% versus 2.4%, p=1.00) were not significant between the groups. In comparison with O group, N group was not associated with 3-month clinical outcomes (FI; OR 0.61; 95% CI, 0.15-2.42, GO; 0.98; 0.31-3.07, PO; 0.63; 0.15-2.70, death; 3.18; 0.62-16.3) and SICH (0.68; 0.17-2.69) after multivariate adjustment. Conclusions: IVT using low-dose alteplase for N group resulted in less frequent achievement of FI mainly because of more premorbid dependency than O group, however, showed at least a similar safety and a potential efficacy.

Computed Tomography Angiography before Intravenous Thrombolysis Does Not Increase the Risk of Renal Dysfunction

Our aim is to determine whether computed tomography angiography (CTA) before intravenous thrombolysis (IVT) affects renal function in acute ischemic stroke (AIS) patients. We performed an observational analysis of AIS patients treated with IVT for three years. Patients were classified into 2 groups: those who underwent CTA (CTA-group) and those who did not (control-group). Differences in creatinine levels between baseline and 24–72 hours after IVT were calculated. Acute renal dysfunction (ARD) was defined as an increase in serum creatinine level of ≥0.5 mg/dL and/or ≥25% above baseline within 24–72 hours after IVT. 190 patients were treated with IVT. Renal function (before and after IVT) was assessed in 162 (115 in control-group; 47 in CTA-group). Nine patients (5.5%) developed ARD (2 (4.2%) in CTA-group and 7 (6.1%) in control-group; P=0.6). CTA was not associated with a higher risk of ARD and did not affect the efficacy or safety of IVT. Previous chronic renal insufficiency, baseline creatinine levels, and previous use of nonsteroidal anti-inflammatory drugs were associated with a significant increase in creatinine levels, independently of contrast use. In conclusion, CTA does not seem to increase the risk of renal dysfunction. This technique may be used safely without knowledge of baseline creatinine levels.

Safety of thrombolysis with IV rt-PA in patients with atrial fibrillation related ischemic strokes and prior subtherapeutic use of coumarinic anticoagulants

Background and purpose. There are conflicting data in the literature regarding the safety of intravenous thrombolysis in patients with ischemic strokes receiving prior treatment with vitamin K antagonists. We aimed to assess the safety, short term outcome and mortality after rt-PA administration in patients with atrial fibrillation related strokes and prior subtherapeutic use of vitamin K antagonists. Methods. The study included 210 patients with atrial fibrillation who received treatment with intravenous rt-PA for acute ischemic stroke. We compared the frequency of bleeding complications, including intracerebral hemorrhage of any type and symptomatic intracerebral hemorrhage in patients with and without preadmission acenocoumarol use. We also investigated whether there were differences regarding short term functional outcome (assessed with the modified Rankin score at three months after thrombolysis) and mortality rates between them. Results. 48 patients (22.8%) were receiving acenocoumarol before admission and had international normal ratio (INR) ≤ 1.7. In this group, the median INR value was 1.4 (IQR 1.3-1.6). Preadmission coumarinic anticoagulants use was neither associated with secondary intracerebral hemorrhage of any type (p = 0.9), nor with symptomatic intracerebral hemorrhage (p = 0.9). Moreover, no differences regarding short term stroke outcome (p = 0.86), and mortality (p = 0.56) were observed between patients with or without prior acenocoumarol use. Using logistic regression analysis NIHSS score was found to be the only independent predictor for both short term stroke outcome (OR = 0.82; 95% CI 0.77-0.87; p &lt; 0.0001) and mortality (OR = 1.18; 95%CI 1.09-1.27; p &lt; 0.0001). Chronic heart failure was a second independent predictor for mortality (OR = 3.66; 95%CI 1.41-9.5; p = 0.007). Blood pressure values of more than 185/110 mmHg during the first 24 hours after stroke onset were independently associated with the short term stroke outcome (OR 0.37; 95% CI 0.15-1.88; p = 0.02). Conclusion. In the present study the rates of intracranial hemorrhage and mortality following intravenous thrombolysis for atrial fibrillation related ischemic strokes were not different between the patients who were prior receiving subtherapeutic treatment with acenocoumarol and those who were not receiving coumarinic oral anticoagulants at all. As a result, the use of recombinant tissue plasminogen activator in this clinical setting seems to be safe. Further studies with larger number of patients and a prospective design are needed to confirm these findings.

CT Angiography in an Acute Stroke Protocol: Correlation between Occlusion Site and Outcome of Intravenous Thrombolysis

Thrombolysis with intravenous rt-PA is the current therapy for acute ischemic stroke. Unlike other outcome factors, relatively little is known about the prognostic value of the occlusion site on treatment outcome. We compared the effectiveness and safety of intravenous thrombolysis in patients with different levels of occlusion identified by CT angiography (CTA) in anterior circulation stroke, and analyzed the influence of the occlusion site on treatment outcome in relation to other outcome factors. We selected 71 patients from a stroke database collected between June 2007 and December 2011 at our hospital. All of the studied patients had anterior circulation stroke with intracranial occlusion detected by CTA and were treated with intravenous rt-PA. They were divided into two groups according to the site of occlusion along the middle cerebral artery course: proximal (carotid "T", complete M1 and mild M1 occlusions) and distal (M2/M3 occlusions). Treatment effectiveness was assessed by modified Rankin Scale (mRS) at three months, considering a positive outcome a mRS value ≤ 2. Treatment safety was assessed by evaluating the rate of hemorrhagic complications seen on unenhanced CT at 24 hours. Binary logistic regression was performed to evaluate the interaction between occlusion site and other variables such as sex, age, ASPECT score on admission and baseline NIHSS value in determining treatment outcome. The degree of effectiveness and safety differed when considering patients with proximal and distal occlusions. The percentage of successfully treated cases was 28.6% in the first group compared to 72% in the second, and the rate of hemorrhagic complications was 28.6% and 6% respectively. After adjustment for sex, age, ASPECT score on admission and baseline NIHSS value, occlusion site was the only variable significantly influencing treatment safety and, together with baseline NIHSS value, the only valid predictor of treatment effectiveness. We demonstrated a correlation between the site of arterial occlusion and outcome of intravenous thrombolysis. By helping the choice of the best therapeutic strategy depending on the identified occlusion site, CTA could be usefully added to the examinations included in the Stroke Protocol for the baseline evaluation of patients with suspected acute stroke.

Abstract TMP24: Intravenous Thrombolysis For Acute Ischemic Stroke Occurring During Hospitalization For Transient Ischemic Attack: An International, Multicenter Study

Background&amp;Purpose: There are limited data regarding the safety of intravenous thrombolysis (IVT) in patients who experienced acute ischemic stroke (AIS) during their hospitalization for Transient Ischemic Attack (TIA). We sought to prospectively evaluate the safety and efficacy of systemic thrombolysis in AIS occurring during hospitalization for TIA in an international, multi-center study Subjects&amp;Methods: Consecutive patients with AIS that occurred during hospitalization for prior TIA were treated with standard intravenous tissue plasminogen activator (tPA) at five tertiary-care stroke centers. Early arterial recanalization was determined by transcranial Doppler at the end of tPA infusion using the previously validated Thrombolysis in Brain Ischemia flow-grading system. Symptomatic intracranial hemorrhage complicating systemic thrombolysis was evaluated using NINDS rtPA Stroke Study definition. Functional outcome at three months was evaluated using the modified Rankin Scale (mRS). Results: Systemic tPA (median onset-to-treatment time 70 min, interquartile range 50-150) was given in 25 consecutive patients (mean age 66±10years) who developed symptoms of acute stroke (median NIHSS-score 10 points; interquartile range 8-14) during hospitalization for prior TIA [(median ABCD2-score 5 points, median time-to-symptom recurrence 24 hrs, interquartile range 24-48). No symptomatic intracranial hemorrhage (0%; 95%CI:0-12%) was documented. Early complete recanalization occurred in 64% (95%CI:44%-80%) of the study population; 84% (95%CI:65%-94%) achieved three-month functional independence (mRS-score of 0-2). The rate of three-month functional independence was higher in patients treated with iv-tPA within 90 min from symptom onset compared to those with onset-to-treatment time&gt;90 min (81% vs 33%; p=0.031) Conclusions: Intravenous thrombolysis for symptoms of ischemic stroke occurring after hospitalization for TIA appears to be safe. These pilot data support re-setting the clock if new symptoms recur shortly after TIA.