rt-PA For Acute Ischemic Stroke Research Articles

Do women benefit more from systemic thrombolysis in acute ischemic stroke? A Serbian experience with thrombolysis in ischemic stroke (SETIS) study

Objective The female sex is associated with increased stroke severity and relatively poor functional recovery. Several studies have demonstrated that women with stroke benefit more from intravenous thrombolysis compared with men, while others found the nullification of gender effect among women treated with recombinant tissue plasminogen activator (rtPA). The purpose of our study was to determine any gender differences in the efficacy and safety of systemic thrombolysis among patients with acute ischemic stroke in Serbia. Methods Data were from the Serbian experience with intravenous thrombolysis in ischemic stroke (SETIS) study, a prospective, ongoing, multicenter, open, and observational study in Serbia of all patients who have received rtPA for acute ischemic stroke. We analyzed sex differences in the baseline characteristics, functional outcome and treatment complications. Results Among 60 women and 96 men with stroke and treated with intravenous thrombolysis, we found that at day 90, no significant sex differences in excellent functional outcome (50.9% of women vs. 57.0% of men, p = 0.5), favorable functional outcome (61.4% of women vs. 68.8% of men, p = 0.38) or death (8.8% of women vs. 12.9% of men, p = 0.60). These results were constant even after adjustments for age, severity of basal neurological deficit and onset to treatment time. Conclusion There were no sex differences in functional outcome at 90 days after the stroke among patients treated with IV rtPA. This finding might confirm that thrombolytic therapy nullifies usual sex differences in stroke outcome and suggests that women with stroke may benefit more from rtPA treatment.

Third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke.

BackgroundIntravenous recombinant tissue plasminogen activator (rt-PA) is approved for use in selected patients with ischaemic stroke within 3 hours of symptom onset. IST-3 seeks to determine whether a wider range of patients may benefit.DesignInternational, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rt-PA in acute ischaemic stroke. Suitable patients must be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracerebral haemorrhage. With 1000 patients, the trial can detect a 7% absolute difference in the primary outcome. With3500 patients, it can detect a 4.0% absolute benefit & with 6000, (mostly treated between 3 & 6 hours), it can detect a 3% benefit.Trial proceduresPatients are entered into the trial by telephoning a fast, secure computerised central randomisation system or via a secure web interface. Repeat brain imaging must be performed at 24–48 hours. The scans are reviewed 'blind' by expert readers. The primary measure of outcome is the proportion of patients alive and independent (Modified Rankin 0–2) at six months (assessed via a postal questionnaire mailed directly to the patient). Secondary outcomes include: events within 7 days (death, recurrent stroke, symptomatic intracranial haemorrhage), outcome at six months (death, functional status, EuroQol).Trial registrationISRCTN25765518

Pre-hospital delay in the use of intravenous rt-PA for acute ischemic stroke in Japan

In this study we investigated the factors associated with pre-hospital delay to treat acute ischemic stroke and transient attack with intravenous recombinant tissue-plasminogen activator (rt-PA) in Japan. In 625 patients, we investigated the pathways and times of their arrival to our hospital, and the significant and independent factors in the patients' clinical backgrounds associated with delayed arrival (>2 h after notice). In total, 287 patients arrived at our hospital directly via EMS, 113 came by themselves, and 225 transferred from other institutes. Delayed arrivals occurred in 423 patients (68%). Multivariate analyses showed that staying in another hospital at notice, a worsened course, and referral from other institutes were positively related, and evening onset, having a witness at onset, loss of consciousness, and using EMS were negatively related to delayed arrival; a worsened course was positively related, and staying in other hospital at notice, having a witness at onset, loss of consciousness, and a high NIHSS on admission were negatively related to delayed alert; hypercholesterolemia and onset in a nursing home were positively related, and staying in other hospital at notice, loss of consciousness, and a high NIHSS on admission were negatively related to not using EMS. A lack of knowledge concerning stroke emergency by medical staff as well as the general public may be responsible for some stroke patients losing the chance for rt-PA treatment.

Telephonic guidance of systemic thrombolysis in acute ischemic stroke: Safety outcome in rural hospitals

Objectives To determine the safety of telephonic guidance for use of intravenous recombinant tissue plasminogen activator (IV rtPA) in rural hospitals. Patients and methods We performed a retrospective survey of 123 consecutive patients treated with IV rtPA for acute ischemic stroke (AIS) in rural hospitals between November 2003 and September 2006 and subsequently transferred to a tertiary medical center. Selection for treatment was performed by a stroke neurologist who conducted a structured telephone interview of the requesting physician. Primary outcome measures included symptomatic intracerebral hemorrhage (ICH) and in-hospital mortality. Results Elapsed time (ET) from stroke onset to community hospital arrival was 54 ± 30 min. ET from stroke onset to tPA bolus was 133 ± 37 min. Three patients (2.5%) had symptomatic ICH, 11 (9%) had asymptomatic ICH, 9 patients (7.5%) died. Mean length of stay was 4 ± 3 days; 47% were discharged to their homes. Mean ET from stroke onset to rtPA dosage did not differ significantly from the active treatment group of the NINDS rtPA Stroke Study. Prevalence of symptomatic ICH and mortality were lower in our population. Conclusion We conclude that telephonic guidance of rtPA treatment is safe, practical, and effective in overcoming barriers for optimal care of AIS in rural communities.

National US Estimates of Recombinant Tissue Plasminogen Activator Use

Current US estimates of recombinant tissue plasminogen activator (rt-PA) use have been based either on extrapolation of regional studies or on administrative database estimates, both of which may have inherent biases. We sought to compare the utilization of rt-PA in acute ischemic stroke in the MEDPAR database to another national hospital database with drug utilization information. Cases were defined as DRG 14,15, and 524 and ICD-9 code 99.1, which indicates cerebral thrombolysis, for fiscal year 2001 to 2004. Additionally, the Premier database was queried for rt-PA utilization documented in pharmacy records in those patients admitted for stroke. Change over time and difference between databases were tested using Poisson regression. When comparing databases, rt-PA use, as identified by ICD-9 code 99.1, was only documented in 0.95% of stroke cases in 2004 in MEDPAR, and 1.2% in the Premier database, which slightly increased by 0.04% to 0.09% over time. Analysis of pharmacy billing records increased the estimate to 1.82%. Exclusion of cases younger than 65 years excluded 43% of cases treated with rt-PA. In 2004, 12.7% of cases receiving thrombolytic had either a TIA or a hemorrhagic stroke ICD-9 code. We estimate the rate of rt-PA use in the United States to be 1.8% to 2.1% of ischemic stroke patients. The rate of thrombolytic use for ischemic stroke was slightly increasing between 2001 and 2004 at a rate of 0.04% to 0.09% per year. A significant proportion of patients treated with rt-PA are likely miscoded as either TIA or hemorrhagic stroke. We conservatively estimate that 10,800 to 12,600 patients received rt-PA in 2004.

Hyperacute thrombolysis with recombinant tissue plasminogen activator of acute ischemic stroke: Feasibility and effectivity from an Indian perspective

Given the constraints of resources, thrombolysis for acute ischemic stroke (AIS) is under evaluation in developing countries like India, especially in areas such as western Utter Pradesh, where it is overly crowded and there is poor affordability.Aim:This study was done to evaluate recombinant tissue plasminogen activator r-tpa in acute ischemic stroke in hyper acute phase, in selected patients of western Utter Pradesh, in terms of feasibility and effectivity.Design:Open, non randomized study.Materials and Methods:Thirty two patients were classified using Trial of ORG 10172 in Acute Stroke treatment (TOAST) criteria (large artery atherosclerotic = 8; cardio embolic = 6; small vessel occlusion = 14; other determined etiology = 2; undetermined etiology = 2). The mean time to reach the hospital was 2 h (1.15-3.0), the mean door to CT scan 20 min (10-40) and door to r-tpa injection was 30 min (24-68). The National Institute of Health Stroke Scale (NIHSS) scores ranged from 11-22 (mean 15.5 +2.7). The dose of r-tpa administered was 0.9 mg/kg.Results:Twenty one patients (65.6%) showed significant improvement on the NIHSS score, at 48 h (4 points). (Mean change = 10; range = 4-17). At one month, 25 (78%) recorded improvement on the Barthel index (mean change = 45%). One developed frontal lobe hemorrhage and another developed recurrent stroke; one died of aspiration; and four showed no improvement. Modified Rankin score (m RS) was administered at the end of three months to 28 patients (90%); however, the rest could not be directly observed. The average modified Rankin Score was 1.2 (0-2).Conclusions:Hyperacute thrombolysis was found feasible and effective in selected patients with AIS from western Utter Pradesh and who had poor affordability.

Thrombolysis with rt-PA in acute ischemic stroke; its light and shadow

Thrombolysis with rt-PA in acute ischemic stroke; its light and shadow

ｒｔ‐ＰＡの使用経験と今後の展望―脳神経外科医の立場から―

Intravenous rt-PA for acute ischemic stroke could be widely accepted as the only treatment which efficacy was proved by well-controlled clinical trials. Based on this clinical evidence, it could be major target for clinical trial how to expand the efficacy of thrombolytic therapy for acute ischemic stroke. Intra-arterial local fibrinolytic intervention which is not necessarily alternative treatment for intravenous rt-PA could be additional treatment for intravenous rt-PA which fails to achieve reopening of occluded vessels within therapeutic time window. Concerning on thrombolytic therapy using intravenous rt-PA, efficacy of newly developed rt-PA which might have wider therapeutic time window should be verified by randomized controlled trials. In addition to that, the combination therapy using intravenous rt-PA and brain protective agents such as free radical scavengers also should be inspected to show improvement of patients outcome or expansion of therapeutic time window.Approval of intravenous rt-PA for acute ischemic stroke in this country make a chance to discuss about local medical care system for acute stroke patients should be, and make a progress to establish primary or comprehensive stroke centers in all over the country.

The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke (the Clear Stroke Trial): Blinded Results from the First Dose Tier

The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke (the Clear Stroke Trial): Blinded Results from the First Dose Tier

Sex-Based Differences in Response to Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke

Women experience worse outcomes after stroke compared with men. Prior work has suggested sex-based differences in coagulation and fibrinolysis markers in subjects with acute stroke. We explored whether sex might modify the effect of recombinant tissue plasminogen activator (rtPA) on outcomes in patients with acute ischemic stroke. Using a combined database including subjects from the National Institute of Neurological Disorders and Stroke (NINDS), Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) A and B, and the Second European Cooperative Acute Stroke Study (ECASS II) trials, we examined 90-day outcomes in patients randomized to rtPA versus placebo by sex. We used logistic regression to control for potential confounders. Among 988 women treated between 0 and 6 hours from symptom onset, patients receiving rtPA were significantly more likely than those receiving placebo to have a modified Rankin Score < or =1 (40.5% versus 30.3%, P<0.0008). Among 1190 men, the trend toward benefit in the overall group did not reach statistical significance (38.5% versus 36.7%, P=0.52). An unadjusted analysis showed that women were significantly more likely to benefit from rtPA compared with men (P=0.04). Controlling for age, baseline National Institutes of Health Stroke Scale, diabetes, symptom onset to treatment time, prior stroke, systolic blood pressure, extent of hypoattenuation on baseline computed tomography scan and several significant interaction terms (including onset to treatment time-by-treatment and systolic blood pressure-by treatment) did not substantially change the strength of the interaction between gender and rtPA treatment (P=0.04). In this pooled analysis of rtPA in acute ischemic stroke, women benefited more than men, and the usual gender difference in outcome favoring men was not observed in the thrombolytic therapy group. For patients presenting at later time intervals, when the risks and benefits of rtPA are more finely balanced, sex may be an important variable to consider for patient selection.

Influence of pretreatment MRI parameters on clinical outcome, recanalization and infarct size in 49 stroke patients treated by intravenous tissue plasminogen activator

We hypothesized that pretreatment magnetic resonance imaging (MRI) parameters might predict clinical outcome, recanalization and final infarct size in acute ischemic stroke patients treated by intravenous recombinant tissue plasminogen activator (rt-PA). MRI was performed prior to thrombolysis and at day 1 with the following sequences: magnetic resonance angiography (MRA), T2*-gradient echo (GE) imaging, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). Final infarct size was assessed at day 60 by T2-weighted imaging (T2-WI). The National Institutes of Health Stroke Scale (NIHSS) score was assessed prior to rt-PA therapy and the modified Rankin Scale (m-RS) score was assessed at day 60. A poor outcome was defined as a day 60 m-RS score >2. Univariate and multivariate logistic regression analyses were used to identify the predictors of clinical outcome, recanalization and infarct size. Forty-nine patients fulfilled the inclusion criteria. Baseline NIHSS score was the best independent indicator of clinical outcome ( p=0.002). A worse clinical outcome was observed in patients with tandem internal carotid artery (ICA)+middle cerebral artery (MCA) occlusion versus other sites of arterial occlusion ( p=0.009), and in patients with larger pretreatment PWI ( p=0.001) and DWI ( p=0.01) lesion volumes. Two factors predict a low rate of recanalization: a proximal site of arterial occlusion ( p=0.02) and a delayed time to peak (TTP) on pretreatment PWI ( p=0.05). The final infarct size was correlated with pretreatment DWI lesion volume ( p=0.025). Recanalization was associated with a lower final infarct size ( p=0.003). In conclusion, a severe baseline NIHSS score, a critical level of pretreatment DWI/PWI parameters and a proximal site of occlusion are predictive of a worse outcome after IV rt-PA for acute ischemic stroke.

Enhancement of enzymatic fibrinolysis with 2‐MHz ultrasound and microbubbles

Microbubbles used for echo-contrast agents accelerate enzymatic fibrinolysis of clots exposed to low-frequency ultrasound (US). It is not known whether microbubbles are also effective in enhancing high-frequency US-driven enzymatic fibrinolysis. Calibrated whole blood clots were exposed to US, or US and galactose-based microbubbles (Levovist), with or without recombinant tissue plasminogen activator (rt-PA) in an in-vitro flow system. We used low-intensity, 2-MHz, pulsed wave US. Relative weight reduction of clot +/- SD was 30.7 +/- 9.5% after exposure to microbubbles, rt-PA and US, 13.1 +/- 2.6% after exposure to rt-PA and US, 10.9 +/- 3.6% after exposure to microbubbles and US, and 6.1 +/- 1.9% after exposure to US alone. anova demonstrated a significant effect of rt-PA (P =0.001), microbubbles (P = 0.012), and interaction of both (P = 0.022). The application of galactose-based microbubbles (Levovist) strongly accelerates lysis of clots exposed to 2 MHz, low-intensity US in vitro both with and without rt-PA. The findings suggest a synergy between microbubbles and rt-PA. These methods routinely used for transcranial diagnostic applications have the potential to improve the efficacy of intravenous rt-PA in acute ischemic stroke.

Thrombolytic therapy with recombinant tissue plasminogen activator for acute ischemic stroke: where do we go from here? A cumulative meta-analysis.

Recombinant tissue plasminogen activator (rtPA; Actilyse) is not as widely used in clinical practice as it could be. Have new data since 1995 strengthened the evidence sufficiently to justify more widespread use of rtPA? We performed a sequential year-to-year cumulative meta-analysis of randomized controlled trials of rtPA in acute ischemic stroke. Although the amount of data has doubled since 1995, effect estimates for key outcomes remain imprecise, and significant between-trial heterogeneity persists. In the most recent analysis, rtPA up to 6 hours after stroke yielded 55 fewer dead or dependent people per 1000 treated (95% CI, 18 to 92) despite some risk (nonsignificant excess of 19 deaths per 1000 patients treated; 95% CI, 6 fewer to 48 more). Severity of stroke, patient age, and aspirin use were possible sources of heterogeneity. Despite doubling of the data since 1995, the magnitude of risks and benefits with rtPA remains imprecise. This gap in knowledge may be hindering clinical use of rtPA and can be filled only by new trials designed to address these specific issues.

Traitement thrombolytique de lˈaccident ischémique cérébral

The efficacy of thrombolytic therapy of acute ischemic stroke has recently been assessed by several clinical trials. Results suggest that intravenous rt-PA benefits carefully selected patients despite an increased risk of severe hemorrhagic transformation. This therapy should be used only by experienced physicians. Intravenous rt-PA for acute ischemic stroke has not yet been approved by European regulatory authorities.

Stroke in the developing world

Stroke is the third most common cause of death in most western populations after coronary-heart disease and cancer? It is thus the commonest life-threatening neurological disorder, and the resulting disability is the most important single cause of severe disability among western people living in their own homes) The burden of stroke on patients, their families, and society is, correctly, publicised in most developed countries. Stroke in the developing world is less well documented, and some data are not retrievable because of the language barrier or the limited dissemination of data collected. However, more than two-thirds of the world's population live in developing countries, and one of the consensus statements from the Asia-Pacific Consensus Forum on Stroke Management predicts that "In the next 30 years the burden of stroke will grow most in developing countries rather than in developed countries"? Thus stroke in developing countries ought to be examined further--in particular, the similarities and differences in stroke between developed and developing countries.

Neurologists' attitudes regarding rt-PA for acute ischemic stroke.

We studied the attitudes of 238 Texas neurologists regarding the use of recombinant tissue plasminogen activator (rt-PA). The results show that 38 (16%) had treated stroke patients with rt-PA, and 97% of these would do so again. In the group that had not treated patients, 60% would treat if a suitable candidate presented. We conclude that soon after FDA approval of rt-PA, two-thirds of survey respondents were using or were planning to use this therapy. Those neurologists who have used rt-PA for stroke report a positive experience.

Nursing management of acute complications following rt-PA in acute ischemic stroke. The NINDS rt-PA Stroke Study Group.

In the National Institutes of Neurologic Disorders and Stroke (NINDS) recombinant tissue plasminogen activator (rt-PA) stroke trial, the primary adverse events monitored were intracranial hemorrhage (ICH), systemic bleeding, death and new stroke. Nurses caring for the study patients noted these adverse events and other complications. In addition to what is known about acute ischemic stroke (AIS), the NINDS trial provides further information for optimal care of this specific group of patients. The complications found in this trial require expert nursing care to monitor, prevent and intervene, making clinical decisions relevant to the patients needs. The critical decision-making process must be grounded in knowledge of acute stroke physiology and thrombolysis.

RtPA in acute ischemic stroke: the North American perspective.

Pilot studies with recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke suggested that early clot lysis can be performed with acceptable safety. If thrombolytic recanalization of occluded arteries can be performed before the infarction process has been completed, it may reduce the degree of ischemic injury to the brain. The North American perspective on thrombolytic therapy with rtPA in acute ischemic stroke is derived largely from these early pilot studies and the results of the phase III trial conducted by the National Institute of Neurological Disorders and Stroke(NINDS) rtPA Stroke Study group.1 On the basis of the NINDS study results, in mid-1996 the US Food and Drug Administration (FDA) advisory committee voted unanimously to recommend approval. The FDA approval followed rapidly for treatment of patients within 3 hours after onset of acute ischemic stroke. This article reviews the design and results of that study and its impact on current attitudes toward the management of patients with acute ischemic stroke in North America. NINDS trial design. The NINDS trial was a phase III, multicenter, randomized, placebo-controlled, double-blind study conducted in eight centers in the United States. It was divided into two parts and enrolled a total of 624 patients in the combined study. The first part of the study was designed to assess whether patients receiving rtPA achieved significant early improvement in neurologic deficits compared to those receiving placebo. Early improvement was defined as complete resolution of the neurologic deficit or an improvement from baseline of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) 24 hours after the onset of stroke. The second, pivotal part of the NINDS trial was an outcomes study that assessed whether treatment with rtPA reduced the chance of disability in those receiving rtPA compared with those receiving placebo measured …

Asymmetric Angioneurotic Edema Associated With Thrombolysis for Acute Stroke

We present a case of acute asymmetric angioneurotic edema associated with the use of recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke. rtPA was administered for an acute ischemic stroke in accordance with the recently reported National Institute of Neurological Disorders and Stroke protocol, after which marked asymmetric angioedema requiring upper-airway control developed. Although atypical and anaphylactoid reactions have been reported with the use of rtPA for acute myocardial infarction, to our knowledge this is the first case report of asymmetric angioedema associated with the use of rtPA for acute ischemic stroke. [Pancioli A, Brott T, Donaldson V, Miller R: Asymmetric angioneurotic edema associated with thrombolysis for acute stroke. Ann Emerg Med August 1997;30:227-229.]