Alteplase In Patients Research Articles

Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial

Tenecteplase is a newer thrombolytic agent with some pharmacological advantages over alteplase. Previous phase 2 trials of tenecteplase in acute ischaemic stroke have shown promising results. We aimed to investigate the safety and efficacy of tenecteplase versus alteplase in patients with acute stroke who were eligible for intravenous thrombolysis. This phase 3, randomised, open-label, blinded endpoint, superiority trial was done in 13 stroke units in Norway. We enrolled adults with suspected acute ischaemic stroke who were eligible for thrombolysis and admitted within 4·5 h of symptom onset or within 4·5 h of awakening with symptoms, or who were eligible for bridging therapy before thrombectomy. Patients were randomly assigned (1:1) to receive intravenous tenecteplase 0·4 mg/kg (to a maximum of 40 mg) or alteplase 0·9 mg/kg (to a maximum of 90 mg), via a block randomisation schedule stratified by centre of inclusion. Patients were not informed of treatment allocation; treating physicians were aware of treatment allocation but those assessing the primary and secondary endpoints were not. The primary outcome was excellent functional outcome defined as modified Rankin Scale (mRS) score 0-1 at 3 months. The primary analysis was an unadjusted and non-stratified intention-to-treat analysis with last observation carried forward for imputation of missing data. This study is registered with ClinicalTrials.gov, number NCT01949948. Between Sept 1, 2012, and Sept 30, 2016, 1107 patients met the inclusion criteria and seven patients were excluded because informed consent was withdrawn or eligibility for thrombolytic treatment was reconsidered. 1100 patients were randomly assigned to the tenecteplase (n=549) or alteplase (n=551) groups. The median age of participants was 77 years (IQR 64-79) and the median National Institutes of Health Stroke Scale score at baseline was 4 points (IQR 2-8). A final diagnosis other than ischaemic stroke or transient ischaemic attack was found in 99 (18%) patients in the tenecteplase group and 91 (17%) patients in the alteplase group. The primary outcome was achieved by 354 (64%) patients in the tenecteplase group and 345 (63%) patients in the alteplase group (odds ratio 1·08, 95% CI 0·84-1·38; p=0·52). By 3 months, 29 (5%) patients had died in the tenecteplase group compared with 26 (5%) in the alteplase group. The frequency of serious adverse events was similar between groups (145 [26%] in the tenecteplase group vs 141 [26%] in the alteplase group; p=0·74). Tenecteplase was not superior to alteplase and showed a similar safety profile. Most patients enrolled in this study had mild stroke. Further trials are needed to establish the safety and efficacy in patients with severe stroke and whether tenecteplase is non-inferior to alteplase. Research Council of Norway.

CLINICAL RESULTS OF THROMBOLYTIC THERAPY WITH ALTEPLASE AND TENECTEPLASE IN PATIENTS WITH MYOCARDIAL INFARCTION

CLINICAL RESULTS OF THROMBOLYTIC THERAPY WITH ALTEPLASE AND TENECTEPLASE IN PATIENTS WITH MYOCARDIAL INFARCTION

Coagulation and Fibrinolytic Activity of Tenecteplase and Alteplase in Acute Ischemic Stroke.

We compared the fibrinolytic activity of tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and intracerebral hemorrhage. Venous blood samples from a subgroup of participants in the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study were obtained at pretreatment, 3 to 12 hours, and 24±3 hours post-intravenous thrombolysis for analyses of plasminogen, plasminogen activator inhibitor-1, d-dimer, factor V, fibrinogen, and fibrin(ogen) degradation products, in addition to routine coagulation assays. Related sample Wilcoxon signed-rank tests were used to test the within-group changes, and independent Mann-Whitney tests for between-group differences. Thirty patients were included (alteplase=14 and tenecteplase=16) with similar baseline demographics. Compared with baseline, alteplase caused significant hypofibrinogenaemia (P=0.002), prolonged prothrombin time (P=0.011), hypoplasminogenaemia (P=0.001), and lower factor V (P=0.002) at 3 to 12 hours after administration with persistent hypofibrinogenaemia at 24 hours (P=0.011), whereas only minor hypoplasminogenaemia (P=0.029) was seen in the tenecteplase group. Tenecteplase consumed less plasminogen (P<0.001) and fibrinogen (P=0.002) compared with alteplase. In patients with acute ischemic stroke, alteplase 0.9 mg/kg caused significant disruption of the fibrinolytic system, whereas tenecteplase 0.25 mg/kg did not, consistent with the trend toward lower intracerebral hemorrhage incidence with tenecteplase in the ATTEST study. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472926.

Remote Ischemic Perconditioning as an Adjunct Therapy to Thrombolysis in Patients With Acute Ischemic Stroke

Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia. We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke. Open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke. After neurological examination and MRI, patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months. The primary end point was penumbral salvage, defined as the volume of the perfusion-diffusion mismatch not progressing to infarction after 1 month. Four hundred forty-three patients were randomized after provisional consent, 247 received rPerC and 196 received standard treatment. Patients with a nonstroke diagnosis (n=105) were excluded from further examinations. The remaining patients had transient ischemic attack (n=58), acute ischemic stroke (n=240), or hemorrhagic stroke (n=37). Transient ischemic attack was more frequent (P=0.006), and National Institutes of Health Stroke Scale score on admission was lower (P=0.016) in the intervention group compared with controls. Penumbral salvage, final infarct size at 1 month, infarct growth between baseline and 1 month, and clinical outcome after 3 months did not differ among groups. After adjustment for baseline perfusion and diffusion lesion severity, voxelwise analysis showed that rPerC reduced tissue risk of infarction (P=0.0003). Although the overall results were neutral, a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects. Future clinical trials should take such immediate effects, and their duration, into account. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00975962.

Increased Benefit of Alteplase in Patients with Ischemic Stroke and a High Body Temperature

Background: In observational studies, a high body temperature has been associated with unfavorable outcome. In in vitro studies, the fibrinolytic activity of alteplase decreased 5% per degree Celsius reduction in temperature. The modifying effect of body temperature on treatment with alteplase in patients with acute ischemic stroke is unclear. We assessed the influence of baseline body temperature on the effect of alteplase on functional outcome in patients with acute ischemic stroke, included in the Paracetamol (Acetaminophen) in Stroke (PAIS) trial. Methods: PAIS was a randomized, double-blind clinical trial to assess the effect of high-dose paracetamol on functional outcome in patients with acute stroke. For this study, we selected all patients with ischemic stroke and randomization within 6 h of symptom onset. We estimated the effect of treatment with alteplase on the modified Rankin Scale score at 3 months with ordinal logistic regression, stratified by baseline body temperature. We made adjustments for confounding factors and expressed associations as adjusted odds ratios (aOR) with 95% confidence intervals (CI). We also tested for interaction between treatment with alteplase and body temperature. Results: We included 647 of the 1,400 patients in PAIS in our study. Treatment with alteplase was associated with improved functional outcome at 3 months (aOR 1.51, 95% CI 1.09–2.08). In the 286 patients (44%) with a baseline body temperature of 37.0°C or higher, alteplase was associated with a larger effect (aOR 2.13, 95% CI 1.28–3.45) than in patients with a temperature below 37.0°C (aOR 1.11, 95% CI 0.71–1.69). A test for interaction between body temperature and alteplase did not reach statistical significance (p = 0.18). Conclusion: Patients with ischemic stroke and a high body temperature may have a larger benefit of treatment with alteplase than patients with lower body temperatures. These findings are in line with those from in vitro studies, in which lowering temperature decreased the fibrinolytic activity of the enzyme alteplase. This interaction should be explored further in randomized clinical trials of thrombolytic therapy or modification of body temperature. Trials of therapeutic hypothermia should be controlled for treatment with thrombolytics, and trials of thrombolytic treatment should consider body temperature as a potential effect modifier.

The efficacy and safety of intravenous thrombolysis with alteplase in the treatment of ischaemic stroke in a rural hospital

Background and purposeOngoing evaluation of the results of thrombolytic therapy in patients with ischaemic stroke (IS) in regions with different health care organization is absolutely crucial for making this method of treatment safer and efficient. The aim of this study was to analyse the efficacy and safety of treatment with intravenous alteplase in patients with acute IS in a rural hospital. Material and methodsBetween 2006 and 2011, 1392 patients with IS were treated (including 200 patients treated with alteplase; 14.37%). In patients treated with alteplase, we analysed the influence of several variables on the functional status after 3 months according to the modified Rankin Scale (mRS), case-fatality rate during 3 months after onset and symptomatic intracerebral haemorrhage (SICH). ResultsIn the studied population, good outcome (mRS 0–2) at 3 months was related to younger age (p = 0.001), male sex (p = 0.02) and low scores (< 15 points) on the National Institutes of Health Stroke Scale (NIHSS) (p < 0.0001). Deaths within 3 months were related to older age (p = 0.027), female sex (p = 0.004), severity of stroke measured by NIHSS score (p < 0.0001) and presence of radiological signs of previous stroke in baseline computed tomography (CT) (p = 0.002). Patients with SICH had higher mean age (p = 0.014) and higher severity of neurological deficit measured on the NIHSS scale (p = 0.03). ConclusionsThe indications for intravenous thrombolysis in patients with IS should be strictly analysed so that the treatment is effective and safe especially in older patients, patients with greater severity of neurological symptoms and patients with old post-stroke lesions in baseline CT.

Circadian Rhythms in the Efficacy of Intravenous Alteplase in Patients With Acute Ischemic Stroke and Middle Cerebral Artery Occlusion

Circadian rhythm interactions of hemostatic factors can modify tissue plasminogen activator (tPA) effects. We assess the relationship of the time frame of intravenous tPA administration with the outcome of patients with acute ischemic stroke (AIS). We studied 135 consecutive patients with AIS and transcranial duplex documented middle cerebral artery (MCA) occlusion treated with intravenous tPA. Complete recanalization was defined as total improvement on thrombolysis in brain ischemia (TIBI) grades 2 h after tPA infusion. Clinical response was evaluated by the modified Rankin scale at 90 days. We determined plasminogen activator inhibitor-1 (PAI-1) levels in 33 patients with available plasma samples before treatment. Our results are follows: 92 (68.1%) patients were treated in the diurnal (9:00–21:00) and 43 (31.8%) in the nocturnal period (21:00–9:00). Complete recanalization was recorded in 52/135 (38.5%) patients. Both the rate of complete recanalization (45.6% vs. 23.2%; p = .01) and good clinical outcome (64.1% vs. 44.2%; p = .02) were significantly higher in the group of diurnal tPA administration compared with those treated in the nocturnal period. The adjusted odds ratio (OR) of diurnal tPA treatment for complete MCA recanalization was 2.37 (95% confidence interval [CI], 1.02–5.52; p = .045). Diurnal tPA infusion significantly improved the overall distribution of scores on the modified Rankin scale, as compared with nocturnal treatment (OR, 2.07; 95% CI, 1.16–4.64 by ordinal regression analysis). Low PAI-1 levels were associated with complete recanalization but did not significantly differ between the two time frames. In conclusion, diurnal administration of tPA is associated with complete MCA recanalization and better functional outcome at 90 days in patients with AIS. (Author correspondence: mgomis.germanstrias@gencat.cat, meritxellgomis@gmail.com)

289 The use of alteplase in patients’ portacaths following transfer from paediatric to the adult unit

289 The use of alteplase in patients’ portacaths following transfer from paediatric to the adult unit

A Randomized Trial of Tenecteplase versus Alteplase for Acute Ischemic Stroke

BackgroundIntravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, is an alternative thrombolytic agent.MethodsIn this phase 2B trial, we randomly assigned 75 patients to receive alteplase (0.9 mg per kilogram of body weight) or tenecteplase (0.1 mg per kilogram or 0.25 mg per kilogram) less than 6 hours after the onset of ischemic stroke. To favor the selection of patients most likely to benefit from thrombolytic therapy, the eligibility criteria were a perfusion lesion at least 20% greater than the infarct core on computed tomographic (CT) perfusion imaging at baseline and an associated vessel occlusion on CT angiography. The coprimary end points were the proportion of the perfusion lesion that was reperfused at 24 hours on perfusion-weighted magnetic resonance imaging and the extent of clinical improvement at 24 hours as assessed on the National Institutes of Health Stroke Scale (NIHSS, a 42-point scale on which higher scores indicate more severe neurologic deficits).ResultsThe three treatment groups each comprised 25 patients. The mean (±SD) NIHSS score at baseline for all patients was 14.4±2.6, and the time to treatment was 2.9±0.8 hours. Together, the two tenecteplase groups had greater reperfusion (P=0.004) and clinical improvement (P<0.001) at 24 hours than the alteplase group. There were no significant between-group differences in intracranial bleeding or other serious adverse events. The higher dose of tenecteplase (0.25 mg per kilogram) was superior to the lower dose and to alteplase for all efficacy outcomes, including absence of serious disability at 90 days (in 72% of patients, vs. 40% with alteplase; P=0.02).ConclusionsTenecteplase was associated with significantly better reperfusion and clinical outcomes than alteplase in patients with stroke who were selected on the basis of CT perfusion imaging. (Funded by the Australian National Health and Medical Research Council; Australia New Zealand Clinical Trials Registry number, ACTRN12608000466347.)

Intravenous Alteplase in Ischemic Stroke Patients not Fully Adhering to the Current Drug License in Central and Eastern Europe

The current European license for alteplase in acute ischemic stroke excludes from treatment large groups of patients. Nevertheless, in everyday practice, many patients receive off-label thrombolysis at the physician's discretion. Our aim was to evaluate safety and effectiveness of intravenous alteplase in patients not fully adhering to the drug license compared with those treated strictly according to the license in Central and Eastern Europe. We analyzed the data contributed to Safe Implementation of Thrombolysis in Stroke registry from nine countries between February 2003 and February 2010. Statistical analysis included multivariate logistic regression. Of 5594 consecutive patients, 1919 patients (34·3%) not fully adhered to the license. The most frequent deviations were: time-to-treatment >3 h (13·1%), use of intravenous antihypertensives (8·3%), age >80 years (7·3%), oral anticoagulation (4·2%), a previous stroke with concomitant diabetes (3·9%), and previous stroke <three-months (2·7%). The off-label group showed a significantly higher rate of symptomatic intracranial haemorrhage, which was not confirmed in the multivariate analysis. License nonadherence significantly increased the risk of death or dependency (odds ratio 1·26; 95% confidence interval: 1·08-1·48), with a trend for increased mortality (odds ratio 1·17; 95% confidence interval: 0·97-1·42). Isolated time-to-treatment >3 h was an independent predictor of unfavorable outcome (odds ratio 1·32; 95% confidence interval: 1·01-1·71). Our findings show that patients not fully adhering to the European license are not at increased risk of symptomatic intracranial haemorrhage but achieve less favorable outcome. Some contraindications appear more redundant than others. However, the final conclusions about safety and effectiveness should be based on the results of ongoing randomized trials.

CLINICAL RESULTS OF THROMBOLYTIC THERAPY WITH ALTEPLASE AND TENECTEPLASE IN PATIENTS WITH MYOCARDIAL INFARCTION

Aim. To evaluate the clinical results of thrombolytic therapy with thrombolytics (alteplase, tenecteplase) in patients with ST segment elevation myocardial infarction (STEMI). Material and methods. Patients with STEMI (n=181) included in the study were split into two groups depending on the thrombolytic agent: patients treated with alteplase - group 1 (n=78); patients treated with tenecteplase — group 2 (n=52). Patients with STEMI who had no thrombolysis due to late treatment-seeking or the presence of contraindications were included into the group 3 (n=51). Thrombolysis took place both in pre-hospital and in-hospital period. Time before the thrombolysis, STEMI clinical course, mortality , and complications were analyzed. Results. The average time pain-thrombolysis was 2.7±0.22 hours. High efficacy of both thrombolytic drugs was proved in the most of patients. Mortality in patients received thrombolysis was 6.4–7.7%; this in patients without thrombolytic therapy — 24%. Thrombolysis performed in the first 3 hours after STEMI onset reduced mortality to 3.4%. No one intracranial hemorrhage or allergic reaction was registered. Conclusion. Thrombolytic therapy with alteplase and tenecteplase in patients with STEMI in the real clinical practice was high efficient, reduced hospital mortality and induced a few adverse reactions.

Clinical effectiveness of thrombolytic therapy with alteplase and double antiplatelet therapy in acute myocardial infarction

Aim. To assess the clinical effectiveness of thrombolytic therapy (TLT) with alteplase in patients with acute myocardial infarction (AMI). Material and methods. The study included 54 AMI patients, divided into two groups: Group I (n=26), which underwent TLT, and Group II (n=28), which had contraindications to TLT. The TLT method was an accelerated alteplase infusion. Both groups were comparable by age and sex. In all patients, AMI biomarker levels and echocardiography (EchoCG) parameters were measured. Results. Successful thrombolysis was performed in 19 patients (73 %). The mean “symptom-to-needle” time was 3,7±0,6 hours. In Groups I and II, the 50 % reduction in the ST segment deviation from isoelectric line at 180 minutes was observed in 34,6 % and 0 % of the patients, respectively. In addition, in Group I, there was a reduction in the number of patients complaining of general weakness, dyspnoea, and recurrent angina attacks. The levels of cardio-specific AMI biomarkers were higher in Group II. According to the EchoCG results at 10 days after admission, the Group I patients demonstrated higher minute volume (by 28,8 %), higher ejection fraction (by 30 %), and higher end-diastolic dimension (by 23,8 %). Conclusion. The results obtained confirm high effectiveness of the in-hospital TLT with accelerated alteplase infusion. Alteplase therapy was associated with clinical and morphological myocardial salvage in AMI patients.

Residual Vessel Length on Magnetic Resonance Angiography Identifies Poor Responders to Alteplase in Acute Middle Cerebral Artery Occlusion Patients

It remains unknown whether the effects of 0.6 mg/kg alteplase differ with occlusion site of the middle cerebral artery (MCA). We therefore evaluated the effects of 0.6 mg/kg intravenous alteplase in patients with different sites of MCA occlusion. An exploratory analysis was made of 57 patients enrolled in the Japan Alteplase Clinical Trial II (J-ACT II), originally designed to evaluate 0.6 mg/kg alteplase in Japanese patients with unilateral occlusion of the MCA (M1 or M2 portion). The residual vessel length (in mm), determined by pretreatment magnetic resonance angiography, was used to reflect the occluded site. The proportions of patients with valid recanalization (modified Mori grade 2 to 3) at 6 and 24 hours and a modified Rankin Scale (mRS) score of 0 to 1 and of 0 to 2 at 3 months were compared between the groups dichotomized according to length of the residual vessel. Multiple logistic-regression models were generated to elucidate the predictors of valid recanalization, mRS 0 to 1, and mRS 0 to 2. Receiver operating characteristics analysis revealed that 5 mm was the practical cutoff length for dichotomization. In patients with an M1 length < 5 mm (n = 12), the frequencies of valid recanalization at 6 and 24 hours (16.7% and 25.0%) were significantly lower compared with those (62.1% and 82.8%, respectively) of the 45 patients with a residual M1 length ≥ 5 mm and an M2 occlusion (P = 0.008 for 6 hours, P < 0.001 for 24 hours). The proportions of patients who achieved an mRS of 0 to 1 and an mRS of 0 to 2 were also lower for those with an M1 length < 5 mm (8.3% and 16.7%, respectively) compared with the other group (57.8% and 68.9%, respectively; P = 0.003 for mRS 0 to 1, P = 0.002 for mRS 0 to 2). In logistic-regression models, the site of MCA occlusion (< 5 mm) was a significant predictor of valid recanalization at 6 and 24 hours and of an mRS of 0 to 1 and of mRS of 0 to 2. In patients with acute MCA occlusion, a residual vessel length < 5 mm on magnetic resonance angiography can identify poor responders to 0.6 mg/kg alteplase. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412867.

Comparison of Outcomes Following Thrombolytic Therapy Among Patients With Prior Stroke and Diabetes in the Virtual International Stroke Trials Archive (VISTA)

OBJECTIVEThe use of alteplase in patients who have had a prior stroke and concomitant diabetes is not approved in Europe. To examine the influence of diabetes and prior stroke on outcomes, we compared data on thrombolysed patients with nonthrombolysed comparators.RESEARCH DESIGN AND METHODSWe selected patients with ischemic stroke on whom we had data on age, pretreatment baseline National Institutes of Health Stroke Scale (b-NIHSS), and 90-day outcome measures (functional modified Rankin score [mRS]) and neurological measures [NIHSS]) in the Virtual International Stroke Trials Archive. We compared outcomes between thrombolysed patients and nonthrombolysed comparators in those with and without diabetes, those who have had a prior stroke, or both and report findings using the Cochran-Mantel-Haenszel (CMH) test and proportional odds logistic regression analyses. We report an age-adjusted and b-NIHSS–adjusted CMH P value and odds ratio (OR).RESULTSRankin data were available for 5,817 patients: 1,585 thrombolysed patients and 4,232 nonthrombolysed comparators. A total 1,334 (24.1%) patients had diabetes, 1,898 (33.7%) patients have had a prior stroke, and 491 (8%) patients had both. Diabetes and nondiabetes had equal b-NIHSS (median 13; P = 0.3), but patients who have had a prior stroke had higher b-NIHSS than patients who have not had a prior stroke (median 13 vs. 12; P < 0.0001). Functional outcomes were better for thrombolysed patients versus nonthrombolysed comparators among both nondiabetic (P < 0.0001; OR 1.4 [95% CI 1.3–1.6]) and diabetic (P = 0.1; 1.3 [1.05–1.6 ]) subjects. Similarly, outcomes were better for thrombolysed patients versus nonthrombolysed comparators among who have not had a prior stroke (P < 0.0001; 1.4 [1.2–1.6 ]) and those who have (P = 0.02; 1.3 [1.04–1.6 ]). There was no interaction of diabetes and prior stroke with treatment (P = 0.8). Neurological outcomes were consistent with the mRS.CONCLUSIONSOutcomes from thrombolysis are better among patients with diabetes and/or those who have had a prior stroke than in control subjects. Withholding thrombolytic treatment from otherwise-eligible patients may not be justified.

Comparison of intravenous alteplase with a combined intravenous–endovascular approach in patients with stroke and confirmed arterial occlusion (RECANALISE study): a prospective cohort study

The efficacy of intravenous (IV) alteplase is restricted by the speed of recanalisation and the site of the occlusion. The aim of this study was to ascertain the effect of a combined IV-endovascular approach (intra-arterial alteplase and, if required, additional thrombectomy) in patients with stroke due to arterial occlusion. We compared recanalisation rates, neurological improvement at 24 h, and functional outcome at 3 months between two periods (February, 2002, to March, 2007, vs April, 2007, to October, 2008) in patients in a prospective registry who were treated with different regimens of alteplase within 3 h of symptom onset. Patients with confirmed occlusion who were treated before April, 2007, were treated with IV alteplase; after April, 2007, patients were treated with a systematic IV-endovascular approach. Analysis was by intention to treat. 46 (87%) of 53 patients treated with the IV-endovascular approach achieved recanalisation versus 56 (52%) of 107 patients in the IV group (adjusted relative risk [RR] 1.49, 95% CI 1.21-1.84; p=0.0002). Early neurological improvement (NIHSS score of 0 or 1 or an improvement of 4 points or more at 24 h) occurred in 32 (60%) patients in the IV-endovascular group and 42 (39%) patients in the IV group (adjusted RR 1.36, 0.97-1.91; p=0.07). Favourable outcome (mRS of 0-2 at 90 days) occurred in 30 (57%) patients in the IV-endovascular group and 47 (44%) patients in the IV group (adjusted RR 1.16, 0.85-1.58; p=0.35). The mortality rate at 90 days was 17% in both groups, and symptomatic intracranial haemorrhage was reported in five (9%) patients in the IV-endovascular group and in 12 (11%) patients in the IV group. Better clinical outcome was associated with recanalisation in both groups and with time to recanalisation in the IV-endovascular group. An IV-endovascular approach is associated with higher recanalisation rates than is IV alteplase in patients with stroke and confirmed arterial occlusion. In patients treated with an IV-endovascular approach, a shorter time from symptom onset to recanalisation is associated with better clinical outcomes.

The Therapeutic Efficacy and the Bleeding Complications of Urokinase and Alteplase in Patients with Massive Pulmonary Thromboembolism

Background: The efficacy of several thrombolytic agents for treating massive pulmonary thromboembolism (PTE) has been reported to be similar. However, the difference of the bleeding complications caused by two commonly used thrombolytic agents in PTE patients is not well known. The aim of this study was to compare the therapeutic efficacy and the bleeding complications between urokinase and recombinant tissue-type plasminogen activatior (rt-PA, alteplase) in a Korean medical center. Methods: We retrospectively reviewed the clinical data of the patients who were treated with thrombolytic agents (urokinase and alteplase) because of massive PTE. Results: A total of 40 patients were included: 16 (40%) treated with urokinase and 24 (60%) with alteplase. The patients treated with alteplase showed a shorter duration of using vasopressor agents than did the patients who were given urokinase, but the duration of mechanical ventilation, the length of the ICU stay and the hospital stay were not different between the thrombolytic agents. Five patients treated with urokinase and eight patients treated with alteplase died (p=0.565): One patient in the urokinase group and four patients in the alteplase group died due to pulmonary thromboembolism. Bleeding complications after thrombolysis were observed in 3 patients (7.5%) treated with urokinase and in 11 (27.5%) patients treated with alteplase (p=0.079). Major bleeding complication occurred in 2 patients who were treated with alteplase. Conclusion: Urokinase seems to have fewer bleeding complications with an equivalent efficacy, as compared to alteplase, in Korean patients who suffer with massive pulmonary thromboembolism.

Safety Profile of Transcranial Near-Infrared Laser Therapy Administered in Combination With Thrombolytic Therapy to Embolized Rabbits

Transcranial near-infrared laser therapy (TLT) is currently under investigation in a pivotal clinical trial that excludes thrombolytic therapy. To determine if combining tissue plasminogen activator (tPA; Alteplase) and TLT is safe, this study assessed the safety profile of TLT administered alone and in combination with Alteplase. The purpose for this study is to determine if the combination of TLT and thrombolysis should be investigated further in a human clinical trial. We determined whether postembolization treatment with TLT in the absence or presence of tPA would affect measures of hemorrhage or survival after large clot embolism-induced strokes in New Zealand white rabbits. TLT did not significantly alter hemorrhage incidence after embolization, but there was a trend for a modest reduction of hemorrhage volume (by 65%) in the TLT-treated group compared with controls. Intravenous administration of tPA, using an optimized dosing regimen, significantly increased hemorrhage incidence by 160%. The tPA-induced increase in hemorrhage incidence was not significantly affected by TLT, although there was a 30% decrease in hemorrhage incidence in combination-treated rabbits. There was no effect of TLT on hemorrhage volume measured in tPA-treated rabbits and no effect of any treatment on 24-hour survival rate. In the embolism model, TLT administration did not affect the tPA-induced increase in hemorrhage incidence. TLT may be administered safely either alone or in combination with tPA because neither treatment affected hemorrhage incidence or volume. Our results support the study of TLT in combination with Alteplase in patients with stroke.

Alteplase for Patients With Ictus: the Dilemma Persists

To the Editor: Therapeutic usefulness of alteplase in patients with ischemic stroke is a complex topic. Perhaps some clinical trials with good methodology exist; they are very different in patients, treatment and results. From a wide point of view, as of the Wardlaw et al metaanalysis,1 alteplase administration could increase all-cause mortality in 1.9% (95% CI, −0.6% to 4.8%). In spite of this, it favors recovery from stroke, so 5.5% more patients …

The Effect of Primary Percutaneous Coronary Intervention after the Administration of Tirofiban Alone or Tirofiban Combined with Low dose Alteplase in Patients with Acute Myocardial Infarction on ST Elevation Resolution, TIMI Flow and Short-Term Clinical Outcomes

Background and Objectives：The combination of platelet glycoprotein IIb/IIIa inhibitors and a low dose thrombolytic agent may produce early Thrombolysis In Myocardial Infarction (TIMI) 3 flow and a high rate of ST elevation resolution in an ST elevation acute myocardial infarction (STEMI). The clinical effect of tirofiban combined with low dose alteplase, prior to primary percutaneous coronary intervention (PCI) in STEMI, were evaluated on the ST elevation resolution, TIMI flow and 30-day clinical outcomes. Subjects and Methods：Following aspirin, clopidogrel and standard heparin, 45 patients with STEMI were randomized into 2 groups; tirofiban administration (Group I; n=23, 64±10 years; 15 male) or combined administration of tirofiban with 40 mg alteplase prior to primary PCI (Group II; n=22, 59±11 years; 19 male). The pre- and post-interventional TIMI flow grades, ST elevation resolution and bleeding complications were compared between the two groups. The major adverse cardiac events (MACE) were compared between the two groups during 30-days of clinical follow-up. Results： Group II had a higher pre-interventional TIMI flow (TIMI flow≥2: 34.8% vs. 90.9%, p<0.0001) and rate of ST elevation resolution (49.0±27.8% vs. 66.6±27.2%, p=0.045) than Group I. A major bleeding complication developed in 1 (5.0%) Group II patient, and minor bleeding complications developed 1 patient from each group (Group I; 9.5% vs. Group II; 10%, p=0.959). Conclusion：Combined administration of tirofiban with alteplase prior to primary PCI leads to a higher TIMI flow and more frequent ST elevation resolution, without bleeding complications, compared to a single administration of tirofiban. (Korean Circulation J 2005;35:362-368)

Efficacy of alteplase thrombolysis for ED treatment of pulmonary embolism with shock.

Our objective was to assess efficacy and tolerance of thrombolysis using 0.6 mg/kg of Alteplase in patients with massive pulmonary embolism defined as the association of a pulmonary embolism with shock. We retrospectively included 21 patients presenting with a massive pulmonary embolism confirmed by either scintigraphy or spiral computed tomography. Patients were treated on the basis of a standard rationale followed by thrombolysis with 0.6 mg/kg Alteplase over a period of 15 minutes. Hospital mortality, vital signs before and 2 hours after thrombolysis, and incidence of hemorrhagic events were recorded. Five patients (23.8%) died, 4 of these deaths occurred during the first 4 hours after hospital admission. Systolic and diastolic blood pressure (Sp02) were significantly improved 2 hours after the beginning of thrombolysis. Five minor hemorrhagic events occurred. This study demonstrates that for patients with pulmonary embolism and shock, a bolus treatment with Alteplase is potentially effective and well tolerated.