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Stroke thrombolysis research archive Dec 2007:-

Prevalence and prognostic implications of ST-segment deviations from ambulatory Holter monitoring after ST-segment elevation myocardial infarction treated with either fibrinolysis or primary percutaneous coronary intervention (a Danish Trial in Acute Myocardial Infarction-2 Substudy). stroke thrombolysis research related articles

Prevalence and prognostic implications of ST-segment deviations from ambulatory Holter monitoring after ST-segment elevation myocardial infarction treated with either fibrinolysis or primary percutaneous coronary intervention (a Danish Trial in Acute Myocardial Infarction-2 Substudy).

Am J Cardiol. 2007 Sep 15;100(6):937-43

stroke thrombolysis Authors: Idorn L, Høfsten DE, Wachtell K, Mølgaard H, Egstrup K,

Ambulatory Holter monitoring has been shown to be useful in stratifying cardiovascular risk after acute myocardial infarction. However, it remains unclear whether ST-segment deviations might predict clinical outcomes in a population treated with primary percutaneous coronary intervention (PCI) compared with thrombolysis. Holter monitoring was initiated at discharge from ST-segment elevation myocardial infarction in 958 patients followed for 2,773 patient-years, randomized to immediate revascularization with either fibrinolysis (n=474) or PCI (n=484). The primary end point was all-cause mortality, and the secondary end point was a composite of death, reinfarction, and disabling stroke. The prevalences of ST-segment depression (STd) and ST-segment elevation (STe) were similar in patients treated with fibrinolysis or PCI (both p=NS). During follow-up, 58 patients died (primary PCI vs fibrinolysis hazard ratio 0.74, p=0.25). The secondary end point was reached in 113 patients (primary PCI vs fibrinolysis hazard ratio 0.66, p=0.03). In fibrinolysis-treated patients, mortality and the secondary end point were significantly higher in patients with STe (both end points p<0.001), an association that remained statistically significant after adjustment for age, gender, anterior infarction, beta-blocker treatment, left ventricular systolic function, and STd (p=0.03 and p=0.005, respectively). Significant associations were not observed for STd. In PCI-treated patients, there was no association between either STe or STd and outcome. In conclusion, immediate revascularization with PCI during STe myocardial infarction does not affect the subsequent prevalence of ST-segment deviation compared with fibrinolysis. However, although STe is an independent predictor of mortality and nonfatal major cardiovascular events in patients treated with fibrinolysis, it does not predict outcome after PCI, perhaps because of more complete revascularization.

stroke thrombolysis research PMID: 17826373 [PubMed - indexed for MEDLINE]Long-term outcome after thrombolysis in telemedical stroke care. stroke thrombolysis research related articles

Long-term outcome after thrombolysis in telemedical stroke care.

Neurology. 2007 Aug 28;69(9):898-903

stroke thrombolysis Authors: Schwab S, Vatankhah B, Kukla C, Hauchwitz M, Bogdahn U, Fürst A, Audebert HJ, Horn M,

BACKGROUND: IV thrombolysis represents the most effective acute stroke therapy. However, it is almost exclusively performed in stroke centers and is not available in most community areas. The Telemedical Pilot Project for Integrative Stroke Care (TEMPiS) was started in February 2003. Twelve community hospitals with no or very limited stroke thrombolysis experience and two stroke centers were connected via a network providing online neurologic examination and transfer of neuroradiologic scans. Following recently published preliminary results on acute phase safety of telethrombolysis, the present study reports on its long-term functional outcome. METHODS: Modified Rankin Scale (mRS), Barthel Index (BI), and mortality rate were prospectively collected 3 and 6 months after IV thrombolysis in patients of community network hospitals (telemedical group) and the stroke centers. Values of 95/100 for the BI and 0/1 for the mRS were defined as a favorable outcome. RESULTS: Over the first 22 months, 170 patients were treated with tPA in the telemedical hospitals and 132 in the stroke center hospitals. Mortality rates were 11.2% vs 11.5% at 3 months (p = 0.55) and 14.2% vs 13% at 6 months (p = 0.45). A good functional outcome after 6 months was found in 39.5% of the telemedical hospitals vs 30.9% of the stroke centers (p = 0.10) for the mRS and 47.1% vs 44.8% (p = 0.44) regarding the BI. CONCLUSIONS: Mortality rates and functional outcomes for telemedicine-linked community hospitals and stroke centers were similar and comparable to the results from randomized trials.

stroke thrombolysis research PMID: 17724293 [PubMed - indexed for MEDLINE]Seizures during stroke thrombolysis heralding dramatic neurologic recovery. stroke thrombolysis research related articles

Seizures during stroke thrombolysis heralding dramatic neurologic recovery.

Neurology. 2007 Jul 24;69(4):409-10

stroke thrombolysis Authors: Seeck M, Vulliemoz S

stroke thrombolysis research PMID: 17646639 [PubMed - indexed for MEDLINE]Does MR imaging improve precision in stroke thrombolysis trials? stroke thrombolysis research related articles

Does MR imaging improve precision in stroke thrombolysis trials?

Radiology. 2007 Aug;244(2):323-4

stroke thrombolysis Authors: Hackney DB

stroke thrombolysis research PMID: 17641357 [PubMed - indexed for MEDLINE]Primary percutaneous coronary intervention compared with fibrinolysis for myocardial infarction in diabetes mellitus: results from the Primary Coronary Angioplasty vs Thrombolysis-2 trial. stroke thrombolysis research related articles

Primary percutaneous coronary intervention compared with fibrinolysis for myocardial infarction in diabetes mellitus: results from the Primary Coronary Angioplasty vs Thrombolysis-2 trial.

Arch Intern Med. 2007 Jul 9;167(13):1353-9

stroke thrombolysis Authors: Timmer JR, Ottervanger JP, de Boer MJ, Boersma E, Grines CL, Westerhout CM, Simes RJ, Granger CB, Zijlstra F,

BACKGROUND: There is growing evidence for a clinical benefit of primary percutaneous coronary intervention (PCI) compared with fibrinolysis; however, whether the treatment effect is consistent among patients with diabetes mellitus is unclear. We compared PCI with fibrinolysis for treatment of ST-segment elevation myocardial infarction in patients with diabetes mellitus. METHODS: A pooled analysis of individual patient data from 19 trials comparing primary PCI with fibrinolysis for treatment of ST-segment elevation myocardial infarction was performed. Trials that enrolled at least 50 patients with ST-segment elevation myocardial infarction and randomized patients to receive either primary PCI or fibrinolysis were considered for inclusion in our study. Clinical end points were total deaths, recurrent infarction, death or nonfatal recurrent infarction, and stroke, measured 30 days after randomization. RESULTS: Of 6315 patients, 877 (14%) had diabetes. Thirty-day mortality (9.4% vs 5.9%; P < .001) was higher in patients with diabetes. Mortality was lower after primary PCI compared with fibrinolysis in both patients with diabetes (unadjusted odds ratio, 0.49; 95% confidence interval, 0.31-0.79; P = .004) and without diabetes (unadjusted odds ratio, 0.69; 95% confidence interval, 0.54-0.86, P = .001), with no evidence of heterogeneity of treatment effect (P = .24 for interaction). Recurrent infarction and stroke were also reduced after primary PCI in both patient groups. After multivariable analysis, primary PCI was associated with decreased 30-day mortality in patients with and without diabetes, with a point estimate of greater benefit in diabetic patients. CONCLUSIONS: Diabetic patients with ST-segment elevation myocardial infarction treated with reperfusion therapy have increased mortality compared with patients without diabetes. The beneficial effects of primary PCI compared with fibrinolysis in diabetic patients are consistent with effects in nondiabetic patients.

stroke thrombolysis research PMID: 17620527 [PubMed - indexed for MEDLINE]Mast cell stabilization reduces hemorrhage formation and mortality after administration of thrombolytics in experimental ischemic stroke. stroke thrombolysis research related articles

Mast cell stabilization reduces hemorrhage formation and mortality after administration of thrombolytics in experimental ischemic stroke.

Circulation. 2007 Jul 24;116(4):411-8

stroke thrombolysis Authors: Strbian D, Karjalainen-Lindsberg ML, Kovanen PT, Tatlisumak T, Lindsberg PJ

BACKGROUND: Thrombolysis with tissue plasminogen activator (tPA) improves stroke outcome, but hemorrhagic complications and reperfusion injury occasionally impede favorable prognosis after vessel recanalization. Perivascularly located cerebral mast cells (MCs) release on degranulation potent vasoactive, proteolytic, and fibrinolytic substances. We previously found MCs to increase ischemic and hemorrhagic brain edema and neutrophil accumulation. This study examined the role of MCs in tPA-mediated hemorrhage formation (HF) and reperfusion injury. METHODS AND RESULTS: Exposure to tPA in vitro induced strong MC degranulation. In vivo experiments in a focal cerebral ischemia/reperfusion model in rats showed 70- to 100-fold increase in HF after postischemic tPA administration (P<0.001). Pharmacological MC stabilization with cromoglycate led to significant reduction in tPA-mediated HF at 3 (97%), 6 (76%), and 24 hours (96%) compared with controls (P<0.01, P<0.001, and P<0.01, respectively). Furthermore, genetically modified MC-deficient rats showed similarly robust reduction of tPA-mediated HF at 6 (92%) and 24 (89%) hours compared with wild-type littermates (P<0.01 and P<0.001, respectively). MC stabilization and MC deficiency also significantly reduced other hallmarks of reperfusion injury, such as brain swelling and neutrophil infiltration. These effects of cromoglycate and MC deficiency translated into significantly better neurological outcome (P<0.01 and P<0.05, respectively) and lower mortality (P<0.05 and P<0.05, respectively) after 24 hours. CONCLUSIONS: MCs appear to play an important role in HF and reperfusion injury after tPA administration. Pharmacological stabilization of MCs could offer a novel type of therapy to improve the safety of administration of thrombolytics.

stroke thrombolysis research PMID: 17606844 [PubMed - indexed for MEDLINE]Consent for intravenous thrombolysis in acute stroke: review and future directions. stroke thrombolysis research related articles

Consent for intravenous thrombolysis in acute stroke: review and future directions.

Arch Neurol. 2007 Jun;64(6):785-92

stroke thrombolysis Authors: White-Bateman SR, Schumacher HC, Sacco RL, Appelbaum PS

Intravenous thrombolysis with recombinant tissue plasminogen activator is the standard of care for the treatment of acute ischemic stroke within 3 hours after stroke onset. Randomized clinical studies have demonstrated that intravenous thrombolysis improves functional outcomes but is not lifesaving. Complications of intravenous thrombolysis include severe intracranial hemorrhage that may be lethal. As with any therapy, consent cannot be assumed in the decision to use intravenous thrombolysis. Currently, there is no standardized method to estimate the capacity of patients with acute stroke, and empirical data for this patient population are limited. It is our position that candidates for intravenous thrombolysis should be properly assessed for their capacity to give direct consent before another form of consent is sought. We believe this would best be achieved by the development and standardization of a procedure for capacity assessment specifically for use in patients with acute stroke. To this end, we review the elements of informed consent, the legal standards for competence that a candidate for intravenous thrombolysis must meet to consent to treatment, recommendations for assessing capacity to give direct informed consent with attention to difficulties presented by the acute stroke setting, alternatives to direct consent with their inherent moral difficulties, and potential directions for research and discourse on capacity assessment in acute stroke.

stroke thrombolysis research PMID: 17562926 [PubMed - indexed for MEDLINE]Efficacy and safety of enoxaparin versus unfractionated heparin in patients with ST-segment elevation myocardial infarction also treated with clopidogrel. stroke thrombolysis research related articles

Efficacy and safety of enoxaparin versus unfractionated heparin in patients with ST-segment elevation myocardial infarction also treated with clopidogrel.

J Am Coll Cardiol. 2007 Jun 12;49(23):2256-63

stroke thrombolysis Authors: Sabatine MS, Morrow DA, Dalby A, Pfisterer M, Duris T, Lopez-Sendon J, Murphy SA, Gao R, Antman EM, Braunwald E,

OBJECTIVES: The purpose of this study was to determine the efficacy and safety of enoxaparin (ENOX) versus unfractionated heparin (UFH) in patients with ST-segment elevation myocardial infarction (STEMI) receiving fibrinolytic therapy with and without clopidogrel. BACKGROUND: The efficacy and safety of ENOX and clopidogrel given together in STEMI remains to be defined. METHODS: We compared the rates of major adverse cardiovascular events (MACE) as well as the rates of bleeding in medically managed patients randomized to ENOX versus UFH in the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial, stratified by concomitant clopidogrel use. RESULTS: Enoxaparin significantly reduced the rate of the composite of death, recurrent myocardial infarction, myocardial ischemia, or stroke, compared with UFH, both in patients (n = 2,173) treated with clopidogrel (10.8% vs. 13.9%, adjusted odds ratio [OR(adj)] 0.70, p = 0.013) and in patients (n = 12,918) not treated with clopidogrel (13.3% vs. 15.3%, OR(adj) 0.85, p = 0.003) with no evidence of heterogeneity (p(interaction) = 0.21). The excess risk of TIMI major bleeding with ENOX versus UFH was numerically but not statistically significantly higher in patients treated with clopidogrel (2.7% vs. 1.0%) versus those who were not (2.1% vs. 1.2%) (p(interaction) = 0.61). Net clinical benefit (MACE and major bleeding) favored treatment with ENOX over UFH, either with concomitant clopidogrel (absolute risk reduction 2.4%, 95% confidence interval [CI] -0.5% to 5.3%) or without (absolute risk reduction 1.7%, 95% CI 0.5% to 3.0%) (p(interaction) = 0.61). CONCLUSIONS: In patients with STEMI receiving fibrinolytic therapy, the net benefit of ENOX is similar in patients who are and are not treated with clopidogrel. The totality of trial data suggest that the combination of a fibrinolytic, aspirin, clopidogrel, and ENOX offers an attractive pharmacologic reperfusion strategy in STEMI.

stroke thrombolysis research PMID: 17560290 [PubMed - indexed for MEDLINE]The impact of renal dysfunction on outcomes in the ExTRACT-TIMI 25 trial. stroke thrombolysis research related articles

The impact of renal dysfunction on outcomes in the ExTRACT-TIMI 25 trial.

J Am Coll Cardiol. 2007 Jun 12;49(23):2249-55

stroke thrombolysis Authors: Fox KA, Antman EM, Montalescot G, Agewall S, SomaRaju B, Verheugt FW, Lopez-Sendon J, Hod H, Murphy SA, Braunwald E

OBJECTIVES: The ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial provided the opportunity to evaluate the impact of renal dysfunction on outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and compare enoxaparin (ENOX) and unfractionated heparin (UFH). BACKGROUND: It is unclear how renal dysfunction influences the balance between benefit and risk of antithrombotic therapy. METHODS: In the ExTRACT-TIMI 25 trial, 20,479 patients were randomized to UFH or ENOX. A reduced ENOX dose was administered to patients age > or =75 years and those with an estimated creatinine clearance (CrCl) <30 ml/min. RESULTS: A powerful relationship was observed between the severity of renal dysfunction (per 10 ml/min decrement in CrCl) and death, stroke, intracranial hemorrhage, and major and minor bleeding (p < 0.001 for each). There was a progressive increase in the treatment benefit with ENOX on death or nonfatal myocardial infarction (p < 0.01) with better renal function. Net clinical benefit (death, nonfatal MI, or nonfatal major bleeding) was significantly superior with ENOX (p < 0.001) for patients with a CrCl >60 ml/min (79.1% of the study population). Major bleeding and intracranial hemorrhage did not differ for patients with preserved renal function (CrCl >90 ml/min), but in those with renal dysfunction there was a progressively greater increase in the risk of major and minor bleeding with ENOX. CONCLUSIONS: Enoxaparin was superior to UFH for the majority of subjects. With more severe renal dysfunction, the net clinical benefit between ENOX and UFH did not differ, despite the rise in adverse events in both treatment groups. Future studies should take renal dysfunction into account when assessing antithrombotic regimens.

stroke thrombolysis research PMID: 17560289 [PubMed - indexed for MEDLINE]Accuracy of serial National Institutes of Health Stroke Scale scores to identify artery status in acute ischemic stroke. stroke thrombolysis research related articles

Accuracy of serial National Institutes of Health Stroke Scale scores to identify artery status in acute ischemic stroke.

Circulation. 2007 May 22;115(20):2660-5

stroke thrombolysis Authors: Mikulik R, Ribo M, Hill MD, Grotta JC, Malkoff M, Molina C, Rubiera M, Delgado-Mederos R, Alvarez-Sabin J, Alexandrov AV,

BACKGROUND: Early recovery after intravenous thrombolysis can be observed in stroke; however, the utility of measuring clinical improvement to assess artery status has not been established. We sought to determine the accuracy of serial National Institutes of Health Stroke Scale (NIHSS) scores to detect complete early recanalization of the middle cerebral artery. METHODS AND RESULTS: Data from the CLOTBUST trial (Combined Lysis of Thrombus in Brain Ischemia Using Transcranial Ultrasound and Systemic tPA) were used to determine the most sensitive and specific NIHSS-derived parameter to identify complete recanalization. Then, reproducibility was tested against a separate patient population (Barcelona data set). NIHSS scores were determined before tissue plasminogen activator bolus and at 60 and 120 minutes in both data sets. Receiver operating characteristic curves were used to compare test performance. The accuracy of individual cutoffs was demonstrated by sensitivity, specificity, and positive and negative predictive values. A total of 122 patients in the CLOTBUST data set and 98 in the Barcelona data set received 0.9 mg/kg intravenous tissue plasminogen activator [mean age 69+/-12 versus 72+/-12 years, 57% male versus 51% male, median NIHSS 16 versus 17 points, mean time from onset to treatment 140+/-32 versus 177+/-59 minutes, and complete recanalization of the middle cerebral artery in 19% versus 17%). For identification of recanalization, an NIHSS score reduction of > or = 40% offered the best tradeoff, with sensitivity, specificity, positive predictive value, and negative predictive value of 65%, 85%, 50%, and 91% at 60 minutes and 74%, 80%, 58%, and 89% at 120 minutes, respectively. Test performance was equal in the Barcelona data set. CONCLUSIONS: Relative changes in serial NIHSS scores can serve as a simple clinical indicator of arterial status after intravenous thrombolysis. Accuracy parameters are affected by the process of recanalization and its varying clinical significance.

stroke thrombolysis research PMID: 17502578 [PubMed - indexed for MEDLINE]Acute [corrected] stroke thrombolysis: an update [corrected] stroke thrombolysis research related articles

Acute [corrected] stroke thrombolysis: an update [corrected]

Prog Cardiovasc Dis. 2007 May-Jun;49(6):430-8

stroke thrombolysis Authors: Mehdiratta M, Caplan LR

Acute stroke therapy took a major step forward in 1996 after the approval of Intravenous (IV) tissue plasminogen activator (t-PA) by the US Food and Drug Administration for patients presenting within 3 hours of the onset of stroke symptoms. Since that time, there have been considerable advances in imaging techniques as well as the advent of devices to help in the management of acute stroke patients. As a result, the arsenal to treat acute stroke has grown, and the field of stroke as a subspecialty of neurology has emerged. Despite these advances, only 3% to 8% of eligible patients with acute stroke in the United States are administered thrombolytics.(1) We herein review the use of thrombolytics in stroke and provide an overview of the imaging advances, new devices, and recent trials that are shaping modern stroke therapy. Finally, we provide a practical approach to the management of acute stroke, specifically for the practicing cardiologist, who may encounter stroke during cardiac catheterization, post myocardial infarction (MI), and in a variety of other settings.

stroke thrombolysis research PMID: 17498523 [PubMed - indexed for MEDLINE]Use of thrombolysis in acute ischemic stroke: analysis of the Nationwide Inpatient Sample 1999 to 2004. stroke thrombolysis research related articles

Use of thrombolysis in acute ischemic stroke: analysis of the Nationwide Inpatient Sample 1999 to 2004.

Ann Emerg Med. 2007 Aug;50(2):99-107

stroke thrombolysis Authors: Schumacher HC, Bateman BT, Boden-Albala B, Berman MF, Mohr JP, Sacco RL, Pile-Spellman J

STUDY OBJECTIVE: The aim of this study is to characterize hospital and patient characteristics associated with administration of thrombolysis in acute ischemic stroke patients in the United States. METHODS: This retrospective, observational, cohort study used data from the Nationwide Inpatient Sample, an administrative discharge database. A total of 366,194 hospitalizations admitted through the emergency department with a primary diagnosis of acute ischemic stroke were selected for analysis. The primary outcome considered in this study is whether the patient received thrombolytic therapy on hospital day 0 or 1. RESULTS: Thrombolysis was used in 1.12% (95% confidence interval [CI] 0.95% to 1.32%) of ischemic stroke hospitalizations. Most hospitals (69.5%; 95% CI 68.4% to 70.6%) treating ischemic stroke patients did not use thrombolysis during the study period. For the hospitals that used thrombolysis, the mean annual number of patients treated with thrombolysis per hospital was 3.06 (95% CI 2.68 to 3.44). In the binary logistic regression analysis, hospital characteristics associated with high use of thrombolysis were teaching hospital status and increasing number of stroke patients treated annually. Patient characteristics associated with higher use of thrombolysis were age younger than 55 years, male sex, and low comorbidity as measured by the modified Charlson Index; white race; and private self-pay health insurance. CONCLUSION: Use of thrombolysis for ischemic stroke in the United States from 1999 to 2004 was infrequent and showed significant differences, depending on hospital and patient demographic characteristics.

stroke thrombolysis research PMID: 17478010 [PubMed - indexed for MEDLINE]Recanalization after intravenous thrombolysis: does a recanalization time window exist? stroke thrombolysis research related articles

Recanalization after intravenous thrombolysis: does a recanalization time window exist?

Neurology. 2007 Apr 24;68(17):1364-8

stroke thrombolysis Authors: Wunderlich MT, Goertler M, Postert T, Schmitt E, Seidel G, Gahn G, Samii C, Stolz E, ,

BACKGROUND: To evaluate the time course of major vessel recanalization under IV thrombolysis in relation to functional outcome in acute ischemic stroke. METHODS: A total of 99 patients with an acute anterior circulation vessel occlusion who underwent IV thrombolysis were included. All patients had a standardized admission and follow-up procedure. Color-coded duplex sonography was performed on admission, 30 minutes after thrombolysis, and at 6 and 24 hours after onset of symptoms. Recanalization was classified as complete, partial, and absent. Functional outcome was rated with the modified Rankin Scale on day 30. RESULTS: Complete recanalization occurred significantly more frequently in patients with multiple branch occlusions compared to those with mainstem occlusion (OR 5.33; 95% CI, 2.18 to 13.05; p < 0.0001) and was associated with lower NIH Stroke Scale (NIHSS) scores (p < 0.001). Not the specific time point of recanalization at 6 or 24 hours after stroke onset, but recanalization per se within 24 hours (OR 7.8; 95% CI 2.2 to 28.2; p = 0.002) was significantly associated with a favorable outcome. Multivariate analysis revealed recanalization at any time within 24 hours and NIHSS scores on days 1 and 7 together explaining 75% of the functional outcome variance 30 days after stroke. CONCLUSIONS: Complete recanalization up to 24 hours after stroke onset is significantly associated with the short-term clinical course and functional outcome 30 days after acute stroke.

stroke thrombolysis research PMID: 17452580 [PubMed - indexed for MEDLINE]Slow progressive acceptance of intravenous thrombolysis for patients with stroke by rural primary care physicians. stroke thrombolysis research related articles

Slow progressive acceptance of intravenous thrombolysis for patients with stroke by rural primary care physicians.

Arch Neurol. 2007 Apr;64(4):518-21

stroke thrombolysis Authors: Leira EC, Pary JK, Davis PH, Grimsman KJ, Adams HP

BACKGROUND: In the rural United States, patients with stroke are usually first evaluated locally by a nonneurologist physician (NNP) before treatment is determined. OBJECTIVE: To determine the evolution of NNPs' familiarity and attitudes about using recombinant tissue plasminogen activator (rtPA) since this therapy has been approved. DESIGN: Cross-sectional design using 2 similar surveys mailed in 1997 and 2003 to all primary care, family, internal, and emergency medicine physicians in the state of Iowa (1582 and 1679 physicians, respectively). PARTICIPANTS: All NNPs (primary care, internal, and emergency medicine) practicing in the state of Iowa. MAIN OUTCOME MEASURES: Comparison of 1997 and 2003 aggregate responses to questions about familiarity and willingness to use rtPA to treat patients who have had an acute ischemic stroke. RESULTS: The willingness of NNPs to use rtPA to treat acute ischemic stroke increased from 18% to 32% between 1997 and 2003. The number of NNPs who were very familiar with the National Institutes of Health Stroke Scale increased from 1% to 13%. Compared with physicians in 1997, more physicians in 2003 knew that prolonged international normalized ratios (42% vs 61%) or excessively high blood pressures (61% vs 78%) were contraindications for the use of rtPA. Still, half of the respondents perceived that they were inadequately exposed to educational material about rtPA during these years. Most expressed preference for personal methods of delivery for future educational efforts. CONCLUSIONS: The familiarity and comfort among NNPs with the administration of rtPA is still relatively low in rural settings. The improvement observed between the years 1997 and 2003 is encouraging. The responses suggest that NNPs' acceptance of rtPA can be further improved with educational campaigns involving personal methods of delivery.

stroke thrombolysis research PMID: 17420312 [PubMed - indexed for MEDLINE]Symptomatic intracranial stenosis: cerebrovascular complications from elective stent placement. stroke thrombolysis research related articles

Symptomatic intracranial stenosis: cerebrovascular complications from elective stent placement.

Radiology. 2007 Apr;243(1):188-97

stroke thrombolysis Authors: Jiang WJ, Du B, Leung TW, Xu XT, Jin M, Dong KH

PURPOSE: To retrospectively evaluate the cerebrovascular complications from elective stent placement for symptomatic intracranial stenosis and to explore preliminarily which factors are associated with complications. MATERIALS AND METHODS: Institutional ethics committee approval was obtained, with waiver of informed consent. Records were reviewed of 181 consecutive elective stent placement procedures in 169 patients (mean age, 51.8 years; 142 male and 27 female patients) with symptomatic intracranial stenosis of more than 50% diameter reduction. Complications were evaluated. Fisher exact or chi(2) tests were used to assess statistical differences between rates for discrete variables. Stratification analysis was used to assess the significant relationship (P < .05) between a potential risk factor and a complication. RESULTS: Complications occurred in 20 patients (11.8%) of 169 patients: Ten patients (5.9%) had stroke (four patients had symptomatic intracranial hemorrhages [ICHs], and two of these patients died; six patients had ischemic strokes). Six patients had target-lesion thrombosis for which intrathrombus thrombolysis resulted in early complete patency without sequelae, two had asymptomatic ICHs, one had transient ischemic attack, and one had asymptomatic dissection. Perioperative noncompliance with antiplatelet therapy was found to be significantly associated with target-lesion thrombosis (two of eight patients [noncompliance] vs four of 161 patients [compliance], P = .027). Stratification analysis revealed a significant correlation between the use of double stents for a lesion and ICH (P = .005). CONCLUSION: Cerebrovascular complications from elective stent placement for intracranial stenosis are diverse. The use of double stents for a lesion is an independent risk factor for ICH. Perioperative noncompliance with antiplatelet therapy is associated with a higher frequency of target-lesion thrombosis.

stroke thrombolysis research PMID: 17392253 [PubMed - indexed for MEDLINE]Leukoaraiosis and intracerebral hemorrhage after thrombolysis in acute stroke. stroke thrombolysis research related articles

Leukoaraiosis and intracerebral hemorrhage after thrombolysis in acute stroke.

Neurology. 2007 Mar 27;68(13):1020-4

stroke thrombolysis Authors: Palumbo V, Boulanger JM, Hill MD, Inzitari D, Buchan AM,

OBJECTIVES: To evaluate whether the presence of leukoaraiosis or multiple lacunes is associated with symptomatic intracerebral hemorrhage (ICH) and 90-day outcome after thrombolytic treatment with tissue plasminogen activator (tPA). METHODS: Data were from a Canadian national registry of thrombolyzed patients with ischemic stroke. A total of 820 scans were assessed, blind to clinical features, for the presence of severe vs no/moderate leukoaraiosis, and of multiple (>2) vs no/single lacunar infarcts. Logistic regression was used to determine if an independent interaction existed between the presence and degree of leukoaraiosis/lacunes and risk of symptomatic ICH, and to evaluate the predictive role of leukoaraiosis and lacunes in relation to 90-day outcome. RESULTS: An overall symptomatic ICH rate of 3.5% was observed. The rate of symptomatic ICH increased up to 10% in patients with severe leukoaraiosis and multiple lacunes. A significant association was observed between ICH risk and either severe leukoaraiosis (RR = 2.7 [95% CI 1.1 to 6.5]) or multiple lacunes (RR = 3.4 [95% CI 1.5 to 7.6]). Patients with multiple lacunes, but not leukoaraiosis, had higher mortality at 90 days compared to those with one or no lacunes (OR = 2.9, 95% CI 1.3 to 6.2, p = 0.008). No difference was observed in the good outcome rate among patients with and without leukoaraiosis or lacunes or both. CONCLUSION: The presence of small vessel disease on CT scan does not affect overall clinical outcome at 3 months in routine community use of tPA for ischemic stroke. A significant increase in the risk of symptomatic ICH is observed.

stroke thrombolysis research PMID: 17389306 [PubMed - indexed for MEDLINE]Sex as a predictor of outcomes in patients treated with thrombolysis for acute stroke. stroke thrombolysis research related articles

Sex as a predictor of outcomes in patients treated with thrombolysis for acute stroke.

Neurology. 2007 Mar 13;68(11):842-8

stroke thrombolysis Authors: Elkind MS, Prabhakaran S, Pittman J, Koroshetz W, Jacoby M, Johnston KC,

OBJECTIVE: To determine the association between sex and functional outcomes after thrombolytic treatment for acute ischemic stroke in the context of a clinical trial. METHODS: We analyzed predictors of outcome among patients treated with recombinant tissue plasminogen activator (rtPA) in the Glycine Antagonist in Neuroprotection for Patients with Acute Stroke Americas trial, a multicenter, randomized, double-blind, placebo-controlled study of a putative neuroprotectant. RESULTS: Among 1,367 trial patients, 333 (24%) were treated with rtPA within 3 hours. The proportion of patients achieving good functional outcomes at 3 months differed by sex (47.5% of men vs 30.3% of women had Barthel Index [BI] > or = 95; 32.2% of men vs 23.4% of women had modified Rankin Score [mRS] < or = 1). NIH Stroke Score was similar by sex. Men were more likely to have good functional outcomes after adjusting for relevant covariates: for BI > or = 95, adjusted odds ratio (OR) 3.28 (1.74 to 6.17); for mRS < or = 1, adjusted OR 2.12 (1.11 to 4.03). Survival was worse among men: adjusted OR 0.45 (0.20 to 1.01). Other predictors of functional outcomes included age, stroke side, severity, complications, and infections. CONCLUSIONS: Among tissue plasminogen activator-treated patients in this clinical trial population, men were approximately three times as likely to have good functional outcomes, despite elevated mortality. Thrombolysis for stroke may not reverse the tendency for women to have worse functional outcomes after stroke.

stroke thrombolysis research PMID: 17353472 [PubMed - indexed for MEDLINE]Mortality of stroke patients treated with thrombolysis: analysis of nationwide inpatient sample. stroke thrombolysis research related articles

Mortality of stroke patients treated with thrombolysis: analysis of nationwide inpatient sample.

Neurology. 2007 Feb 27;68(9):710-1; author reply 711

stroke thrombolysis Authors: Flaherty ML, Kissela B, Khatri P

stroke thrombolysis research PMID: 17328117 [PubMed - indexed for MEDLINE]Mortality of stroke patients treated with thrombolysis: analysis of nationwide inpatient sample. stroke thrombolysis research related articles

Mortality of stroke patients treated with thrombolysis: analysis of nationwide inpatient sample.

Neurology. 2007 Feb 27;68(9):710; author reply 711

stroke thrombolysis Authors: Kurth T, Heuschmann PU, Walker AM, Berger K

stroke thrombolysis research PMID: 17325289 [PubMed - indexed for MEDLINE]Assessing the effectiveness of primary angioplasty compared with thrombolysis and its relationship to time delay: a Bayesian evidence synthesis. stroke thrombolysis research related articles

Assessing the effectiveness of primary angioplasty compared with thrombolysis and its relationship to time delay: a Bayesian evidence synthesis.

Heart. 2007 Oct;93(10):1244-50

stroke thrombolysis Authors: Asseburg C, Vergel YB, Palmer S, Fenwick E, de Belder M, Abrams KR, Sculpher M

BACKGROUND: Meta-analyses of trials have shown greater benefits from angioplasty than thrombolysis after an acute myocardial infarction, but the time delay in initiating angioplasty needs to be considered. OBJECTIVE: To extend earlier meta-analyses by considering 1- and 6-month outcome data for both forms of reperfusion. To use Bayesian statistical methods to quantify the uncertainty associated with the estimated relationships. METHODS: A systematic review and meta-analysis published in 2003 was updated. Data on key clinical outcomes and the difference between time-to-balloon and time-to-needle were independently extracted by two researchers. Bayesian statistical methods were used to synthesise evidence despite differences between reported follow-up times and outcomes. Outcomes are presented as absolute probabilities of specific events and odds ratios (ORs; with 95% credible intervals (CrI)) as a function of the additional time delay associated with angioplasty. RESULTS: 22 studies were included in the meta-analysis, with 3760 and 3758 patients randomised to primary angioplasty and thrombolysis, respectively. The mean (SE) angioplasty-related time delay (over and above time to thrombolysis) was 54.3 (2.2) minutes. For this delay, mean event probabilities were lower for primary angioplasty for all outcomes. Mortality within 1 month was 4.5% after angioplasty and 6.4% after thrombolysis (OR = 0.68 (95% CrI 0.46 to 1.01)). For non-fatal reinfarction, OR = 0.32 (95% CrI 0.20 to 0.51); for non-fatal stroke OR = 0.24 (95% CrI 0.11 to 0.50). For all outcomes, the benefit of angioplasty decreased with longer delay from initiation. CONCLUSIONS: The benefit of primary angioplasty, over thrombolysis, depends on the former's additional time delay. For delays of 30-90 minutes, angioplasty is superior for 1-month fatal and non-fatal outcomes. For delays of around 90 minutes thrombolysis may be the preferred option as assessed by 6-month mortality; there is considerable uncertainty for longer time delays.

stroke thrombolysis research PMID: 17277350 [PubMed - indexed for MEDLINE]Experimental treatments for acute ischaemic stroke. stroke thrombolysis research related articles

Experimental treatments for acute ischaemic stroke.

Lancet. 2007 Jan 27;369(9558):331-41

stroke thrombolysis Authors: Sacco RL, Chong JY, Prabhakaran S, Elkind MS

Treatments for acute ischaemic stroke continue to evolve. Experimental approaches to restore cerebral perfusion include techniques to augment recanalising therapies, including combination of antiplatelet agents with intravenous thrombolysis, bridging therapy of combining intravenous with intra-arterial thrombolysis, and trials of new thrombolytic agents. Trials with MRI selection criteria are underway to expand the window of opportunity for thrombolysis. Sonothrombolysis and novel endovascular mechanical devices to retrieve or dissolve acute cerebral occlusions are being tested. Approaches to improve cerebral perfusion with other devices and induced hypertension are also being considered. Although numerous neuroprotective agents have not shown benefit, trials of hypothermia, magnesium, caffeinol, high doses of statins, and albumin are continuing. The findings of these randomised trials are anticipated to allow improved treatment of patients with acute stroke.

stroke thrombolysis research PMID: 17258673 [PubMed - indexed for MEDLINE]Established treatments for acute ischaemic stroke. stroke thrombolysis research related articles

Established treatments for acute ischaemic stroke.

Lancet. 2007 Jan 27;369(9558):319-30

stroke thrombolysis Authors: Khaja AM, Grotta JC

This article reviews the recommended management of patients presenting to accident and emergency departments with acute ischaemic stroke, and focuses on thrombolysis. The review includes initial management, recommended clinical, laboratory, and radiographic examinations. Appropriate general medical care, consisting of monitoring of oxygenation, fever, blood pressure, and blood glucose concentrations are examined. Criteria for thrombolysis with intravenous recombinant tissue plasminogen activator (rt-PA) are discussed. Complications of rt-PA therapy, such as haemorrhagic transformation and angio-oedema, are reviewed. An approach to management of rt-PA complications is outlined. Only a small percentage of acute ischaemic stroke patients meet criteria for rt-PA; therefore, alternative acute treatment strategies are also discussed. Acute medical and neurological complications in stroke patients are analysed, along with recommendations for treatment.

stroke thrombolysis research PMID: 17258672 [PubMed - indexed for MEDLINE]Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. stroke thrombolysis research related articles

Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study.

Lancet. 2007 Jan 27;369(9558):275-82

stroke thrombolysis Authors: Wahlgren N, Ahmed N, Dávalos A, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kuelkens S, Larrue V, Lees KR, Roine RO, Soinne L, Toni D, Vanhooren G,

BACKGROUND: The aim of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) was to assess the safety and efficacy of intravenous alteplase as thrombolytic therapy within the first 3 h of onset of acute ischaemic stroke. Under European Union regulations, SITS-MOST was required to assess the safety profile of alteplase in clinical practice by comparison with results in randomised controlled trials. METHODS: 6483 patients were recruited from 285 centres (50% with little previous experience in stroke thrombolysis) in 14 countries between 2002 and 2006 for this prospective, open, monitored, observational study. Primary outcomes were symptomatic (a deterioration in National Institutes of Health stroke scale score of >or=4) intracerebral haemorrhage type 2 within 24 h and mortality at 3 months. We compared mortality, the proportion of patients with symptomatic intracerebral haemorrhage as per the Cochrane definition, and functional outcome at 3 months with relevant pooled results from randomised controlled trials. FINDINGS: Baseline characteristics of patients in SITS-MOST were much the same as those in the pooled randomised controlled trials. At 24 h, the proportion of patients with symptomatic intracerebral haemorrhage (per the SITS-MOST protocol) was 1.7% (107/6444; 95% CI 1.4-2.0); at 7 days, the proportion with the same condition as per the Cochrane definition was 7.3% (468/6438; 6.7-7.9) compared with 8.6% (40/465; 6.3-11.6) in the pooled randomised controlled trials. The mortality rate at 3 months in SITS-MOST was 11.3% (701/6218; 10.5-12.1) compared with 17.3% (83/479; 14.1-21.1) in the pooled randomised controlled trials. INTERPRETATION: These data confirm that intravenous alteplase is safe and effective in routine clinical use when used within 3 h of stroke onset, even by centres with little previous experience of thrombolytic therapy for acute stroke. The findings should encourage wider use of thrombolytic therapy for suitable patients treated in stroke centres.

stroke thrombolysis research PMID: 17258667 [PubMed - indexed for MEDLINE]Assessment of bleeding events in clinical trials--proposal of a new classification. stroke thrombolysis research related articles

Assessment of bleeding events in clinical trials--proposal of a new classification.

Am J Cardiol. 2007 Jan 15;99(2):288-90

stroke thrombolysis Authors: Serebruany VL, Atar D

Present classifications of bleeding events used in antithrombotic and/or antiplatelet clinical trials are based on the criteria developed by the Thrombolysis In Myocardial Infarction (TIMI) and Global Use of Strategies to Open Coronary Arteries (GUSTO) groups. Introduced more than a decade ago, the 2 classifications used the criteria to better categorize hemorrhagic events after therapy with thrombolytic agents. Recent advances in interventional cardiology, resulting in a domination of percutaneous intracoronary procedures over systemic drug-induced thrombolysis, have substantially changed the clinical characteristics and magnitude of bleeding complications. Moreover, disturbances of the coagulation cascade, as well as platelet inhibition caused directly by antithrombotic and antiplatelet agents, share very specific and well-recognized clinical features not reflected in the existing classifications. Bleeding events after aspirin or clopidogrel, and especially those after more delicate antiplatelet regimens with dipyridamole used in patients after ischemic stroke or transient ischemic attack, are impossible to classify by the present guidelines, other than categorically triaging them altogether to the "minor" category. Uniting entirely different bleeding events as "minor" under-rates their importance and diminishes affiliated risks, creating an illusion that they do not require monitoring and/or changes in antiplatelet or antithrombotic regimens. In reality, such unrecognized and unreported mild complications may transform into more serious bleeds or lead to noncompliance. Unauthorized withdrawal from antiplatelet agents in turn causes rebound platelet activation and higher risk for secondary vascular events. In conclusion, a new classification of bleeding events is introduced (the BleedScore), based on a point accumulation depending on the severity of hemorrhage, which is believed to be more suitable for the assessment of modern, more delicate antithrombotic and antiplatelet therapies, particularly for their realistic assessment in clinical trials.

stroke thrombolysis research PMID: 17223436 [PubMed - indexed for MEDLINE]Recanalization after thrombolysis in stroke patients: predictors and prognostic implications. stroke thrombolysis research related articles

Recanalization after thrombolysis in stroke patients: predictors and prognostic implications.

Neurology. 2007 Jan 2;68(1):39-44

stroke thrombolysis Authors: Zangerle A, Kiechl S, Spiegel M, Furtner M, Knoflach M, Werner P, Mair A, Wille G, Schmidauer C, Gautsch K, Gotwald T, Felber S, Poewe W, Willeit J

OBJECTIVE: To estimate rates, predictors, and prognostic importance of recanalization in an unselected series of patients with stroke treated with IV thrombolysis. METHODS: We performed a CT angiography or transcranial Doppler (TCD) follow-up examination 24 hours after IV thrombolysis in 64 patients with documented occlusion of the intracranial internal carotid or middle cerebral artery (MCA). Complete recanalization was defined by a rating of 3 on the Thrombolysis in Myocardial Infarction or 4/5 on the Thrombolysis in Brain Ischemia grading scales. Information about risk factors, clinical features, and outcome was prospectively collected by standardized procedures. RESULTS: Complete recanalization was achieved in 36 of the 64 patients (56.3%). There was a nonsignificant trend of recanalization rates to decline with a more proximal site of occlusion: 68.4% (M2 segment of MCA), 53.1% (M1 segment), and 46.2% (carotid T) (p for trend = 0.28). Frequencies of vessel reopening were markedly reduced in subjects with diabetes (9.1% vs 66.0% in nondiabetics, p < 0.001) and less so in subjects with additional extracranial carotid occlusion (p = 0.03). Finally, complete recanalization predicted a favorable stroke outcome at day 90 independently of the information provided by age, NIH Stroke Scale, and onset-to-needle time. CONCLUSIONS: We found a high rate of vessel recanalization after IV thrombolysis occlusion. However, recanalization was infrequent in patients with diabetes and extracranial carotid occlusion. Information on recanalization was a powerful, early predictor for clinical outcome.

stroke thrombolysis research PMID: 17200490 [PubMed - indexed for MEDLINE]Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis. stroke thrombolysis research related articles

Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis.

Neurology. 2007 Mar 6;68(10):737-42

stroke thrombolysis Authors: Bang OY, Saver JL, Liebeskind DS, Starkman S, Villablanca P, Salamon N, Buck B, Ali L, Restrepo L, Vinuela F, Duckwiler G, Jahan R, Razinia T, Ovbiagele B

BACKGROUND: Prestroke statin use may improve ischemic stroke outcomes, yet there is also evidence that statins and extremely low cholesterol levels may increase the risk of intracranial hemorrhage. We evaluated the independent effect of statin use and admission cholesterol level on risk of symptomatic hemorrhagic transformation (sHT) after recanalization therapy for acute ischemic stroke. METHODS: We analyzed ischemic stroke patients recorded in a prospectively maintained registry that received recanalization therapies (IV or intra-arterial fibrinolysis or endovascular embolectomy) at a university medical center from September 2002 to May 2006. The independent effect of premorbid statin use on sHT post intervention was evaluated by logistic regression, adjusting for prognostic and treatment variables known to predict increased HT risk after ischemic stroke. RESULTS: Among 104 patients, mean age was 70 years, and 49% were men. Male sex, hypertension, statin use, low total cholesterol and low-density lipoprotein (LDL) cholesterol, current smoking, elevated glucose levels, and higher admission NIH Stroke Scale (NIHSS) score were all associated with a greater risk of sHT in univariate analysis. After adjusting for covariates, low LDL cholesterol (odds ratio [OR], 0.968 per 1-mg/dL increase; 95% CI, 0.941 to 0.995), current smoking (OR, 14.568; 95% CI, 1.590 to 133.493), and higher NIHSS score (OR, 1.265 per 1-point increase; 95% CI, 1.047 to 1.529) were independently associated with sHT risk. CONCLUSIONS: Lower admission low-density lipoprotein cholesterol level with or without statin use, current smoking, and greater stroke severity are associated with greater risk for symptomatic hemorrhagic transformation after recanalization therapy for ischemic stroke.

stroke thrombolysis research PMID: 17182976 [PubMed - indexed for MEDLINE]Comparison of treatment effects between animal experiments and clinical trials: systematic review. stroke thrombolysis research related articles

Comparison of treatment effects between animal experiments and clinical trials: systematic review.

BMJ. 2007 Jan 27;334(7586):197

stroke thrombolysis Authors: Perel P, Roberts I, Sena E, Wheble P, Briscoe C, Sandercock P, Macleod M, Mignini LE, Jayaram P, Khan KS

OBJECTIVE: To examine concordance between treatment effects in animal experiments and clinical trials. Study design Systematic review. DATA SOURCES: Medline, Embase, SIGLE, NTIS, Science Citation Index, CAB, BIOSIS. STUDY SELECTION: Animal studies for interventions with unambiguous evidence of a treatment effect (benefit or harm) in clinical trials: head injury, antifibrinolytics in haemorrhage, thrombolysis in acute ischaemic stroke, tirilazad in acute ischaemic stroke, antenatal corticosteroids to prevent neonatal respiratory distress syndrome, and bisphosphonates to treat osteoporosis. Review methods Data were extracted on study design, allocation concealment, number of randomised animals, type of model, intervention, and outcome. RESULTS: Corticosteroids did not show any benefit in clinical trials of treatment for head injury but did show a benefit in animal models (pooled odds ratio for adverse functional outcome 0.58, 95% confidence interval 0.41 to 0.83). Antifibrinolytics reduced bleeding in clinical trials but the data were inconclusive in animal models. Thrombolysis improved outcome in patients with ischaemic stroke. In animal models, tissue plasminogen activator reduced infarct volume by 24% (95% confidence interval 20% to 28%) and improved neurobehavioural scores by 23% (17% to 29%). Tirilazad was associated with a worse outcome in patients with ischaemic stroke. In animal models, tirilazad reduced infarct volume by 29% (21% to 37%) and improved neurobehavioural scores by 48% (29% to 67%). Antenatal corticosteroids reduced respiratory distress and mortality in neonates whereas in animal models respiratory distress was reduced but the effect on mortality was inconclusive (odds ratio 4.2, 95% confidence interval 0.85 to 20.9). Bisphosphonates increased bone mineral density in patients with osteoporosis. In animal models the bisphosphonate alendronate increased bone mineral density compared with placebo by 11.0% (95% confidence interval 9.2% to 12.9%) in the combined results for the hip region. The corresponding treatment effect in the lumbar spine was 8.5% (5.8% to 11.2%) and in the combined results for the forearms (baboons only) was 1.7% (-1.4% to 4.7%). CONCLUSIONS: Discordance between animal and human studies may be due to bias or to the failure of animal models to mimic clinical disease adequately.

stroke thrombolysis research PMID: 17175568 [PubMed - indexed for MEDLINE]Seizures during stroke thrombolysis heralding dramatic neurologic recovery.

Seizures during stroke thrombolysis heralding dramatic neurologic recovery.

Neurology. 2006 Dec 12;67(11):2048-9

stroke thrombolysis Authors: Rodan LH, Aviv RI, Sahlas DJ, Murray BJ, Gladstone JP, Gladstone DJ

Seizures during thrombolytic therapy for ischemic stroke have not previously been described as a favorable prognostic sign. We report three patients with severe stroke (NIH Stroke Scale [NIHSS] score 15 to 20) who experienced a seizure during tissue plasminogen activator (tPA) infusion. While initially raising alarm about possible hemorrhage, the seizures heralded dramatic recovery (an immediate 15-point NIHSS score improvement after tPA; NIHSS score 0 or 1 at 24 hours). We propose that the seizures during thrombolysis may indicate cortical reperfusion and/or hyperperfusion due to early recanalization of an acutely occluded intracranial artery.

stroke thrombolysis research PMID: 17159118 [PubMed - indexed for MEDLINE]Prediction of thrombolytic efficacy in acute ischemic stroke using thin-section noncontrast CT. stroke thrombolysis research related articles

Prediction of thrombolytic efficacy in acute ischemic stroke using thin-section noncontrast CT.

Neurology. 2006 Nov 28;67(10):1846-8

stroke thrombolysis Authors: Kim EY, Heo JH, Lee SK, Kim DJ, Suh SH, Kim J, Kim DI

Thin-section noncontrast CT (NCT) can detect thrombi in large arteries and can provide a measure of thrombus composition based on Hounsfield Units (HU). A study using polyethylene tubes as a model of intracranial arteries concluded that the HUs of platelet-rich thrombi are lower than those of erythrocyte-rich thrombi. Thrombus HUs were measured by NCT in 34 patients with acute ischemic stroke before thrombolysis. Thrombi with lower HU counts were resistant to thrombolytics.

stroke thrombolysis research PMID: 17130421 [PubMed - indexed for MEDLINE]Progression of middle cerebral artery susceptibility sign on T2*-weighted images: its effect on recanalization and clinical outcome after thrombolysis. stroke thrombolysis research related articles

Progression of middle cerebral artery susceptibility sign on T2*-weighted images: its effect on recanalization and clinical outcome after thrombolysis.

AJR Am J Roentgenol. 2006 Dec;187(6):W650-7

stroke thrombolysis Authors: Kim HS, Lee DH, Choi CG, Kim SJ, Suh DC

OBJECTIVE: The middle cerebral artery (MCA) "susceptibility sign" on T2*-weighted imaging has been reported to indicate acute thrombotic occlusion. We evaluated the serial progression of this susceptibility sign on follow-up MRI and its effect on recanalization and clinical outcome after intraarterial thrombolysis. MATERIALS AND METHODS: Thirty-three acute ischemic stroke patients who were treated with intraarterial thrombolysis and underwent MRI within 6 hours of symptom onset were enrolled in this study. All study participants had either M1 or M2 occlusion on digital subtraction angiography before thrombolysis and underwent follow-up MRI 2-3 days after thrombolysis. Recanalization status was evaluated using the thrombolysis in myocardial infarction (TIMI) flow grade on digital subtraction angiography immediately after thrombolysis. The serial progression of the susceptibility sign on follow-up T2*-weighted imaging was compared with the MR angiographic findings. Baseline clinical parameters and clinical outcome were also reviewed. RESULTS: A positive MCA susceptibility sign on the initial T2*-weighted imaging was detected in 16 (48%) of the 33 patients. The mean TIMI grade was higher in the patients with a positive sign on imaging than in those without the sign (2.3 vs 1.0, respectively; p < 0.005). In the risk factor analysis, a history of atrial fibrillation was significantly higher in the patients with the MCA susceptibility sign than in those with negative findings for the sign (13/16 [81%] vs 4/17 [24%], respectively). In 14 of the 16 patients with the positive sign, the sign disappeared on follow-up MRI, and that finding (i.e., disappearance of the sign) was well correlated with complete recanalization on follow-up MR angiography in 12 patients. Multivariate logistic regression analysis showed that this sign was not associated with a favorable functional outcome 30 days after thrombolytic treatment. CONCLUSION: The MCA susceptibility sign can be indicative of acute thromboembolic occlusion and can be used to predict the immediate effectiveness of intraarterial thrombolysis. However, the appearance of this sign was not associated with a favorable clinical outcome after thrombolysis in our small series study.

stroke thrombolysis research PMID: 17114520 [PubMed - indexed for MEDLINE]African American women have poor long-term survival following ischemic stroke. stroke thrombolysis research related articles

African American women have poor long-term survival following ischemic stroke.

Neurology. 2006 Nov 14;67(9):1623-9

stroke thrombolysis Authors: Qureshi AI, Suri MF, Zhou J, Divani AA

OBJECTIVE: To determine racial and gender differences in long-term survival following ischemic stroke in a well-defined cohort of patients. METHODS: We analyzed the prospectively collected data from a randomized, placebo-controlled trial in patients with ischemic stroke presenting within 3 hours of symptom onset. We determined the effect of race and gender on 1-year survival ascertained by serial follow-ups using Kaplan-Meier analysis. Multivariate analysis was performed adjusting for age, initial NIH Stroke Scale (NIHSS) score, use of thrombolysis, time to randomization, stroke etiology, and other cardiovascular risk factors. RESULTS: Of the 547 patients with ischemic stroke, the 1-year survival (percentage +/- SE) for African American women (63 +/- 6%) was lower than white women (73 +/- 4%), African American men (79 +/- 4%), and white men (75 +/- 3%). Among the 209 patients younger than 65 years, the 1-year survival was prominently lower for African American women (66 +/- 8%) vs white women (87 +/- 5%), African American men (83 +/- 5%), and white men (89 +/- 3%). In the Cox proportional hazard analysis, African American women had a significantly higher rate of 1-year mortality (relative risk 2.1, 95% CI 1.2 to 3.5) after adjusting for all potential confounders except diabetes mellitus. After adjustment for diabetes mellitus, the difference became insignificant, although a 70% greater risk of 1-year mortality was still observed. CONCLUSIONS: Compared with whites and men, African American women have a lower 1-year survival following ischemic stroke.

stroke thrombolysis research PMID: 17101894 [PubMed - indexed for MEDLINE]Peripheral arterial embolism during thrombolysis for stroke. stroke thrombolysis research related articles

Peripheral arterial embolism during thrombolysis for stroke.

Neurology. 2006 Sep 26;67(6):1096-7

stroke thrombolysis Authors: Gomez-Beldarrain M, Telleria M, Garcia-Monco JC

stroke thrombolysis research PMID: 17000990 [PubMed - indexed for MEDLINE]Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38). stroke thrombolysis research related articles

Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38).

Am Heart J. 2006 Oct;152(4):627-35

stroke thrombolysis Authors: Wiviott SD, Antman EM, Gibson CM, Montalescot G, Riesmeyer J, Weerakkody G, Winters KJ, Warmke JW, McCabe CH, Braunwald E,

BACKGROUND: Dual antiplatelet therapy with aspirin and clopidogrel is standard for prevention of thrombotic complications of percutaneous coronary intervention (PCI). Prasugrel is a thienopyridine that is more potent, more rapid in onset, and more consistent in inhibition of platelets than clopidogrel. TRITON-TIMI 38 is designed to compare prasugrel with clopidogrel in moderate to high-risk patients with acute coronary syndrome (ACS). STUDY DESIGN: TRITON-TIMI 38 is a phase 3, randomized, double-blind, parallel-group, multinational, clinical trial. Approximately 13,000 patients with moderate to high-risk ACS undergoing PCI (9500 unstable angina/non-ST-segment elevation myocardial infarction [MI], 3500 ST-segment elevation MI) will be randomized to prasugrel 60 mg loading dose followed by 10 mg daily or clopidogrel 300 mg loading dose followed by 75 mg daily for up to 15 months. The primary end point is the time of the first event of cardiovascular death, MI, or stroke. Analyses will be performed first in the unstable angina/non-ST-segment elevation MI cohort and, conditionally, on the whole ACS population. Major safety end points include TIMI major and minor bleeding unrelated to coronary artery bypass graft surgery. CONCLUSIONS: TRITON-TIMI 38 is a phase 3 comparison of prasugrel versus clopidogrel in patients with moderate to high-risk ACS undergoing PCI. In addition, it is the first large-scale clinical events trial to assess whether a thienopyridine regimen that achieves a higher level of inhibition of platelet aggregation than the standard therapy results in an improvement in clinical outcomes.

stroke thrombolysis research PMID: 16996826 [PubMed - indexed for MEDLINE]Factors predicting prognosis after decompressive hemicraniectomy for hemispheric infarction. stroke thrombolysis research related articles

Factors predicting prognosis after decompressive hemicraniectomy for hemispheric infarction.

Neurology. 2006 Sep 12;67(5):891-3

stroke thrombolysis Authors: Rabinstein AA, Mueller-Kronast N, Maramattom BV, Zazulia AR, Bamlet WR, Diringer MN, Wijdicks EF

The authors reviewed 42 consecutive cases of decompressive hemicraniectomy after hemispheric ischemic stroke to assess predictors of outcome. On univariate analysis, advanced age and history of hypertension were significantly associated with unfavorable outcome, whereas thrombolysis was protective. Side of infarction, pupillary nonreactivity, degree of preoperative midline shift, and timing of surgery did not predict outcome. On multivariate analysis, older age independently predicted poor recovery (odds ratio 2.9 per 10-year increase in age).

stroke thrombolysis research PMID: 16966561 [PubMed - indexed for MEDLINE]Outcome in hyperglycemic stroke with ultrasound-augmented thrombolytic therapy. stroke thrombolysis research related articles

Outcome in hyperglycemic stroke with ultrasound-augmented thrombolytic therapy.

Neurology. 2006 Aug 22;67(4):700-2

stroke thrombolysis Authors: Martini SR, Hill MD, Alexandrov AV, Molina CA, Kent TA

Hyperglycemia independently predicts poor outcome after acute ischemic stroke. CLOTBUST (Combined Lysis Of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic tPA) demonstrated that ultrasound-augmented thrombolysis improves recanalization and 24-hour outcome in patients with acute ischemic stroke. We hypothesized that ultrasound would preferentially benefit hyperglycemic patients, and reviewed CLOTBUST with respect to admission glucose and good outcome. We found that ultrasound's benefit on 90-day outcome was primarily apparent at higher glucose levels, suggesting that ultrasound therapy may improve outcome following hyperglycemic stroke.

stroke thrombolysis research PMID: 16924029 [PubMed - indexed for MEDLINE]How well does ASPECTS predict the outcome of acute stroke treated with IV tPA? stroke thrombolysis research related articles

How well does ASPECTS predict the outcome of acute stroke treated with IV tPA?

Neurology. 2006 Aug 8;67(3):516-8

stroke thrombolysis Authors: Weir NU, Pexman JH, Hill MD, Buchan AM,

The authors measured the association of early ischemic change on CT scan, measured using the Alberta Stroke Programme Early CT score (ASPECTS), and functional outcome in 825 patients with anterior circulation stroke treated with IV thrombolysis within 3 hours of onset. ASPECTS predicted outcome in a graded fashion (linearly for ASPECTS 6 through 10; pattern ill-defined for ASPECTS 0 through 5) but discriminated individual outcomes weakly. Except perhaps when early ischemic change is extensive, clinicians should not estimate prognosis using ASPECTS alone.

stroke thrombolysis research PMID: 16894120 [PubMed - indexed for MEDLINE]Characterizing physiological heterogeneity of infarction risk in acute human ischaemic stroke using MRI. stroke thrombolysis research related articles

Characterizing physiological heterogeneity of infarction risk in acute human ischaemic stroke using MRI.

Brain. 2006 Sep;129(Pt 9):2384-93

stroke thrombolysis Authors: Wu O, Christensen S, Hjort N, Dijkhuizen RM, Kucinski T, Fiehler J, Thomalla G, Röther J, Østergaard L

Viable tissues at risk of infarction in acute stroke patients have been hypothesized to be detectable as volumetric mismatches between lesions on perfusion-weighted (PWI) and diffusion-weighted magnetic resonance imaging (DWI). Because tissue response to ischaemic injury and to therapeutic intervention is tissue- and patient-dependent, changes in infarct progression due to treatment may be better detected with voxel-based methods than with volumetric mismatches. Acute DWI and PWI were combined using a generalized linear model (GLM) to predict infarction risk on a voxel-wise basis for patients treated either with non-thrombolytic (Group 1; n = 11) or with thrombolytic therapy (Group 2; n = 27). Predicted infarction risk for both groups was evaluated in four ipsilateral regions of interest: tissue acutely abnormal on DWI (Core), tissue acutely abnormal on PWI but normal on DWI that either infarcts (Recruited) or does not (Salvaged), and tissue normal on both DWI and PWI that does not infarct (Normal) by follow-up imaging > or = 5 days. The performance of the models was significantly reduced for the thrombolysed group compared with the group receiving standard treatment, suggesting an alteration in natural progression of the ischaemic cascade. Average GLM-predicted infarction risk values in the four regions were different from one another for both groups. GLM-predicted infarction risk in Salvaged tissue was significantly higher (P = 0.02) for thrombolysed patients than for non-thrombolysed patients, suggesting that thrombolysis rescued tissue with higher infarction risk than typically measured in tissue that spontaneously recovered. The observed spatial heterogeneity of GLM-predicted infarction risk values probably reflects the varying degrees of tissue injury and salvageability that exist after stroke. MRI-based algorithms may therefore provide a more sensitive means for monitoring therapeutic effects on a voxel-wise basis.

stroke thrombolysis research PMID: 16891322 [PubMed - indexed for MEDLINE]Door to thrombolysis: ER reorganization and reduced delays to acute stroke treatment. stroke thrombolysis research related articles

Door to thrombolysis: ER reorganization and reduced delays to acute stroke treatment.

Neurology. 2006 Jul 25;67(2):334-6

stroke thrombolysis Authors: Lindsberg PJ, Häppölä O, Kallela M, Valanne L, Kuisma M, Kaste M

The authors reorganized the emergency room (ER) by moving CT to the ER and streamlining triage by prenotification by emergency medical services (EMS), which reduced in-hospital delays and enhanced access to stroke thrombolysis. CT delay dropped from 1 hour 3 minutes +/- 14 minutes in 1999 to 7 +/- 2 minutes in 2004 (p < 0.0001). Door-to-needle time dropped from 1 hour 28 minutes +/- 7 minutes to 50 +/- 3 minutes (p < 0.001), while symptom-to-needle time dropped from 2 hours 44 minutes +/- 6 minutes to 2 hours 5 minutes +/- 4 minutes (p < 0.0001). From 23 patients in 1999, thrombolysis access was increased to 100 patients in 2004 and 183 patients in 2005.

stroke thrombolysis research PMID: 16864834 [PubMed - indexed for MEDLINE]Combined IV-intra-arterial thrombolysis: a color-coded duplex pilot study. stroke thrombolysis research related articles

Combined IV-intra-arterial thrombolysis: a color-coded duplex pilot study.

Neurology. 2006 Jul 25;67(2):324-6

stroke thrombolysis Authors: Perren F, Loulidi J, Graves R, Yilmaz H, Rüfenacht D, Landis T, Sztajzel R

The authors compared the transcranial color-coded duplex pattern of the middle cerebral arteries (MCAs) before and after IV and combined IV-intra-arterial (IV-IA) thrombolysis in consecutive first-ever stroke patients. Patients receiving combined IV-IA thrombolysis showed greater improvement in flow signal and higher incidence of complete MCA recanalization vs those receiving IV thrombolysis, especially when the MCA was occluded or had only minimal flow.

stroke thrombolysis research PMID: 16864830 [PubMed - indexed for MEDLINE]Stroke thrombolysis: slow progress. stroke thrombolysis research related articles

Stroke thrombolysis: slow progress.

Circulation. 2006 Jul 18;114(3):187-90

stroke thrombolysis Authors: Caplan LR

stroke thrombolysis research PMID: 16847163 [PubMed - indexed for MEDLINE]Rheolytic thrombectomy with percutaneous coronary intervention for infarct size reduction in acute myocardial infarction: 30-day results from a multicenter randomized study. stroke thrombolysis research related articles

Rheolytic thrombectomy with percutaneous coronary intervention for infarct size reduction in acute myocardial infarction: 30-day results from a multicenter randomized study.

J Am Coll Cardiol. 2006 Jul 18;48(2):244-52

stroke thrombolysis Authors: Ali A, Cox D, Dib N, Brodie B, Berman D, Gupta N, Browne K, Iwaoka R, Azrin M, Stapleton D, Setum C, Popma J,

OBJECTIVES: The goal of this work was to determine whether rheolytic thrombectomy (RT) as an adjunct to primary percutaneous coronary intervention (PCI) reduces infarction size and improves myocardial perfusion during treatment of ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Primary PCI for STEMI achieves brisk epicardial flow in most patients, but myocardial perfusion often remains suboptimal. Distal embolization of thrombus during treatment may be a contributing factor. METHODS: This prospective, multicenter trial enrolled 480 patients presenting within 12 h of symptom onset and randomized to treatment with RT as an adjunct to PCI (n = 240) or to PCI alone (n = 240). Visible thrombus was not required. The primary end point was infarct size measured by sestamibi imaging at 14 to 28 days. Secondary end points included final Thrombolysis In Myocardial Infarction (TIMI) flow grade, tissue myocardial perfusion (TMP) blush, ST-segment resolution, and major adverse cardiac events (MACE), defined as the occurrence of death, new Q-wave myocardial infarction, emergent coronary artery bypass grafting, target lesion revascularization, stroke, or stent thrombosis at 30 days. RESULTS: Final infarct size was higher in the adjunct RT group compared with PCI alone (9.8 +/- 10.9% vs. 12.5 +/- 12.13%; p = 0.03). Final TIMI flow grade 3 was lower in the adjunct RT group (91.8% vs. 97.0% in the PCI alone group; p < 0.02), although fewer patients had baseline TIMI flow grade 3 in the adjunct RT group (44% vs. 63% in the PCI alone group; p < 0.05). There were no significant differences in TMP blush scores or ST-segment resolution. Thirty-day MACE was higher in the adjunct RT group (6.7% vs. 1.7% in the PCI alone group; p = 0.01), a difference primarily driven by very low mortality rate in patients treated with PCI alone (0.8% vs. 4.6% in patients treated with adjunct RT; p = 0.02). CONCLUSIONS: Despite effective thrombus removal, RT with primary PCI did not reduce infarct size or improve TIMI flow grade, TMP blush, ST-segment resolution, or 30-day MACE.

stroke thrombolysis research PMID: 16843170 [PubMed - indexed for MEDLINE]Stroke thrombolysis in the elderly: risk or benefit? stroke thrombolysis research related articles

Stroke thrombolysis in the elderly: risk or benefit?

Neurology. 2006 Jul 11;67(1):183-4; author reply 183-4

stroke thrombolysis Authors: Beletsky V, Hachinski V

stroke thrombolysis research PMID: 16832114 [PubMed - indexed for MEDLINE]Continuous assessment of electrical epileptic activity in acute stroke. stroke thrombolysis research related articles

Continuous assessment of electrical epileptic activity in acute stroke.

Neurology. 2006 Jul 11;67(1):99-104

stroke thrombolysis Authors: Carrera E, Michel P, Despland PA, Maeder-Ingvar M, Ruffieux C, Debatisse D, Ghika J, Devuyst G, Bogousslavsky J

OBJECTIVE: To determine the incidence and risk factors of electrical seizures and other electrical epileptic activity using continuous EEG (cEEG) in patients with acute stroke. METHODS: One hundred consecutive patients with acute stroke admitted to our stroke unit underwent cEEG using 10 electrodes. In addition to electrical seizures, repetitive focal sharp waves (RSHWs), repetitive focal spikes (RSPs), and periodic lateralized epileptic discharges (PLEDs) were recorded. RESULTS: In the 100 patients, cEEG was recorded for a mean duration of 17 hours 34 minutes (range 1 hour 12 minutes to 37 hours 10 minutes). Epileptic activity occurred in 17 patients and consisted of RSHWs in seven, RSPs in seven, and PLEDs in three. Electrical seizures occurred in two patients. On univariate Cox regression analysis, predictors for electrical epileptic activity were stroke severity (high score on the National Institutes of Health Stroke Scale) (hazard ratio [HR] 1.12; p = 0.002), cortical involvement (HR 5.71; p = 0.021), and thrombolysis (HR 3.27; p = 0.040). Age, sex, stroke type, use of EEG-modifying medication, and cardiovascular risk factors were not predictors of electrical epileptic activity. On multivariate analysis, stroke severity was the only independent predictor (HR 1.09; p = 0.016). CONCLUSION: In patients with acute stroke, electrical epileptic activity occurs more frequently than previously suspected.

stroke thrombolysis research PMID: 16832085 [PubMed - indexed for MEDLINE]Unanswered questions for management of acute coronary syndrome: risk stratification of patients with minimal disease or normal findings on coronary angiography. stroke thrombolysis research related articles

Unanswered questions for management of acute coronary syndrome: risk stratification of patients with minimal disease or normal findings on coronary angiography.

Arch Intern Med. 2006 Jul 10;166(13):1391-5

stroke thrombolysis Authors: Bugiardini R, Manfrini O, De Ferrari GM

BACKGROUND: The prognostic implication of chest pain associated with normal or near-normal findings on angiography is still unknown. We explored outcomes and methods of risk stratification in patients with nonobstructive coronary artery disease in the setting of non-ST-segment elevation acute coronary syndromes. METHODS: Data were pooled from 3 Thrombolysis in Myocardial Infarction (TIMI) trials (TIMI 11B, TIMI 16, and TIMI 22). Angiographic data were available on 7656 patients with non-ST-segment elevation acute coronary syndromes. The primary end point of this analysis was the composite of the rates of death, myocardial infarction, unstable angina requiring rehospitalization, revascularization, and stroke at 1-year follow-up. Outcomes were evaluated by mean of the TIMI risk score for developing at least 1 component of the primary end point. RESULTS: Angiographic findings showed that 710 (9.1%) of 7656 patients had nonobstructive coronary artery disease; 48.7% of these had normal coronary arteries (0% stenosis), and 51.3% had mild coronary artery disease (>0% to <50% stenosis). A primary end-point event occurred in 101 patients (12.1%). It is noteworthy that a 2% event rate of deaths and myocardial infarctions had occurred in these patients at the 1-year follow-up. Event rates of death and myocardial infarction increased significantly as the TIMI risk score increased from 0.6% for a score of 1 to 4.0% for a score greater than 4. CONCLUSIONS: Patients with non-ST-segment elevation acute coronary syndromes with nonobstructive coronary artery disease detected by angiography have a substantial risk of subsequent coronary events within 1 year. The risk is not univariately high, and the TIMI risk score helps to reveal patients at high risk.

stroke thrombolysis research PMID: 16832004 [PubMed - indexed for MEDLINE]Early recurrent ischemic stroke in stroke patients undergoing intravenous thrombolysis.

Early recurrent ischemic stroke in stroke patients undergoing intravenous thrombolysis.

Circulation. 2006 Jul 18;114(3):237-41

stroke thrombolysis Authors: Georgiadis D, Engelter S, Tettenborn B, Hungerbühler H, Luethy R, Müller F, Arnold M, Giambarba C, Baumann CR, von Büdingen HC, Lyrer P, Baumgartner RW

BACKGROUND: We assessed the incidence of early recurrent ischemic stroke in stroke patients treated with intravenous tissue-type plasminogen activator (tPA) and the temporal pattern of its occurrence compared with symptomatic intracranial hemorrhage (ICH). METHODS AND RESULTS: Prospectively collected, population-based data for 341 consecutive acute stroke patients (62% men; mean age, 66 years) treated with tPA according to the National Institute of Neurological Disorders and Stroke study protocol at 8 medical centers in Switzerland (3 academic and 5 community) between January 2001 and November 2004 were retrospectively analyzed. The primary outcome measure was neurological deterioration > or = 4 points on the National Institutes of Health Stroke Scale occurring within 24 hours of tPA treatment and caused either by recurrent ischemic stroke (defined as the occurrence of new neurological symptoms suggesting involvement of initially unaffected vascular territories and evidence of corresponding ischemic lesions on cranial computed tomography scans, in the absence of ICH) or by ICH. Early recurrent ischemic stroke was diagnosed in 2 patients (0.59%; 95% confidence interval, 0.07% to 2.10%) and symptomatic ICH in 15 patients (4.40%; 95% confidence interval, 2.48% to 7.15%). Both recurrent ischemic strokes occurred during thrombolysis, whereas symptomatic ICHs occurred 2 to 22 hours after termination of tPA infusion. CONCLUSIONS: Recurrent ischemic stroke is a rare cause of early neurological deterioration in acute stroke patients undergoing intravenous thrombolysis, with a different temporal pattern compared with that of symptomatic ICH.

stroke thrombolysis research PMID: 16831985 [PubMed - indexed for MEDLINE]Argatroban: update. stroke thrombolysis research related articles

Argatroban: update.

Am Heart J. 2006 Jun;151(6):1131-8

stroke thrombolysis Authors: Yeh RW, Jang IK

Unfractionated heparin has historically been used as the anticoagulant of choice in the management of a number of thrombotic diseases. Recognition of the limitations of heparin has led to the development of a newer class of anticoagulants, the direct thrombin inhibitors. Argatroban is a synthetic small molecule that selectively inhibits thrombin at its active site. In preclinical studies, argatroban has been shown to be more effective than heparin in preventing arterial thrombosis and in promoting vessel patency in conjunction with thrombolysis in a number of animal models. In clinical trials, argatroban has been shown to be as effective as heparin in the management of ST-segment elevation myocardial infarction in conjunction with thrombolysis. It has been shown to be an effective anticoagulant in patients undergoing percutaneous coronary interventions. In patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia complicated by thrombosis, argatroban significantly decreases the risk of thrombotic events. Small studies have demonstrated a potential role for its use in ischemic stroke and hemodialysis. Additional studies are warranted to confirm argatroban's efficacy in a wide variety of clinical settings.

stroke thrombolysis research PMID: 16781211 [PubMed - indexed for MEDLINE]Influence of gender on outcomes after intra-arterial thrombolysis for acute ischemic stroke. stroke thrombolysis research related articles

Influence of gender on outcomes after intra-arterial thrombolysis for acute ischemic stroke.

Neurology. 2006 Jun 13;66(11):1745-6

stroke thrombolysis Authors: Shah SH, Liebeskind DS, Saver JL, Starkman S, Vinuela F, Duckwiler G, Jahan R, Kim D, Sanossian N, Vespa P, Ovbiagele B

Recent data suggest that women obtain greater benefit than men from IV fibrinolysis for acute ischemic stroke. It is unknown whether this gender-thrombolysis advantage extends to those treated with intra-arterial (IA) thrombolysis. The authors evaluated the independent effect of gender among ischemic stroke patients treated with IA fibrinolysis and found no differences in short-term clinical and angiographic outcomes between men and women who received IA thrombolysis for acute ischemic stroke.

stroke thrombolysis research PMID: 16769954 [PubMed - indexed for MEDLINE]Mortality of stroke patients treated with thrombolysis: analysis of nationwide inpatient sample.

Mortality of stroke patients treated with thrombolysis: analysis of nationwide inpatient sample.

Neurology. 2006 Jun 13;66(11):1742-4

stroke thrombolysis Authors: Dubinsky R, Lai SM

The authors performed a retrospective cohort comparison using the Nationwide Inpatient Sample for 1999 through 2002 of acute ischemic stroke admissions. Mortality was compared based on the use of thrombolysis. Hospital mortality was significantly greater for the thrombolysis cohort (10.1% vs 5.8%) as was the rate of secondary intracranial hemorrhage (4.2% vs 0.4%). US community experience in the use of thrombolysis has higher rates of complications and mortality than in controlled clinical trials.

stroke thrombolysis research PMID: 16769953 [PubMed - indexed for MEDLINE]Ischemic strokes after cardiac catheterization: opportune thrombolysis candidates? stroke thrombolysis research related articles

Ischemic strokes after cardiac catheterization: opportune thrombolysis candidates?

Arch Neurol. 2006 Jun;63(6):817-21

stroke thrombolysis Authors: Khatri P, Kasner SE

Stroke is an important complication after cardiac catheterization procedures, resulting in death and disability for thousands of patients each year. Common risk factors include advanced age, vascular comorbidities, and more complicated and invasive procedures. Several lines of evidence suggest that these strokes are embolic, from either dislodgement of a clot or atheromatous debris off the aortic arch or from thrombus formation on the tip of a guide catheter. These strokes are likely amenable to thrombolysis, although the current literature regarding the use of thrombolysis in this setting is limited to case reports and series. Whether thrombolysis is safe and efficacious remains to be determined, but the existing evidence seems favorable for individual circumstances.

stroke thrombolysis research PMID: 16769862 [PubMed - indexed for MEDLINE]Association between tPA therapy and raised early matrix metalloproteinase-9 in acute stroke. stroke thrombolysis research related articles

Association between tPA therapy and raised early matrix metalloproteinase-9 in acute stroke.

Neurology. 2006 May 23;66(10):1550-5

stroke thrombolysis Authors: Ning M, Furie KL, Koroshetz WJ, Lee H, Barron M, Lederer M, Wang X, Zhu M, Sorensen AG, Lo EH, Kelly PJ

BACKGROUND: Matrix metalloproteinase-9 (MMP9) is expressed in acute ischemic stroke and up-regulated by tissue plasminogen activator (tPA) in animal models. The authors investigated plasma MMP9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase (TIMP1), in tPA-treated and -untreated stroke patients. METHODS: Nonstroke control subjects and consecutive ischemic stroke patients presenting within 8 hours of onset were enrolled. Blood was sampled within 8 hours and at 24 hours, 2 to 5 days and 4 to 6 weeks. MMP9 and TIMP1 were analyzed by ELISA and gel zymography. RESULTS: Fifty-two cases (26 tPA treated, 26 tPA untreated) and 27 nonstroke control subjects were enrolled. Hyperacute MMP9 was elevated in tPA-treated vs tPA-untreated patients (medians 43 vs 28 ng/mL; p = 0.01). tPA therapy independently predicted hyperacute MMP9 after adjustment for stroke severity, volume, and hemorrhagic transformation (p = 0.01). There was a trend toward lower hyperacute TIMP1 levels in tPA-treated vs tPA-untreated patients (p = 0.06). Hyperacute MMP9 was correlated to poor 3-month modified Rankin Scale outcome (r = 0.58, p = 0.0005). CONCLUSION: Tissue plasminogen activator independently predicted plasma matrix metalloproteinase-9 (MMP9) in the first 8 hours after human ischemic stroke. As MMP9 may be an important mediator of hemorrhagic transformation, alternative thrombolytic agents or therapeutic MMP9 inhibition may increase the safety profile of acute stroke thrombolysis.

stroke thrombolysis research PMID: 16717217 [PubMed - indexed for MEDLINE]

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