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Michael Chopp - One of the best experts on this subject based on the ideXlab platform.

  • prospective double blinded comparative assessment of the pharmacological activity of cerebrolysin and distinct peptide preparations for the treatment of Embolic Stroke
    Journal of the Neurological Sciences, 2019
    Co-Authors: Li Zhang, Michael Chopp, Yi Zhang, Talan Zhang, Chunyang Wang, Zhenggang Zhang
    Abstract:

    Abstract Background Our previous work in acute ischemic Stroke and TBI models focused on efficacy and pharmacological parameters of Cerebrolysin®. In this prospective, randomized, blinded, placebo-controlled study we compared efficacy of neuropeptide preparations with putative neurotrophic potential to the reference product Cerebrolysin® by assessing functional outcome and lesion volumes after Embolic Stroke in a rodent model. Methods Male Wistar rats were subjected to Embolic right middle cerebral artery occlusion and were treated with: 1) Cognistar® (Cerebroprotein Hydrolysate) 2.5 ml/kg, 2) Cerebrolysat® 2.5 ml/kg, 3) Cortexin® 1.7 mg/kg, 4) Cerebrolysin® 2.5 ml/kg, or 5) 1 ml of saline according to a pre-generated randomization plan. Dosages were defined according to the packet leaflet of the corresponding preparation and were adapted to the animal model as previously described. All enrolled rats received intraperitoneal injections once daily for 10 consecutive days, starting 4 h after occlusion. Functional outcome was assessed once weekly over four weeks by using a battery of behavioral tests. Infarct volume was measured four weeks after occlusion. Generalized Estimation Equations (GEE) was performed to study the treatment effect on overall functional recovery at day 28 (primary outcome), compared to saline controls. Results Similar functional outcome was observed for saline control, Cognistar®, Cerebrolysat® and Cortexin®; in contrast, a significantly improved neurological outcome was observed with Cerebrolysin® treatment in comparison to saline as well as to the comparator drug treatment (p  Conclusion Among all tested neuropeptide preparations, Cerebrolysin® was the only agent that was associated with a significant improvement of neurological outcome after Stroke.

  • cerebral tissue repair and atrophy after Embolic Stroke in rat a magnetic resonance imaging study of erythropoietin therapy
    Journal of Neuroscience Research, 2010
    Co-Authors: Guangliang Ding, Zhenggang Zhang, Michael Chopp, Li Zhang, Quan Jiang, Ying Wang, Swayamprava Panda, James R Ewing
    Abstract:

    Using magnetic resonance imaging (MRI) protocols of T2-, T2*-, diffusion- and susceptibility-weighted imaging (T2WI, T2*WI, DWI, and SWI, respectively) with a 7T system, we tested the hypothesis that treatment of Embolic Stroke with erythropoietin (EPO) initiated at 24 hr and administered daily for 7 days after Stroke onset has benefit in repairing ischemic cerebral tissue. Adult Wistar rats were subjected to Embolic Stroke by means of middle cerebral artery occlusion (MCAO) and were randomly assigned to a treatment (n = 11) or a control (n = 11) group. The treated group was given EPO intraperitoneally at a dose of 5,000 IU/kg daily for 7 days starting 24 hr after MCAO. Controls were given an equal volume of saline. MRI was performed at 24 hr and then weekly for 6 weeks. MRI and histological measurements were compared between groups. Serial T2WI demonstrated that expansion of the ipsilateral ventricle was significantly reduced in the EPO-treated rats. The volume ratio of ipsilateral parenchymal tissue relative to the contralateral hemisphere was significantly increased after EPO treatment compared with control animals, indicating that EPO significantly reduces atrophy of the ipsilateral hemisphere, although no significant differences in ischemic lesion volume were observed between the two groups. Angiogenesis and white matter remodeling were significantly increased and occurred earlier in EPO-treated animals than in the controls, as evident from T2*WI and diffusion anisotropy maps, respectively. These data indicate that EPO treatment initiated 24 hr postStroke promotes angiogenesis and axonal remodeling in the ischemic boundary, which may potentially reduce atrophy of the ipsilateral hemisphere. © 2010 Wiley-Liss, Inc.

  • thymosin β4 improves functional neurological outcome in a rat model of Embolic Stroke
    Neuroscience, 2010
    Co-Authors: Daniel C Morris, Li Zhang, Michael Chopp, Zhenggang Zhang
    Abstract:

    Thymosin β4 (Tβ4) is a developmentally expressed 43-amino acid peptide that was originally isolated from thymic extract and exists in numerous tissues and isoforms (Goldstein et al., 1966). Tβ4 inhibits organization of the actin-cytoskeleton by sequestration of G-actin monomers thereby enabling cells to migrate (Goldstein et al., 2005). Additionally, Tβ4 may regulate nuclear actin thereby influencing chromatin remodeling and ultimately gene expression (Huff et al., 2004). Tβ4 has multiple biological functions in addition to its actin binding properties. Tβ4 is an angiogenic promoting molecule which stimulates endothelial cell migration and tubule formation (Malinda et al., 1999, Smart et al., 2007). Tβ4 also promotes healing properties in both wounds and corneal injury by increasing cell migration and reducing inflammation. (Malinda et al., 1999, Sosne et al., 2002). Clinically, Tβ4 promotes wound healing and is being tested in a clinical trial of wound healing (Guarnera et al., 2007). Tβ4 promotes cardiomyocyte survival and improves cardiac function after myocardial infarction (MI) in experimental adult mice (Bock-Marquette et al., 2004). Tβ4 administration reduces left ventricular scar volume and promotes cardiomyocyte cell survival within 24 hours of coronary ligation. Tβ4 activation of Akt has been proposed as a potential mechanism that increases cell survival after acute MI. Hinkel et al, demonstrated in a pig MI model that downregulation of Tβ4 in embryonic endothelial progenitor cells used to treat experimental MI confers a loss of cardiomyocyte survival, increases infarct volume and reduces left ventricle function (Hinkel et al., 2008). Furthermore, Smart et al, demonstrated that epicardial progenitor cells isolated from wild type adult hearts differentiate into smooth muscle and endothelial cells when cultured in the presence of Tβ4 (Smart et al., 2007). Collectively, Tβ4 may improve cardiac function by promoting cardiomyocyte survival and may stimulate epicardial progenitor cells to differentiate into smooth muscle and endothelial cell types to repair damaged myocardium. Over the past two decades, research on treatment of Stroke has focused on neuroprotection and revascularization strategies. The only successful clinical trial that has resulted from this research is the use of tissue plasminogen activator (rt-PA) within 4.5 hours of symptom onset (The NINDS rt-PA Stroke Study Group 1995, Hacke et al., 2008). Use of rt-PA has been limited because of its narrow time-dependent treatment window as most Stroke patients present to the Emergency Department well beyond six hours of symptom onset (California Acute Stroke Pilot Registry (CASPR) Investigators, 2005, Kleindorfer et al., 2007) Moreover, use of rt-PA is complicated by a 6.4% symptomatic intracerbral hemmorhage (ICH) rate which has caused considerable controversy regarding its practical use, particularly amongst Emergency physicians. The restriction on time and potential adverse effects have limited the use of rt-PA to approximately 3% of Stroke patients (California Acute Stroke Pilot Registry (CASPR) Investigators, 2005, Kleindorfer et al., 2009). Thus, it is imperative to develop therapies for ischemic Stroke designed specifically to reduce neurological deficits, which can be employed to treat the vast majority of patients. Tβ4 is expressed in both the developing and adult brain (Carpintero et al., 1999, Gomez-Marquez and Anadon, 2002). Specifically, Tβ4 is localized in growing neurites of neurons (van Kesteren et al., 2006, Yang et al., 2008). In many disease states such as focal ischemia and Huntington’s disease, gene expression of Tβ4 is upregulated (Vartiainen et al., 1996, Sapp et al., 2001). Moreover, Tβ4 is upregulated 12 hours to 7 days after focal ischemia (Vartiainen et al., 1996). Since actin dynamics contribute to cell migration and synaptogenesis, we speculate that administration of Tβ4 could enhance recovery. Using a rat model of Embolic Stroke, we tested the hypothesis that treatment with Tβ4 improves neurological functional outcome when administered 24 hours after onset of ischemia.

  • atorvastatin extends the therapeutic window for tpa to 6 h after the onset of Embolic Stroke in rats
    Journal of Cerebral Blood Flow and Metabolism, 2009
    Co-Authors: Li Zhang, Michael Chopp, Longfei Jia, Yisheng Cui, Zhenggang Zhang
    Abstract:

    We investigated the neuroprotective effect of atorvastatin in combination with delayed thrombolytic therapy in a rat model of Embolic Stroke. Rats subjected to Embolic middle cerebral artery (MCA) occlusion were treated with atorvastatin at 4 h, followed by tissue plasminogen activator (tPA) at 6 or 8 h after Stroke. The combination of atorvastatin at 4 h and tPA at 6 h significantly decreased the size of the embolus at the origin of the MCA, improved microvascular patency, and reduced infarct volume, but did not increase the incidence of hemorrhagic transformation compared with vehicle-treated control animals. However, monotherapy with tPA at 6 h increased the incidence of hemorrhagic transformation and failed to reduce infarct volume compared with the control group. In addition, adjuvant treatment with atorvastatin at 4 h and with tPA at 6 h reduced tPA-induced upregulation of protease-activated receptor-1, intercellular adhesion molecule-1, and matrix metalloproteinase-9, and concomitantly reduced cerebral microvascular platelet, neutrophil, and fibrin deposition compared with rats treated with tPA alone at 6 h. In conclusion, a combination of atorvastatin and tPA extended the therapeutic window for Stroke to 6 h without increasing the incidence of hemorrhagic transformation. Atorvastatin blocked delayed tPA-potentiated adverse cerebral vascular events, which likely contributes to the neuroprotective effect of the combination therapy.

  • tadalafil a long acting type 5 phosphodiesterase isoenzyme inhibitor improves neurological functional recovery in a rat model of Embolic Stroke
    Brain Research, 2006
    Co-Authors: Li Zhang, Zhenggang Zhang, Rui Lan Zhang, Margot C Lapointe, Brian Silver, Michael Chopp
    Abstract:

    Sildenafil, a type 5 phosphodiesterase isoenzyme (PDE5) inhibitor with a short half-life, increases brain cyclic guanosine monophosphate (cGMP) levels and improves neurological functional recovery when administered after Stroke. In the present study, we investigated the effects of tadalafil (Cialis), a long acting PDE5 inhibitor, on brain cGMP levels, neurogenesis, angiogenesis, and neurological function during Stroke recovery in a rat model of Embolic Stroke. Male Wistar rats (n=28) were subjected to Embolic middle cerebral artery (MCA) occlusion. Tadalafil was orally administered every 48 h at a dose of 2 mg/kg or 10 mg/kg for 6 consecutive days starting 24 h after Stroke onset. Control animals received the equivalent volume of saline at the same time points. For mitotic labeling, bromodeoxyuridine (BrdU, 100 mg/kg) was administered twice a day at 5, 6, and 7 days after Stroke. ELISA assays were performed to evaluate the specificity of the effect of tadalafil on cGMP. Treatment with tadalafil at a dose of 2 or 10 mg/kg significantly improved neurological functional recovery compared with saline-treated rats. In addition, tadalafil treatment increased cerebral vascular density and the percentage of BrdU-positive endothelial cells around the ischemic boundary compared with saline-treated rats. Moreover, tadalafil-treated rats showed greater ipsilateral SVZ cell proliferation than saline-treated rats. However, treatment with tadalafil did not reduce infarct volume when compared to the saline group. Tadalafil selectively increased cGMP but not cyclic adenosine monophosphate (cAMP) in brain. Our data demonstrate that treatment of ischemic Stroke with tadalafil improved functional recovery, which was associated with increases of brain cGMP levels and enhancement of angiogenesis and neurogenesis.

Hanschristoph Diener - One of the best experts on this subject based on the ideXlab platform.

  • dabigatran or aspirin after Embolic Stroke of undetermined source in patients with patent foramen ovale results from re spect esus
    Stroke, 2021
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Aurauma Chutinet, Donald J Easton, Eva Kleine, Lars Marquardt, Juliane Meyerhoff, Andrea Zini, Ralph L Sacco
    Abstract:

    Background and Purpose: Patent foramen ovale (PFO) may increase the risk of Embolic Stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets...

  • antithrombotic treatment of Embolic Stroke of undetermined source re spect esus elderly and renally impaired subgroups
    Stroke, 2020
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Martina Brueckmann, Richard A Bernstein, Donald J Easton, Ralph L Sacco, Michal Bar, Michael Brainin, Lisa Cronin
    Abstract:

    Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent Stroke in patients with Embolic Stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent Stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent Stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent Stroke in patients with Embolic Stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent Stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction P=0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction P=0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent Stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with Embolic Stroke of undetermined source. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.

  • major bleeding in patients with Embolic Stroke of undetermined source treated with dabigatran versus acetylsalicylic acid re spect esus trial
    Journal of the American College of Cardiology, 2019
    Co-Authors: Christopher B Granger, Hanschristoph Diener, Ralph Sacco, J Easton, Lisa Cronin, Mandy Frasdorf, Claudia Grauer, Martina Brueckmann
    Abstract:

    RE-SPECT ESUS™ offers an opportunity to evaluate factors associated with bleeding risk in patients with Embolic Stroke of unknown source (ESUS) treated with dabigatran vs acetylsalicylic acid (ASA). RE-SPECT ESUS was a randomized, controlled trial (570 centers in 42 countries). Patients with ESUS

  • secondary Stroke prevention in cryptogenic Stroke and Embolic Stroke of undetermined source esus
    Current Neurology and Neuroscience Reports, 2017
    Co-Authors: Hanschristoph Diener, Richard A Bernstein, Robert G Hart
    Abstract:

    The purpose of the study was to review the literature on cryptogenic Stroke and Embolic Stroke of undetermined Stroke (ESUS). Cryptogenic Stroke according to TOAST criteria is a Stroke which is not due to cardiogenic embolism, small vessel disease with lacunes or large vessel disease of brain supplying arteries. In the context of secondary Stroke prevention studies, cryptogenic Stroke is not operationally defined. The new concept of “Embolic Stroke of undetermined source” (ESUS) provides an operational definition. ESUS is diagnosed as a non-lacunar Stroke on cerebral imaging and exclusion of large vessel atherosclerosis by CTA, MRA or ultrasound. Cardiogenic embolism is made less likely by ECG monitoring and echocardiography. At present, aspirin is used for secondary Stroke prevention in patients with cryptogenic Stroke. Based on the construct that ESUS might be caused by undetected atrial fibrillation or other Embolic mechanisms, ongoing randomised secondary Stroke prevention trials are comparing non-vitamin K oral anticoagulants (NOACs) with aspirin.

  • design of randomized double blind evaluation in secondary Stroke prevention comparing the efficacy and safety of the oral thrombin inhibitor dabigatran etexilate vs acetylsalicylic acid in patients with Embolic Stroke of undetermined source re spect
    International Journal of Stroke, 2015
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Lisa Cronin, Martina Brueckmann, Donald J Easton, Christine Duffy, Daniel Cotton, Ralph L Sacco
    Abstract:

    RationaleCryptogenic ischemic Strokes constitute 20–30% of ischemic Strokes, the majority of which are Embolic Strokes of undetermined source. The standard preventive treatment in these patients is usually acetylsalicylic acid.AimThe Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) is designed to determine whether the oral thrombin inhibitor dabigatran, taken within three-months after Embolic Stroke of undetermined source, is superior to acetylsalicylic acid for prevention of recurrent Stroke and to characterize the safety of dabigatran in this setting.DesignProspective, randomized, double-blind, multicenter trial in approximately 6000 patients and 550 centers with Embolic Stroke of undetermined source. Subjects are randomized to dabigatran or acetylsalicylic acid and treated for an expected minimum of six-m...

Martina Brueckmann - One of the best experts on this subject based on the ideXlab platform.

  • dabigatran or aspirin in east asian patients with Embolic Stroke of undetermined source re spect esus subgroup analysis
    Stroke, 2021
    Co-Authors: Shinichiro Uchiyama, Claudia Grauer, Martina Brueckmann, Kazunori Toyoda, Byungchul Lee, Chiawei Liou, Lawrence Ka Sing Wong, Atsushi Taniguchi, Yasuhisa Urano, Donald J Easton
    Abstract:

    Background and Purpose: We assessed the outcomes of dabigatran versus aspirin in a prespecified subgroup analysis of East Asian patients with Embolic Stroke of undetermined source in the RE-SPECT E...

  • antithrombotic treatment of Embolic Stroke of undetermined source re spect esus elderly and renally impaired subgroups
    Stroke, 2020
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Martina Brueckmann, Richard A Bernstein, Donald J Easton, Ralph L Sacco, Michal Bar, Michael Brainin, Lisa Cronin
    Abstract:

    Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent Stroke in patients with Embolic Stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent Stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent Stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent Stroke in patients with Embolic Stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent Stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction P=0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction P=0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent Stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with Embolic Stroke of undetermined source. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.

  • major bleeding in patients with Embolic Stroke of undetermined source treated with dabigatran versus acetylsalicylic acid re spect esus trial
    Journal of the American College of Cardiology, 2019
    Co-Authors: Christopher B Granger, Hanschristoph Diener, Ralph Sacco, J Easton, Lisa Cronin, Mandy Frasdorf, Claudia Grauer, Martina Brueckmann
    Abstract:

    RE-SPECT ESUS™ offers an opportunity to evaluate factors associated with bleeding risk in patients with Embolic Stroke of unknown source (ESUS) treated with dabigatran vs acetylsalicylic acid (ASA). RE-SPECT ESUS was a randomized, controlled trial (570 centers in 42 countries). Patients with ESUS

  • design of randomized double blind evaluation in secondary Stroke prevention comparing the efficacy and safety of the oral thrombin inhibitor dabigatran etexilate vs acetylsalicylic acid in patients with Embolic Stroke of undetermined source re spect
    International Journal of Stroke, 2015
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Lisa Cronin, Martina Brueckmann, Donald J Easton, Christine Duffy, Daniel Cotton, Ralph L Sacco
    Abstract:

    RationaleCryptogenic ischemic Strokes constitute 20–30% of ischemic Strokes, the majority of which are Embolic Strokes of undetermined source. The standard preventive treatment in these patients is usually acetylsalicylic acid.AimThe Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) is designed to determine whether the oral thrombin inhibitor dabigatran, taken within three-months after Embolic Stroke of undetermined source, is superior to acetylsalicylic acid for prevention of recurrent Stroke and to characterize the safety of dabigatran in this setting.DesignProspective, randomized, double-blind, multicenter trial in approximately 6000 patients and 550 centers with Embolic Stroke of undetermined source. Subjects are randomized to dabigatran or acetylsalicylic acid and treated for an expected minimum of six-m...

  • design of randomized double blind evaluation in secondary Stroke prevention comparing the efficacy and safety of the oral thrombin inhibitor dabigatran etexilate vs acetylsalicylic acid in patients with Embolic Stroke of undetermined source re spect
    International Journal of Stroke, 2015
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Lisa Cronin, Martina Brueckmann, Donald J Easton, Christine Duffy, Daniel Cotton, Ralph L Sacco
    Abstract:

    RationaleCryptogenic ischemic Strokes constitute 20–30% of ischemic Strokes, the majority of which are Embolic Strokes of undetermined source. The standard preventive treatment in these patients is usually acetylsalicylic acid.AimThe Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) is designed to determine whether the oral thrombin inhibitor dabigatran, taken within three-months after Embolic Stroke of undetermined source, is superior to acetylsalicylic acid for prevention of recurrent Stroke and to characterize the safety of dabigatran in this setting.DesignProspective, randomized, double-blind, multicenter trial in approximately 6000 patients and 550 centers with Embolic Stroke of undetermined source. Subjects are randomized to dabigatran or acetylsalicylic acid and treated for an expected minimum of six-m...

Lisa Cronin - One of the best experts on this subject based on the ideXlab platform.

  • dabigatran vs aspirin for secondary prevention after Embolic Stroke of undetermined source japanese subanalysis of the re spect esus randomized controlled trial
    Circulation, 2020
    Co-Authors: Kazunori Toyoda, Shinichiro Uchiyama, Atsushi Taniguchi, Yasuhisa Urano, Yasushi Hagihara, Takahiro Kuwashiro, Takahisa Mori, Kenji Kamiyama, Kenma Nozaki, Lisa Cronin
    Abstract:

    BACKGROUND The international Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the EfficaCy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate versus Acetylsalicylic Acid in Patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) trial did not demonstrate superiority of dabigatran over aspirin for reduction of recurrent Strokes in patients with Embolic Strokes of undetermined source (ESUS). Based on pre-defined subanalyses, the safety and efficacy of dabigatran vs. aspirin in Japanese patients was assessed.Methods and Results:ESUS patients were randomized to receive either dabigatran (150 or 110 mg twice daily) or aspirin (100 mg once daily). Of 5,390 patients randomized, 594 were Japanese. Most Japanese patients (99.8%) underwent brain magnetic resonance imaging for trial screening, compared to 76.8% of non-Japanese (P<0.0001). In the Japanese cohort, over a 19.4-month median follow-up period, recurrent Stroke as the primary outcome occurred in 20/294 patients (4.3%/year) in the dabigatran group and 38/300 (8.3%/year) in the aspirin group (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.32-0.94). Major bleeding occurred in 12 patients (2.5%/year) and 17 patients (3.5%/year), respectively (HR, 0.72; 95% CI, 0.34-1.52). In contrast, in the non-Japanese cohort, recurrent Stroke occurred in 4.1%/year and 4.3%/year, respectively, showing no apparent difference in recurrent Stroke for dabigatran vs. aspirin (HR, 0.91; 95% CI, 0.74-1.14). The P-interaction for treatment and region did not reach statistical significance (P=0.09). CONCLUSIONS Dabigatran was putatively associated with a lower relative risk of recurrent Stroke compared with aspirin in Japanese ESUS patients.

  • antithrombotic treatment of Embolic Stroke of undetermined source re spect esus elderly and renally impaired subgroups
    Stroke, 2020
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Martina Brueckmann, Richard A Bernstein, Donald J Easton, Ralph L Sacco, Michal Bar, Michael Brainin, Lisa Cronin
    Abstract:

    Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent Stroke in patients with Embolic Stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent Stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent Stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent Stroke in patients with Embolic Stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent Stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction P=0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction P=0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent Stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with Embolic Stroke of undetermined source. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.

  • major bleeding in patients with Embolic Stroke of undetermined source treated with dabigatran versus acetylsalicylic acid re spect esus trial
    Journal of the American College of Cardiology, 2019
    Co-Authors: Christopher B Granger, Hanschristoph Diener, Ralph Sacco, J Easton, Lisa Cronin, Mandy Frasdorf, Claudia Grauer, Martina Brueckmann
    Abstract:

    RE-SPECT ESUS™ offers an opportunity to evaluate factors associated with bleeding risk in patients with Embolic Stroke of unknown source (ESUS) treated with dabigatran vs acetylsalicylic acid (ASA). RE-SPECT ESUS was a randomized, controlled trial (570 centers in 42 countries). Patients with ESUS

  • design of randomized double blind evaluation in secondary Stroke prevention comparing the efficacy and safety of the oral thrombin inhibitor dabigatran etexilate vs acetylsalicylic acid in patients with Embolic Stroke of undetermined source re spect
    International Journal of Stroke, 2015
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Lisa Cronin, Martina Brueckmann, Donald J Easton, Christine Duffy, Daniel Cotton, Ralph L Sacco
    Abstract:

    RationaleCryptogenic ischemic Strokes constitute 20–30% of ischemic Strokes, the majority of which are Embolic Strokes of undetermined source. The standard preventive treatment in these patients is usually acetylsalicylic acid.AimThe Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) is designed to determine whether the oral thrombin inhibitor dabigatran, taken within three-months after Embolic Stroke of undetermined source, is superior to acetylsalicylic acid for prevention of recurrent Stroke and to characterize the safety of dabigatran in this setting.DesignProspective, randomized, double-blind, multicenter trial in approximately 6000 patients and 550 centers with Embolic Stroke of undetermined source. Subjects are randomized to dabigatran or acetylsalicylic acid and treated for an expected minimum of six-m...

  • design of randomized double blind evaluation in secondary Stroke prevention comparing the efficacy and safety of the oral thrombin inhibitor dabigatran etexilate vs acetylsalicylic acid in patients with Embolic Stroke of undetermined source re spect
    International Journal of Stroke, 2015
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Lisa Cronin, Martina Brueckmann, Donald J Easton, Christine Duffy, Daniel Cotton, Ralph L Sacco
    Abstract:

    RationaleCryptogenic ischemic Strokes constitute 20–30% of ischemic Strokes, the majority of which are Embolic Strokes of undetermined source. The standard preventive treatment in these patients is usually acetylsalicylic acid.AimThe Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) is designed to determine whether the oral thrombin inhibitor dabigatran, taken within three-months after Embolic Stroke of undetermined source, is superior to acetylsalicylic acid for prevention of recurrent Stroke and to characterize the safety of dabigatran in this setting.DesignProspective, randomized, double-blind, multicenter trial in approximately 6000 patients and 550 centers with Embolic Stroke of undetermined source. Subjects are randomized to dabigatran or acetylsalicylic acid and treated for an expected minimum of six-m...

Ralph L Sacco - One of the best experts on this subject based on the ideXlab platform.

  • dabigatran or aspirin after Embolic Stroke of undetermined source in patients with patent foramen ovale results from re spect esus
    Stroke, 2021
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Aurauma Chutinet, Donald J Easton, Eva Kleine, Lars Marquardt, Juliane Meyerhoff, Andrea Zini, Ralph L Sacco
    Abstract:

    Background and Purpose: Patent foramen ovale (PFO) may increase the risk of Embolic Stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets...

  • antithrombotic treatment of Embolic Stroke of undetermined source re spect esus elderly and renally impaired subgroups
    Stroke, 2020
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Martina Brueckmann, Richard A Bernstein, Donald J Easton, Ralph L Sacco, Michal Bar, Michael Brainin, Lisa Cronin
    Abstract:

    Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent Stroke in patients with Embolic Stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent Stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent Stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent Stroke in patients with Embolic Stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent Stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction P=0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction P=0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent Stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with Embolic Stroke of undetermined source. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.

  • design of randomized double blind evaluation in secondary Stroke prevention comparing the efficacy and safety of the oral thrombin inhibitor dabigatran etexilate vs acetylsalicylic acid in patients with Embolic Stroke of undetermined source re spect
    International Journal of Stroke, 2015
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Lisa Cronin, Martina Brueckmann, Donald J Easton, Christine Duffy, Daniel Cotton, Ralph L Sacco
    Abstract:

    RationaleCryptogenic ischemic Strokes constitute 20–30% of ischemic Strokes, the majority of which are Embolic Strokes of undetermined source. The standard preventive treatment in these patients is usually acetylsalicylic acid.AimThe Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) is designed to determine whether the oral thrombin inhibitor dabigatran, taken within three-months after Embolic Stroke of undetermined source, is superior to acetylsalicylic acid for prevention of recurrent Stroke and to characterize the safety of dabigatran in this setting.DesignProspective, randomized, double-blind, multicenter trial in approximately 6000 patients and 550 centers with Embolic Stroke of undetermined source. Subjects are randomized to dabigatran or acetylsalicylic acid and treated for an expected minimum of six-m...

  • design of randomized double blind evaluation in secondary Stroke prevention comparing the efficacy and safety of the oral thrombin inhibitor dabigatran etexilate vs acetylsalicylic acid in patients with Embolic Stroke of undetermined source re spect
    International Journal of Stroke, 2015
    Co-Authors: Hanschristoph Diener, Christopher B Granger, Lisa Cronin, Martina Brueckmann, Donald J Easton, Christine Duffy, Daniel Cotton, Ralph L Sacco
    Abstract:

    RationaleCryptogenic ischemic Strokes constitute 20–30% of ischemic Strokes, the majority of which are Embolic Strokes of undetermined source. The standard preventive treatment in these patients is usually acetylsalicylic acid.AimThe Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) is designed to determine whether the oral thrombin inhibitor dabigatran, taken within three-months after Embolic Stroke of undetermined source, is superior to acetylsalicylic acid for prevention of recurrent Stroke and to characterize the safety of dabigatran in this setting.DesignProspective, randomized, double-blind, multicenter trial in approximately 6000 patients and 550 centers with Embolic Stroke of undetermined source. Subjects are randomized to dabigatran or acetylsalicylic acid and treated for an expected minimum of six-m...