Information de reference pour ce titreAccession Number: | 00007670-201209000-00009.
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Author: | Warach, Steven MD, PhD; Al-Rawi, Yasir MBChB; Furlan, Anthony J. MD; Fiebach, Jochen B. MD; Wintermark, Max MD; Lindsten, Annika BSc; Smyej, Jamal BSc; Bharucha, David B. MD; Pedraza, Salvador MD; Rowley, Howard A. MD
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Institution: | From the Seton/University of Texas Southwestern Clinical Research Institute of Austin, TX (S.W.); Signen Biomedical Consulting FZE, United Arab Emirates (Y.A.); Department of Neurology University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (A.J.S.); Center for Stroke Research Berlin, Charite Universitatsmedizin, Berlin, Germany (J.B.F.); Department of Radiology, University of Virginia, Charlottesville, VA (M.W.); H. Lundbeck A/S, Valby, Denmark (A.L., J.S.); Forest Research Institute, Jersey City, NJ (D.B.B.); Department of Radiology IDI-Hospital Dr Josep Trueta de Girona, Girona, Spain (S.P.); Department of Radiology University of Wisconsin, Madison, WI (H.A.R.).
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Title: | |
Source: | Stroke. 43(9):2313-2318, September 2012.
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Abstract: | Background and Purpose-: The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted.
Methods-: In post hoc analyses we assessed the relationships of magnetic resonance imaging-measured lesion volumes with clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch with the clinical effect of desmoteplase in DIAS-2 and in pooled data from DIAS, DEDAS, and DIAS-2.
Results-: In DIAS-2, lesion volumes correlated with National Institutes of Health Stroke Scale (NIHSS) at both baseline and final time points (P<0.0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, desmoteplase was associated with 47% clinical response rate (n=143) vs 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size. The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% confidence interval, 1.16-6.94; P=0.023) for MMV >60 mL. Increasing the minimum NIHSS score for inclusion did not affect treatment effect size.
Conclusions-: Pooled across all desmoteplase trials, desmoteplase appears beneficial in patients with large MMV and ineffective in patients with small MMV. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later time-window thrombolytic trials.
Clinical Trial Registration-: URL: http://www.clinicaltrials.gov- ouverture dans une nouvelle fenêtre. Unique Identifiers: NCT00638781, NCT00638248, NCT00111852.
(C) 2012 American Heart Association, Inc.
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Author Keywords: | acute cerebral infarction; desmoteplase; diffusion-weighted imaging; magnetic resonance imaging; mismatch; perfusion; stroke; thrombolysis.
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References: | 1. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333:1581-1587.
2. Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, et al.. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 2010;375:1695-1703.
3. Donnan GA, Baron JC, Ma H, Davis SM. Penumbral selection of patients for trials of acute stroke therapy. Lancet Neurol. 2009;8:261-269.
4. Warach S. Thrombolysis in stroke beyond three hours: Targeting patients with diffusion and perfusion MRI. Ann Neurol. 2002;51:11-13.
5. Albers GW. Expanding the window for thrombolytic therapy in acute stroke. The potential role of acute MRI for patient selection. Stroke. 1999;30:2230-2237.
6. Baird AE, Benfield A, Schlaug G, Siewert B, Lovblad KO, Edelman RR, et al.. Enlargement of human cerebral ischemic lesion volumes measured by diffusion-weighted magnetic resonance imaging. Ann Neurol. 1997;41:581-589.
7. Warach S, Pettigrew LC, Dashe JF, Pullicino P, Lefkowitz DM, Sabounjian L, et al.. Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging. Citicoline 010 Investigators. Ann Neurol. 2000;48:713-722.
8. Beaulieu C, de Crespigny A, Tong DC, Moseley ME, Albers GW, Marks MP. Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke: evolution of lesion volume and correlation with clinical outcome. Ann Neurol. 1999;46:568-578.
9. Lovblad KO, Baird AE, Schlaug G, Benfield A, Siewert B, Voetsch B, et al.. Ischemic lesion volumes in acute stroke by diffusion-weighted magnetic resonance imaging correlate with clinical outcome. Ann Neurol. 1997;42:164-170.
10. Chalela JA, Kang DW, Luby M, Ezzeddine M, Latour LL, Todd JW, et al.. Early magnetic resonance imaging findings in patients receiving tissue plasminogen activator predict outcome: Insights into the pathophysiology of acute stroke in the thrombolysis era. Ann Neurol. 2004;55:105-112.
11. Merino JG, Latour LL, Todd JW, Luby M, Schellinger PD, Kang DW, et al.. Lesion volume change after treatment with tissue plasminogen activator can discriminate clinical responders from nonresponders. Stroke. 2007;38:2919-2923.
12. Hacke W, Albers G, Al-Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, et al.. The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke. 2005;36:66-73.
13. Furlan AJ, Eyding D, Albers GW, Al-Rawi Y, Lees KR, Rowley HA, et al.. Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset. Stroke. 2006;37:1227-1231.
14. Hacke W, Furlan AJ, Al-Rawi Y, Davalos A, Fiebach JB, Gruber F, et al.. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2009;8:141-150.
15. Albers GW, Thijs VN, Wechsler L, Kemp S, Schlaug G, Skalabrin E, et al.. Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Ann Neurol. 2006;60:508-517.
16. Davis SM, Donnan GA, Parsons MW, Levi C, Butcher KS, Peeters A, et al.. Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial. Lancet Neurol. 2008;7:299-309.
17. Olivot JM, Mlynash M, Thijs VN, Kemp S, Lansberg MG, Wechsler L, et al.. Optimal Tmax threshold for predicting penumbral tissue in acute stroke. Stroke. 2009;40:469-475.
18. Takasawa M, Jones PS, Guadagno JV, Christensen S, Fryer TD, Harding S, et al.. How reliable is perfusion MR in acute stroke? Validation and determination of the penumbra threshold against quantitative PET. Stroke. 2008;39:870-877.
19. Rohl L, Ostergaard L, Simonsen CZ, Vestergaard-Poulsen P, Andersen G, et al.. Viability thresholds of ischemic penumbra of hyperacute stroke defined by perfusion-weighted MRI and apparent diffusion coefficient. Stroke. 2001;32:1140-1146.
20. Kane I, Carpenter T, Chappell F, Rivers C, Armitage P, Sandercock P, et al.. Comparison of 10 different magnetic resonance perfusion imaging processing methods in acute ischemic stroke: effect on lesion size, proportion of patients with diffusion/perfusion mismatch, clinical scores, and radiologic outcomes. Stroke. 2007;38:3158-3164.
21. Kakuda W, Lansberg MG, Thijs VN, Kemp SM, Bammer R, Wechsler LR, et al.. Optimal definition for PWI/DWI mismatch in acute ischemic stroke patients. J Cereb Blood Flow Metab. 2008;28:887-891.
22. Luby M, Bykowski JL, Schellinger PD, Merino JG, Warach S. Intra- and interrater reliability of ischemic lesion volume measurements on diffusion-weighted, mean transit time and fluid-attenuated inversion recovery MRI. Stroke. 2006;37:2951-2956.
23. Luby M, Ku KD, Latour LL, Merino JG, Hsia AW, Lynch JK, Warach S. Visual perfusion-diffusion mismatch is equivalent to quantitative mismatch. Stroke. 2011;42:1010-1014.
24. Christensen S, Mouridsen K, Wu O, Hjort N, Karstoft H, Thomalla G, et al.. Comparison of 10 perfusion MRI parameters in 97 sub-6-hour stroke patients using voxel-based receiver operating characteristics analysis. Stroke. 2009;40:2055-2061.
25. Schellinger PD, Latour LL, Wu CS, Chalela JA, Warach S. The association between neurological deficit in acute ischemic stroke and mean transit time: comparison of four different perfusion MRI algorithms. Neuroradiology. 2006;48:69-77.
26. Grandin CB, Duprez TP, Smith AM, Oppenheim C, Peeters A, Robert AR, et al.. Which MR-derived perfusion parameters are the best predictors of infarct growth in hyperacute stroke? Comparative study between relative and quantitative measurements. Radiology. 2002;223:361-370.
27. Kudo K, Sasaki M, Ostergaard L, Christensen S, Uwano I, Suzuki M, et al.. Susceptibility of Tmax to tracer delay on perfusion analysis: quantitative evaluation of various deconvolution algorithms using digital phantoms. J Cereb Blood Flow Metab. 2011;31:908-912.
28. Lansberg MG, Lee J, Christensen S, Straka M, De Silva DA, Mlynash M, et al.. RAPID automated patient selection for reperfusion therapy: a pooled analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study. Stroke. 2011;42:1608-1614.
29. Wintermark M, Albers GW, Alexandrov AV, Alger JR, Bammer R, Baron JC, et al.. Acute stroke imaging research roadmap. Stroke. 2008;39:1621-1628.
30. Fiebach JB, Al-Rawi Y, Wintermark M, Furlan AJ, Rowley HA, Lindsten A, et al.. Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase. Stroke. 2012;43:1561-1566.
31. Parsons MW, Christensen S, McElduff P, Levi CR, Butcher KS, De Silva DA, et al.. Pretreatment diffusion- and perfusion-MR lesion volumes have a crucial influence on clinical response to stroke thrombolysis. J Cereb Blood Flow Metab. 2010;30:1214-1225.
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Language: | English.
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Document Type: | Original Contributions; Clinical Sciences.
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Journal Subset: | Clinical Medicine.
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ISSN: | 0039-2499
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NLM Journal Code: | v2j, 0235266
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DOI Number: | https://dx.doi.org/10.1161/STROK...- ouverture dans une nouvelle fenêtre
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