Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke
Open accessAbstract
BACKGROUND: Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke. METHODS: After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. RESULTS: We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alteplase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P=0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0% vs. 17.6%; P=0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%; P=0.008). Mortality did not differ significantly between the alteplase and placebo groups (7.7% and 8.4%, respectively; P=0.68). There was no significant difference in the rate of other serious adverse events. CONCLUSIONS: As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage. (ClinicalTrials.gov number, NCT00153036.)
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
If the risk of hazard (hemorrhage) is relatively low, then a shift analysis may still be efficient, as reported in ECASS-3.
“In this example, if the risk of hazard (hemorrhage) is relatively low, then a shift analysis may still be efficient, as reported in ECASS-3 (Figure 1). 39”
From Statistical Analysis of the Primary Outcome in Acute Stroke Trials (2012) · cites this paper as [39]
The Efficacy section reports that a post hoc analysis across modified Rankin scale scores favored alteplase (P=0.02), and the safety results report symptomatic intracranial hemorrhage in 2.4% of alteplase recipients. The paper does not test whether a low hemorrhage risk makes shift analysis statistically efficient, so that conditional methodological conclusion is not supported. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Functional evaluation : Barthel index
Mahonery, F. I. (1965) · Medical Entomology and Zoology · Cited by 12,762 · see citing works
Tissue Plasminogen Activator for Acute Ischemic Stroke
(1995) · New England Journal of Medicine · doi:10.1056/nejm199512143332401 · Cited by 11,654 · see citing works
ASSESSMENT OF OUTCOME AFTER SEVERE BRAIN DAMAGE A Practical Scale
JENNETT, B. (1975) · The Lancet · doi:10.1016/s0140-6736(75)92830-5 · Cited by 7,501 · see citing works
Interobserver agreement for the assessment of handicap in stroke patients
van Swieten, J. C., Koudstaal, P. J., Visser, M. C., Schouten, H. J., & van Gijn, J. (1988) · Stroke · doi:10.1161/01.str.19.5.604 · Cited by 6,512 · see citing works
Measurements of acute cerebral infarction: a clinical examination scale.
Brott, T. G., Adams, H. P., Olinger, C. P., Marler, J. R., Barsan, W. G., Biller, J., Spilker, J. A., Holleran, R. S., EBERLE, R. W., & Hertzberg, V. (1989) · Stroke · doi:10.1161/01.str.20.7.864 · Cited by 5,918 · see citing works
Hacke, W., Kaste, M., Fieschi, C., von Kummer, R., Davalos, A., Meier, D., Larrue, V., Bluhmki, E., Davis, S., Donnan, G., et al. (1998) · The Lancet · doi:10.1016/s0140-6736(98)08020-9 · Cited by 3,662 · see citing works
Self-citationIntravenous Thrombolysis With Recombinant Tissue Plasminogen Activator for Acute Hemispheric Stroke
Hacke, W. (1995) · JAMA · doi:10.1001/jama.274.13.1017 · Cited by 3,661 · see citing works
Self-citationHacke, W., Donnan, G. A., Fieschi, C., Kaste, M., von Kummer, R., Broderick, J. P., Brott, T. G., Frankel, M., Grotta, J. C., Haley, E. C., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)15692-4 · Cited by 2,561 · see citing works
Self-citationGuidelines for Management of Ischaemic Stroke and Transient Ischaemic Attack 2008
The European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee (2008) · Cerebrovascular Diseases · doi:10.1159/000131083 · Cited by 2,475 · see citing works
Guidelines for the Early Management of Adults With Ischemic Stroke
Adams, H. P., del Zoppo, G., Alberts, M. J., Bhatt, D. L., Brass, L. M., Furlan, A. J., Grubb, R. L., Higashida, R. T., Jauch, E. C., Kidwell, C. S., et al. (2007) · Stroke · doi:10.1161/strokeaha.107.181486 · Cited by 2,461 · see citing works
Wahlgren, N. G., Ahmed, N., Dávalos, A., Ford, G. A., Grond, M., Hacke, W., Hennerici, M. G., Kaste, M., Külkens, S., Larrue, V., et al. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60149-4 · Cited by 2,375 · see citing works
Self-citationClark, W. M., Wissman, S., Albers, G. W., Jhamandas, J. H., Madden, K. P., Hamilton, S., & for the ATLANTIS Study Investigators (1999) · JAMA · doi:10.1001/jama.282.21.2019 · Cited by 1,180 · see citing works
Clinical interpretation and use of stroke scales
Kasner, S. E. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70495-1 · Cited by 947 · see citing works
Intracerebral Hemorrhage After Intravenous t-PA Therapy for Ischemic Stroke
The NINDS t-PA Stroke Study Group (1997) · Stroke · doi:10.1161/01.str.28.11.2109 · Cited by 879 · see citing works
Early stroke treatment associated with better outcome
Marler, J. R., Tilley, B. C., Lü, M., Brott, T. G., Lyden, P., Grotta, J. C., Broderick, J. P., Levine, S. R., Frankel, M., Horowitz, S. H., et al. (2000) · Neurology · doi:10.1212/wnl.55.11.1649 · Cited by 856 · see citing works
NXY-059 for Acute Ischemic Stroke
Lees, K. R., Zivin, J. A., Ashwood, T., Davalos, A., Davis, S. M., Diener, H.-C., Grotta, J., Lyden, P., Shuaib, A., Hårdemark, H.-G., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052980 · Cited by 660 · see citing works
Self-citationThe rtPA (Alteplase) 0- to 6-Hour Acute Stroke Trial, Part A (A0276g)
Clark, W. M., Albers, G. W., Madden, K. P., & Hamilton, S. (2000) · Stroke · doi:10.1161/01.str.31.4.811 · Cited by 416 · see citing works
Lansberg, M. G., Albers, G. W., & Wijman, C. A. C. (2007) · Cerebrovascular Diseases · doi:10.1159/000103110 · Cited by 239 · see citing works
Tilley, B. C., Marler, J. R., Geller, N. L., Lü, M., Legler, J. M., Brott, T. G., Lyden, P. D., & Grotta, J. C. (1996) · Stroke · doi:10.1161/01.str.27.11.2136 · Cited by 227 · see citing works
Quinn, T. J., Lees, K. R., Hårdemark, H., Dawson, J., & Walters, M. R. (2007) · Stroke · doi:10.1161/strokeaha.106.480723 · Cited by 126 · see citing works
Self-citationSavitz, S. I., Lew, R., Bluhmki, E., Hacke, W., & Fisher, M. (2007) · Stroke · doi:10.1161/strokeaha.107.489351 · Cited by 119 · see citing works
Self-citationGlobal tests for multiple binary outcomes
Lefkopoulou, M., & Ryan, L. (1993) · Biometrics · doi:10.2307/2532240 · Cited by 114 · see citing works
Intravenous alteplase for ischaemic stroke
Albers, G. W., & Olivot, J. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60120-2 · Cited by 80 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [11]11. Albers GW, Olivot JM. Intravenous alte- plase for ischaemic stroke. Lancet 2007; 369:249-50.
Cited by
Sorted by citations
Guidelines for the Early Management of Patients With Acute Ischemic Stroke
Jauch, E. C., Saver, J. L., Adams, H. P., Bruno, A., Connors, J. J. “., Demaerschalk, B. M., Khatri, P., McMullan, P. W., Qureshi, A. I., Rosenfield, K., et al. (2013) · Stroke · doi:10.1161/str.0b013e318284056a · Cited by 7,648 · see citing works
Powers, W. J., Rabinstein, A. A., Ackerson, T., Adeoye, O. M., Bambakidis, N. C., Becker, K. J., Biller, J., Brown, M., Demaerschalk, B. M., Hoh, B. L., et al. (2019) · Stroke · doi:10.1161/str.0000000000000211 · Cited by 7,673 · see citing works
Whelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Dennison Himmelfarb, C., DePalma, S. M., Gidding, S., Jamerson, K. A., Jones, D. W., et al. (2018) · Hypertension · doi:10.1161/hyp.0000000000000065 · Cited by 7,391 · see citing works
A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke
Berkhemer, O. A., Fransen, P. S. S., Beumer, D., van den Berg, L. A., Lingsma, H. F., Yoo, A. J., Schonewille, W. J., Vos, J. A., Nederkoorn, P. J., Wermer, M. J. H., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1411587 · Cited by 6,674 · see citing works
Whelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Dennison Himmelfarb, C., DePalma, S. M., Gidding, S., Jamerson, K. A., Jones, D. W., et al. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.11.006 · Cited by 6,616 · see citing works
Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct
Nogueira, R. G., Jadhav, A. P., Haussen, D. C., Bonafé, A., Budzik, R. F., Bhuva, P., Yavagal, D. R., Ribó, M., Cognard, C., Hanel, R. A., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1706442 · Cited by 5,667 · see citing works
Powers, W. J., Rabinstein, A. A., Ackerson, T., Adeoye, O. M., Bambakidis, N. C., Becker, K. J., Biller, J., Brown, M., Demaerschalk, B. M., Hoh, B. L., et al. (2018) · Stroke · doi:10.1161/str.0000000000000158 · Cited by 5,505 · see citing works
Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke
Saver, J. L., Goyal, M., Bonafé, A., Diener, H., Levy, E. I., Pereira, V. M., Albers, G. W., Cognard, C., Cohen, D. J., Hacke, W., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1415061 · Cited by 5,201 · see citing works
Self-citationWhelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Dennison Himmelfarb, C., DePalma, S. M., Gidding, S., Jamerson, K. A., Jones, D. W., et al. (2018) · Hypertension · doi:10.1161/hyp.0000000000000066 · Cited by 4,347 · see citing works
Pantoni, L. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70104-6 · Cited by 3,405 · see citing works
Emberson, J., Lees, K. R., Lyden, P., Blackwell, L., Albers, G., Bluhmki, E., Brott, T., Cohen, G., Davis, S., Donnan, G., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60584-5 · Cited by 2,737 · see citing works
Self-citationLees, K., Bluhmki, E., von Kummer, R., Brott, T., Toni, D., Grotta, J., Albers, G., Kaste, M., Marler, J., Hamilton, S., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60491-6 · Cited by 2,182 · see citing works
Self-citationPart 14: Pediatric Advanced Life Support
Kleinman, M. E., Chameides, L., Schexnayder, S. M., Samson, R. A., Hazinski, M. F., Atkins, D. L., Berg, M., de Caen, A. R., Fink, E. L., Freid, E. B., et al. (2010) · Circulation · doi:10.1161/circulationaha.110.971101 · Cited by 1,951 · see citing works
Aoki, J., Kimura, K., Shibazaki, K., & Sakamoto, Y. (2013) · Cerebrovascular Diseases Extra · doi:10.1159/000348552 · Cited by 1,929 · see citing works
Thrombolysis for acute ischaemic stroke
Wardlaw, J. M., Murray, V., Berge, E., & del Zoppo, G. J. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd000213.pub3 · Cited by 1,460 · see citing works
The Heidelberg Bleeding Classification
von Kummer, R., Broderick, J. P., Campbell, B. C. V., Demchuk, A. M., Goyal, M., Hill, M. D., Treurniet, K. M., Majoie, C. B. L. M., Marquering, H. A., Mazya, M. V., et al. (2015) · Stroke · doi:10.1161/strokeaha.115.010049 · Cited by 1,430 · see citing works
Self-citationA Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke
Kidwell, C. S., Jahan, R., GORNBEIN, J. A., Alger, J. R., Nenov, V., Ajani, Z. A., Feng, L., Meyer, B. C., Olson, S. E., Schwamm, L. H., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1212793 · Cited by 1,381 · see citing works
European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke
Berge, E., Whiteley, W. N., Audebert, H. J., Marchis, G. D., Fonseca, A. C., Padiglioni, C., de la Ossa, N. P., Strbian, D., Tsivgoulis, G. K., & Turc, G. (2021) · European Stroke Journal · doi:10.1177/2396987321989865 · Cited by 1,392 · see citing works
Global Epidemiology of Stroke and Access to Acute Ischemic Stroke Interventions
Saini, V. A., Guada, L. G., & Yavagal, D. R. (2021) · Neurology · doi:10.1212/wnl.0000000000012781 · Cited by 1,366 · see citing works
MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset
Thomalla, G., Simonsen, C. Z., Boutitie, F., Andersen, G., Berthezène, Y., Cheng, B., Cheripelli, B. K., Cho, T., Fazekas, F., Fiehler, J., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1804355 · Cited by 1,346 · see citing works
Bracard, S., Ducrocq, X., Mas, J., Soudant, M., Oppenheim, C., Moulin, T., & Guillemin, F. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30177-6 · Cited by 1,203 · see citing works
‡ (2012) · The Lancet · doi:10.1016/s0140-6736(12)60768-5 · Cited by 1,188 · see citing works
Nogueira, R. G., Lutsep, H. L., Gupta, R. G., Jovin, T. G., Albers, G. W., Walker, G. A., Liebeskind, D. S., & Smith, W. S. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61299-9 · Cited by 1,109 · see citing works
Whelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Dennison Himmelfarb, C., DePalma, S. M., Gidding, S., Jamerson, K. A., Jones, D. W., et al. (2018) · Circulation · doi:10.1161/cir.0000000000000596 · Cited by 1,127 · see citing works
Wardlaw, J. M., Murray, V., Berge, E., del Zoppo, G., Sandercock, P. A., Lindley, R. I., & Cohen, G. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60738-7 · Cited by 1,007 · see citing works
Whelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Himmelfarb, C. D., DePalma, S. M., Gidding, S. S., Jamerson, K., Jones, D. W., et al. (2018) · Circulation · doi:10.1161/cir.0000000000000597 · Cited by 989 · see citing works
Whelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Himmelfarb, C. D., DePalma, S. M., Gidding, S. S., Jamerson, K., Jones, D. W., et al. (2018) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2018.06.010 · Cited by 947 · see citing works
Management of Acute Ischemic Stroke
Herpich, F., & Rincón, F. (2020) · Critical Care Medicine · doi:10.1097/ccm.0000000000004597 · Cited by 945 · see citing works
Whelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Himmelfarb, C. D., DePalma, S. M., Gidding, S. S., Jamerson, K., Jones, D. W., et al. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.11.005 · Cited by 934 · see citing works
Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke
Yang, C., Hawkins, K. E., Doré, S., & Candelario-Jalil, E. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00136.2018 · Cited by 871 · see citing works
Feske, S. K. (2021) · The American Journal of Medicine · doi:10.1016/j.amjmed.2021.07.027 · Cited by 835 · see citing works
del Zoppo, G. J., Saver, J. L., Jauch, E. C., & Adams, H. P. (2009) · Stroke · doi:10.1161/strokeaha.109.192535 · Cited by 827 · see citing works
Lackland, D. T., Roccella, E. J., Deutsch, A. F., Fornage, M., George, M. G., Howard, G., Kissela, B. M., Kittner, S. J., Lichtman, J. H., Lisabeth, L. D., et al. (2014) · Stroke · doi:10.1161/01.str.0000437068.30550.cf · Cited by 815 · see citing works
Evolution of the Modified Rankin Scale and Its Use in Future Stroke Trials
Broderick, J. P., Adeoye, O. M., & Elm, J. (2017) · Stroke · doi:10.1161/strokeaha.117.017866 · Cited by 813 · see citing works
Extracranial-Intracranial Bypass Surgery for Stroke Prevention in Hemodynamic Cerebral Ischemia
Powers, W. J., Clarke, W. R., Grubb, R. L., Videen, T. O., Adams, H. P., Derdeyn, C. P., & for the COSS Investigators (2011) · JAMA · doi:10.1001/jama.2011.1610 · Cited by 818 · see citing works
Schonewille, W. J., Wijman, C. A. C., Michel, P., Rueckert, C. M., Weimar, C., Mattle, H. P., Engelter, S. T., Tanné, D., Muir, K. W., Molina, C. A., et al. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70173-5 · Cited by 778 · see citing works
Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications
Tuo, Q., Zhang, S., & Lei, P. (2021) · Medicinal Research Reviews · doi:10.1002/med.21817 · Cited by 747 · see citing works
“However, the proteolytic activities of r‐tPA can induce side effects such as blood‐brain barrier breakdown and intracranial hemorrhage,(338) and reduce the therapeutic time window.(339) I/R injury is also a common occurrence after blood flow is restored,340‐342 which is why the identification of novel neuroprotectants…”
BackgroundBhatia, R., Hill, M. D., Shobha, N., Menon, B. K., Bal, S. S., Kochar, P. S., Watson, T., Goyal, M., & Demchuk, A. M. (2010) · Stroke · doi:10.1161/strokeaha.110.592535 · Cited by 726 · see citing works
Part 5: Adult Basic Life Support
Berg, R. A., Hemphill, R., Abella, B. S., Aufderheide, T. P., Cave, D. M., Hazinski, M. F., Lerner, E. B., Rea, T. D., Sayre, M. R., & Swor, R. A. (2010) · Circulation · doi:10.1161/circulationaha.110.970939 · Cited by 719 · see citing works
Hilkens, N. A., Casolla, B., Leung, T. W. H., & de Leeuw, F. (2024) · The Lancet · doi:10.1016/s0140-6736(24)00642-1 · Cited by 724 · see citing works
Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage
Frontera, J. A., Lewin, J. J., Rabinstein, A. A., Aisiku, I. P., Alexandrov, A. W., Cook, A. M., del Zoppo, G. J., Kumar, M. A., Peerschke, E. I. B., Stiefel, M., et al. (2015) · Neurocritical Care · doi:10.1007/s12028-015-0222-x · Cited by 713 · see citing works
Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke
Xiong, X., Liu, L., & Yang, Q. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.05.001 · Cited by 703 · see citing works
Overcoming the Blood–Brain Barrier: The Role of Nanomaterials in Treating Neurological Diseases
Furtado, D., Björnmalm, M., Ayton, S., Bush, A. I., Kempe, K., & Caruso, F. (2018) · Advanced Materials · doi:10.1002/adma.201801362 · Cited by 708 · see citing works
A Randomized Trial of Tenecteplase versus Alteplase for Acute Ischemic Stroke
Parsons, M. W., Spratt, N. J., Bivard, A., Campbell, B. C. V., Chung, K., Miteff, F., O’Brien, B., Bladin, C., McElduff, P., Allen, C., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1109842 · Cited by 679 · see citing works
Prabhakaran, S., Ruff, I., & Bernstein, R. A. (2015) · JAMA · doi:10.1001/jama.2015.3058 · Cited by 675 · see citing works
Demaerschalk, B. M., Kleindorfer, D. O., Adeoye, O. M., Demchuk, A. M., Fugate, J. E., Grotta, J. C., Khalessi, A. A., Levy, E. I., Palesch, Y. Y., Prabhakaran, S., et al. (2016) · Stroke · doi:10.1161/str.0000000000000086 · Cited by 670 · see citing works
Management of acute ischemic stroke
Phipps, M., & Cronin, C. A. (2020) · BMJ · doi:10.1136/bmj.l6983 · Cited by 654 · see citing works
Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities.
Rodrigo, R., Fernández-Gajardo, R., Gutiérrez, R., Matamala, J. M., Carrasco, R., Miranda-Merchak, A., & Feuerhake, W. (2013) · CNS and Neurological Disorders - Drug Targets · doi:10.2174/1871527311312050015 · Cited by 621 · see citing works
Recombinant Human Erythropoietin in the Treatment of Acute Ischemic Stroke
Ehrenreich, H., Weissenborn, K., Prange, H., Schneider, D., Weimar, C., Wartenberg, K., Schellinger, P. D., Bohn, M., Becker, H., Wegrzyn, M., et al. (2009) · Stroke · doi:10.1161/strokeaha.109.564872 · Cited by 605 · see citing works
Self-citationThomalla, G., Cheng, B., Ebinger, M., Hao, Q., Tourdias, T., Wu, O., Kim, J. S., Breuer, L., Singer, O. C., Warach, S. J., et al. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70192-2 · Cited by 604 · see citing works
Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic
Zhang, Z. G., & Chopp, M. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70061-4 · Cited by 596 · see citing works
Hacke, W., Furlan, A. J., Al‐Rawi, Y., Dávalos, A., Fiebach, J. B., Gruber, F., Kaste, M., Lipka, L., Pedraza, S., Ringleb, P. A., et al. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70267-9 · Cited by 568 · see citing works
Self-citationReducing in-hospital delay to 20 minutes in stroke thrombolysis
Meretoja, A., Strbian, D., Mustanoja, S. M., Tatlisumak, T., Lindsberg, P. J., & Kaste, M. (2012) · Neurology · doi:10.1212/wnl.0b013e31825d6011 · Cited by 561 · see citing works
Self-citationHemorrhagic Transformation after Ischemic Stroke in Animals and Humans
Jickling, G. C., Liu, D., Stamova, B. S., Ander, B. P., Zhan, X., Lu, A., & Sharp, F. R. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.203 · Cited by 550 · see citing works
Fransen, P. S. S., Beumer, D., Berkhemer, O. A., van den Berg, L. A., Lingsma, H. F., van der Lugt, A., van Zwam, W. H., van Oostenbrugge, R. J., Roos, Y. B. W. E. M., Majoie, C. B. L. M., et al. (2014) · Trials · doi:10.1186/1745-6215-15-343 · Cited by 550 · see citing works
Yaghi, S. R., Willey, J. Z., Cucchiara, B. L., Goldstein, J. N., Gonzales, N. R., Khatri, P., Kim, L. J., Mayer, S. A., Sheth, K. N., & Schwamm, L. H. (2017) · Stroke · doi:10.1161/str.0000000000000152 · Cited by 555 · see citing works
Thrombus Composition and Efficacy of Thrombolysis and Thrombectomy in Acute Ischemic Stroke
Jolugbo, P., & Ariëns, R. A. S. (2021) · Stroke · doi:10.1161/strokeaha.120.032810 · Cited by 533 · see citing works
“5 hours of symptom onset.(59,75) Successful treatment of AIS with tPA is particularly time-dependent with efficacy quickly declining with time.”
BackgroundJurcău, A., & Simion, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010014 · Cited by 515 · see citing works
Good clinical outcome after ischemic stroke with successful revascularization is time-dependent
Khatri, P., Abruzzo, T. A., Yeatts, S. D., Nichols, C., Broderick, J. P., & Tomsick, T. A. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b9c847 · Cited by 491 · see citing works
Walter, S., Kostopoulos, P., Haass, A., Keller, I., Lesmeister, M., Schlechtriemen, T., Roth, C., Papanagiotou, P., Grunwald, I. Q., Schumacher, H., et al. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70057-1 · Cited by 486 · see citing works
Menon, B. K., Buck, B. H., Singh, N., Deschaintre, Y., Almekhlafi, M., Coutts, S. B., Thirunavukkarasu, S., Khosravani, H., Appireddy, R., Moreau, F., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(22)01054-6 · Cited by 490 · see citing works
Logallo, N., Novotný, V., Aßmus, J., Kvistad, C. E., Alteheld, L., Rønning, O. M., Thommessen, B., Amthor, K.-F., Ihle‐Hansen, H., Kurz, M. W., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30253-3 · Cited by 464 · see citing works
Leucht, S., Hierl, S., Kissling, W., Dold, M., & Davis, J. M. (2012) · British Journal of Psychiatry · doi:10.1192/bjp.bp.111.096594 · Cited by 451 · see citing works
Antithrombotic and Thrombolytic Therapy for Ischemic Stroke
Lansberg, M. G., O'Donnell, M. J., Khatri, P., Lang, E., Nguyen‐Huynh, M. N., Schwartz, N. E., Sonnenberg, F. A., Schulman, S., Vandvik, P. O., Spencer, F. A., et al. (2012) · CHEST Journal · doi:10.1378/chest.11-2302 · Cited by 454 · see citing works
Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain
Cook, D. J., Teves, L. M., & Tymianski, M. (2012) · Nature · doi:10.1038/nature10841 · Cited by 446 · see citing works
Effect of the Use of Ambulance-Based Thrombolysis on Time to Thrombolysis in Acute Ischemic Stroke
Ebinger, M., Winter, B., Wendt, M., Weber, J. E., Waldschmidt, C., Różański, M., Kunz, A. B., Koch, P. M., Kellner, P. A., Gierhake, D., et al. (2014) · JAMA · doi:10.1001/jama.2014.2850 · Cited by 444 · see citing works
Middleton, S., McElduff, P., Ward, J., Grimshaw, J., Dale, S., D’Este, C. A., Drury, P., Griffiths, R., Cheung, N. W., Quinn, C., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)61485-2 · Cited by 420 · see citing works
Texture Analysis: A Review of Neurologic MR Imaging Applications
Kassner, A., & Thornhill, R. E. (2010) · American Journal of Neuroradiology · doi:10.3174/ajnr.a2061 · Cited by 407 · see citing works
Gong, P., Liu, Y., Gong, Y., Chen, G., Zhang, X., Wang, S., Zhou, F., Duan, R., Chen, W., Huang, T., et al. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02090-6 · Cited by 399 · see citing works
Novel Stroke Therapeutics: Unraveling Stroke Pathophysiology and Its Impact on Clinical Treatments
George, P. M., & Steinberg, G. K. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.041 · Cited by 394 · see citing works
Liu, J., Jin, X., Liu, K. J., & Liu, W. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.6409-11.2012 · Cited by 434 · see citing works
Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke
Lakhan, S., Kirchgessner, A., Tepper, D. E., & Leonard, A. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00032 · Cited by 379 · see citing works
Mazya, M. V., Egido, J. A., Ford, G. A., Lees, K. R., Mikulík, R., Toni, D., Wahlgren, N. G., & Ahmed, N. (2012) · Stroke · doi:10.1161/strokeaha.111.644815 · Cited by 384 · see citing works
Self-citationThrombolysis for acute ischaemic stroke: current status and future perspectives
Tsivgoulis, G. K., Katsanos, A. H., Sandset, E. C., Turc, G., Nguyen, T. N., Bivard, A., Fischer, U., & Khatri, P. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00519-1 · Cited by 382 · see citing works
Recent advances in the management of acute ischemic stroke
Chang, P., & Prabhakaran, S. (2017) · F1000Research · doi:10.12688/f1000research.9191.1 · Cited by 379 · see citing works
Hess, D. C., Wechsler, L. R., Clark, W. M., Savitz, S. I., Ford, G. A., Chiu, D. T. W., Yavagal, D. R., Uchino, K., Liebeskind, D. S., Auchus, A. P., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30046-7 · Cited by 370 · see citing works
Diagnosis and management of acute ischemic stroke: speed is critical
Musuka, T. D., Wilton, S. B., Traboulsi, M., & Hill, M. D. (2015) · Canadian Medical Association Journal · doi:10.1503/cmaj.140355 · Cited by 369 · see citing works
Ahmed, N., Wahlgren, N. G., Brainin, M., Castillo, J., Ford, G. A., Kaste, M., Lees, K. R., & Toni, D. (2009) · Stroke · doi:10.1161/strokeaha.109.548602 · Cited by 359 · see citing works
Self-citationBertog, S. C., Sievert, K., Grunwald, I. Q., Sharma, A. N., Hornung, M., Kühn, A. L., Vaškelytė, L., Hofmann, I., Gafoor, S. A., Reinartz, M., et al. (2022) · Interventional Cardiology · doi:10.1002/9781119697367.ch71 · Cited by 356 · see citing works
Bacigaluppi, M., Pluchino, S., Jametti, L. P., Kilic, E., Kilic, Ü., Salani, G., Brambilla, E., West, M. J., Comi, G., Martino, G., et al. (2009) · Brain · doi:10.1093/brain/awp174 · Cited by 350 · see citing works
Liu, L., Chen, W., Zhou, H., Duan, W., Li, S., Huo, X., Xu, W., Huang, L., Zheng, H., Liu, J., et al. (2020) · Stroke and Vascular Neurology · doi:10.1136/svn-2020-000378 · Cited by 350 · see citing works
Han, L., & Jiang, C. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.11.023 · Cited by 358 · see citing works
Bluhmki, E., Chamorro, Á., Dávalos, A., Machnig, T., Sauce, C., Wahlgren, N. G., Wardlaw, J. M., & Hacke, W. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70264-9 · Cited by 345 · see citing works
Self-citationIntravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L)
Hemmen, T., Raman, R., Guluma, K. Z., Meyer, B. C., Gomes, J. A., Cruz‐Flores, S., Wijman, C. A. C., Rapp, K. S., Grotta, J. C., & Lyden, P. D. (2010) · Stroke · doi:10.1161/strokeaha.110.592295 · Cited by 343 · see citing works
Acute ischemic stroke therapy overview
Catanese, L., Tarsia, J., & Fisher, M. (2017) · Circulation Research · doi:10.1161/circresaha.116.309278 · Cited by 341 · see citing works
Pathogenesis of acute stroke and the role of inflammasomes
Fann, D. Y., Lee, S.-Y., Manzanero, S., Chunduri, P., Sobey, C. G., & Arumugam, T. V. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.09.004 · Cited by 334 · see citing works
Huang, X., Cheripelli, B. K., Lloyd, S. M., Kalladka, D., Moreton, F. C., Siddiqui, A., Ford, I., & Muir, K. W. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70017-7 · Cited by 332 · see citing works
Schellinger, P. D., Bryan, R. N., Caplan, L. R., Detre, J. A., Edelman, R. R., Jaigobin, C. S., Kidwell, C. S., Mohr, J. P., Sloan, M. A., Sorensen, A. G., et al. (2010) · Neurology · doi:10.1212/wnl.0b013e3181e7c9dd · Cited by 333 · see citing works
Jones, D. W., Ferdinand, K. C., Taler, S. J., Johnson, H. M., Shimbo, D., Abdalla, M., Altieri, M. M., Bansal, N., Bello, N. A., Bress, A. P., et al. (2025) · Hypertension · doi:10.1161/hyp.0000000000000249 · Cited by 386 · see citing works
Wang, Y., Li, S., Pan, Y., Li, H., Parsons, M. W., Campbell, B. C. V., Schwamm, L. H., Fisher, M., Che, F., Dai, H., et al. (2023) · The Lancet · doi:10.1016/s0140-6736(22)02600-9 · Cited by 326 · see citing works
Stroke Prognostication using Age and NIH Stroke Scale
Saposnik, G., Guzik, A. K., Reeves, M. J., Ovbiagele, B. I., & Johnston, S. C. (2012) · Neurology · doi:10.1212/wnl.0b013e31827b1ace · Cited by 318 · see citing works
Streamlining of prehospital stroke management: the golden hour
Fassbender, K. C., Balucani, C., Walter, S., Levine, S. R., Haass, A., & Grotta, J. C. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70100-5 · Cited by 318 · see citing works
Ischemia-Reperfusion Injury in Stroke
Nour, M., Scalzo, F., & Liebeskind, D. S. (2012) · Interventional Neurology · doi:10.1159/000353125 · Cited by 316 · see citing works
Chen, Y., Ma, N., Pei, Z.-F., Wu, Z., Monte, F. H. D., Keefe, S. H., Yellin, E., Chen, M. S., Yin, J.-C., Lee, G., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.09.003 · Cited by 316 · see citing works
Whiteley, W. N., Slot, K. B., Fernandes, P. M., Sandercock, P. A., & Wardlaw, J. M. (2012) · Stroke · doi:10.1161/strokeaha.112.665331 · Cited by 309 · see citing works
Sequence-specific MR Imaging Findings That Are Useful in Dating Ischemic Stroke
Allen, L. M., Hasso, A. N., Handwerker, J., & Farid, H. (2012) · Radiographics · doi:10.1148/rg.325115760 · Cited by 301 · see citing works
Aspiration Thrombectomy After Intravenous Alteplase Versus Intravenous Alteplase Alone
Mocco, J., Zaidat, O. O., von Kummer, R., Yoo, A. J., Gupta, R. G., Lopes, D. K., Frei, D., Shownkeen, H. N., Budzik, R. F., Ajani, Z. A., et al. (2016) · Stroke · doi:10.1161/strokeaha.116.013372 · Cited by 298 · see citing works
Effectiveness and Safety of Transcranial Laser Therapy for Acute Ischemic Stroke
Zivin, J. A., Albers, G. W., Bornstein, N. M., Chippendale, T. J., Dahlöf, B., Devlin, T. G., Fisher, M., Hacke, W., Holt, W., Ilic, S., et al. (2009) · Stroke · doi:10.1161/strokeaha.109.547547 · Cited by 296 · see citing works
Self-citationUpdate on Treatment of Acute Ischemic Stroke
Rabinstein, A. A. (2020) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000000840 · Cited by 292 · see citing works
Prabhakaran, S., Gonzalez, N. R., Zachrison, K. S., Adeoye, O. M., Alexandrov, A. W., Ansari, S. A., Chapman, S., Czap, A. L., Dumitrascu, O. M., Ishida, K., et al. (2026) · Stroke · doi:10.1161/str.0000000000000513 · Cited by 378 · see citing works
- Authors
- Hacke, W., Kaste, M., Bluhmki, E., Brozman, M., Dávalos, A., Guidetti, D., Larrue, V., Lees, K. R., Medeghri, Z., Machnig, T., Schneider, D., von Kummer, R., Wahlgren, N., & Toni, D.
- Affiliations
- Heidelberg University (DE)
- Helsinki University Hospital (FI)
- Boehringer Ingelheim (Germany) (DE)
- Hospital Universitari Germans Trias i Pujol (ES)
- Ospedaliera di Piacenza (IT)
- Université de Toulouse (FR)
- University of Glasgow (GB)
- Boehringer Ingelheim (France) (FR)
- Leipzig University (DE)
- Karolinska Institutet (SE)
- Sapienza University of Rome (IT)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2008-09-25
- Volume
- 359
- Issue
- 13
- Pages
- 1317-1329
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2159233098
- Cited by
- 6,684
- References
- 23
- Citations by year
- 2026: 275 · 2025: 324 · 2024: 359 · 2023: 301 · 2022: 380 · 2021: 411 · 2020: 381 · 2019: 342 · 2018: 369 · 2017: 334 · 2016: 362 · 2015: 443 · 2014: 409 · 2013: 484 · 2012: 484
- FWCI
- 252.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Institutional Research Information System (University of Udine) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Bristol-Myers Squibb
- Pfizer
- Sanofi
- Les Laboratories Pierre Fabre
- Novo Nordisk
- H. Lundbeck A/S
- Topics
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- alteplase, intravenous thrombolysis, acute ischemic stroke, extended time window, modified Rankin Scale, functional disability, symptomatic intracranial hemorrhage, mortality, treatment safety, stroke treatment efficacy
- MeSH terms
- Acute Disease, Adult, Aged, Brain Ischemia, Double-Blind Method, Drug Administration Schedule, Female, Fibrinolytic Agents, Humans, Infusions, Intravenous, Male, Middle Aged, Tissue Plasminogen Activator, Time Factors, Logistic Models, Odds Ratio, Treatment Outcome, Intracranial Hemorrhages, Stroke
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
