Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke Within 4.5 h: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

<h3>Background</h3><p dir="ltr">Acute ischemic stroke (AIS) requires timely thrombolysis to restore perfusion and minimize neurological damage. Recombinant human prourokinase (rhPro‐UK) has emerged as a promising alternative to alteplase, with potential efficacy and safet...

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Main Author: Muhammad Hassan Waseem (22392178) (author)
Other Authors: Zain Ul Abideen (1410154) (author), Aiman Waheed (22392181) (author), Hafsa Arshad Azam Raja (20151441) (author), Sanan Rasheed (22392184) (author), Muhammad Mukhlis (22392187) (author), Muhammad Abdullah Ali (21409807) (author), Marium Khan (5125439) (author), Umama Alam (21761273) (author), Muhammad Fawad Tahir (22073279) (author), Javed Iqbal (2121922) (author), Ubaid Farooq (22392190) (author), Sania Aimen (22392193) (author)
Published: 2025
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_version_ 1864513537603272704
author Muhammad Hassan Waseem (22392178)
author2 Zain Ul Abideen (1410154)
Aiman Waheed (22392181)
Hafsa Arshad Azam Raja (20151441)
Sanan Rasheed (22392184)
Muhammad Mukhlis (22392187)
Muhammad Abdullah Ali (21409807)
Marium Khan (5125439)
Umama Alam (21761273)
Muhammad Fawad Tahir (22073279)
Javed Iqbal (2121922)
Ubaid Farooq (22392190)
Sania Aimen (22392193)
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author_facet Muhammad Hassan Waseem (22392178)
Zain Ul Abideen (1410154)
Aiman Waheed (22392181)
Hafsa Arshad Azam Raja (20151441)
Sanan Rasheed (22392184)
Muhammad Mukhlis (22392187)
Muhammad Abdullah Ali (21409807)
Marium Khan (5125439)
Umama Alam (21761273)
Muhammad Fawad Tahir (22073279)
Javed Iqbal (2121922)
Ubaid Farooq (22392190)
Sania Aimen (22392193)
author_role author
dc.creator.none.fl_str_mv Muhammad Hassan Waseem (22392178)
Zain Ul Abideen (1410154)
Aiman Waheed (22392181)
Hafsa Arshad Azam Raja (20151441)
Sanan Rasheed (22392184)
Muhammad Mukhlis (22392187)
Muhammad Abdullah Ali (21409807)
Marium Khan (5125439)
Umama Alam (21761273)
Muhammad Fawad Tahir (22073279)
Javed Iqbal (2121922)
Ubaid Farooq (22392190)
Sania Aimen (22392193)
dc.date.none.fl_str_mv 2025-03-13T09:00:00Z
dc.identifier.none.fl_str_mv 10.1002/brb3.70420
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Efficacy_and_Safety_of_Recombinant_Human_Prourokinase_in_Acute_Ischemic_Stroke_Within_4_5_h_A_Systematic_Review_and_Meta_Analysis_of_Randomized_Controlled_Trials/30306145
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Cardiovascular medicine and haematology
Neurosciences
alteplase
ischemic stroke
meta-analysis
recombinant human prourokinase
systematic review
dc.title.none.fl_str_mv Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke Within 4.5 h: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <h3>Background</h3><p dir="ltr">Acute ischemic stroke (AIS) requires timely thrombolysis to restore perfusion and minimize neurological damage. Recombinant human prourokinase (rhPro‐UK) has emerged as a promising alternative to alteplase, with potential efficacy and safety benefits within the critical 4.5‐h treatment window.</p><h3>Methods</h3><p dir="ltr">Electronic databases, including PubMed, ScienceDirect, and Cochrane Central, were comprehensively searched from inception until December 2024. Risk ratios (RRs) with 95% confidence intervals were pooled for the dichotomous outcomes using a random effects model in Review Manager software. The heterogeneity among the included trials was evaluated using the <i>I</i><sup><em>2</em></sup> statistics, and a sensitivity analysis was conducted to investigate the source of heterogeneity.</p><h3>Results</h3><p dir="ltr">The final statistical analysis included 1179 participants in the rhPro‐UK and 1148 in the tPA group. Excellent functional outcome (modified Rankin Scale [mRS] 0‐1) (RR = 1.04, 95% CI: [0.98, 1.10]; <i>p</i> = 0.16) and good functional outcome (mRS 0‐2) (RR = 1.00, 95% CI: [0.96, 1.05]; <i>p</i> = 0.90; <i>I</i><sup><em>2</em></sup> = 0%) were comparable between the two groups. There was also no significant difference in mortality and major neurological improvement. However, there was a trend toward a lower risk of symptomatic intracranial hemorrhage (sICH) in the rhPro‐UK group (RR = 0.53, 95% CI: [0.18, 1.59]; <i>p</i> = 0.26).</p><h3>Conclusion</h3><p dir="ltr">rhPro‐UK demonstrated comparable efficacy to alteplase in achieving functional outcomes in AIS within 4.5 h, with no significant differences in mortality or neurological improvement. Although not statistically significant, a trend toward lower sICH risk with rhPro‐UK highlights its potential safety advantage. More high‐quality randomized clinical trials are required to confirm these findings.</p><h2>Other Information</h2><p dir="ltr">Published in: Brain and Behavior<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1002/brb3.70420" target="_blank">https://dx.doi.org/10.1002/brb3.70420</a></p>
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identifier_str_mv 10.1002/brb3.70420
network_acronym_str Manara2
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oai_identifier_str oai:figshare.com:article/30306145
publishDate 2025
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rights_invalid_str_mv CC BY 4.0
spelling Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke Within 4.5 h: A Systematic Review and Meta‐Analysis of Randomized Controlled TrialsMuhammad Hassan Waseem (22392178)Zain Ul Abideen (1410154)Aiman Waheed (22392181)Hafsa Arshad Azam Raja (20151441)Sanan Rasheed (22392184)Muhammad Mukhlis (22392187)Muhammad Abdullah Ali (21409807)Marium Khan (5125439)Umama Alam (21761273)Muhammad Fawad Tahir (22073279)Javed Iqbal (2121922)Ubaid Farooq (22392190)Sania Aimen (22392193)Biomedical and clinical sciencesCardiovascular medicine and haematologyNeurosciencesalteplaseischemic strokemeta-analysisrecombinant human prourokinasesystematic review<h3>Background</h3><p dir="ltr">Acute ischemic stroke (AIS) requires timely thrombolysis to restore perfusion and minimize neurological damage. Recombinant human prourokinase (rhPro‐UK) has emerged as a promising alternative to alteplase, with potential efficacy and safety benefits within the critical 4.5‐h treatment window.</p><h3>Methods</h3><p dir="ltr">Electronic databases, including PubMed, ScienceDirect, and Cochrane Central, were comprehensively searched from inception until December 2024. Risk ratios (RRs) with 95% confidence intervals were pooled for the dichotomous outcomes using a random effects model in Review Manager software. The heterogeneity among the included trials was evaluated using the <i>I</i><sup><em>2</em></sup> statistics, and a sensitivity analysis was conducted to investigate the source of heterogeneity.</p><h3>Results</h3><p dir="ltr">The final statistical analysis included 1179 participants in the rhPro‐UK and 1148 in the tPA group. Excellent functional outcome (modified Rankin Scale [mRS] 0‐1) (RR = 1.04, 95% CI: [0.98, 1.10]; <i>p</i> = 0.16) and good functional outcome (mRS 0‐2) (RR = 1.00, 95% CI: [0.96, 1.05]; <i>p</i> = 0.90; <i>I</i><sup><em>2</em></sup> = 0%) were comparable between the two groups. There was also no significant difference in mortality and major neurological improvement. However, there was a trend toward a lower risk of symptomatic intracranial hemorrhage (sICH) in the rhPro‐UK group (RR = 0.53, 95% CI: [0.18, 1.59]; <i>p</i> = 0.26).</p><h3>Conclusion</h3><p dir="ltr">rhPro‐UK demonstrated comparable efficacy to alteplase in achieving functional outcomes in AIS within 4.5 h, with no significant differences in mortality or neurological improvement. Although not statistically significant, a trend toward lower sICH risk with rhPro‐UK highlights its potential safety advantage. More high‐quality randomized clinical trials are required to confirm these findings.</p><h2>Other Information</h2><p dir="ltr">Published in: Brain and Behavior<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1002/brb3.70420" target="_blank">https://dx.doi.org/10.1002/brb3.70420</a></p>2025-03-13T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1002/brb3.70420https://figshare.com/articles/journal_contribution/Efficacy_and_Safety_of_Recombinant_Human_Prourokinase_in_Acute_Ischemic_Stroke_Within_4_5_h_A_Systematic_Review_and_Meta_Analysis_of_Randomized_Controlled_Trials/30306145CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/303061452025-03-13T09:00:00Z
spellingShingle Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke Within 4.5 h: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Muhammad Hassan Waseem (22392178)
Biomedical and clinical sciences
Cardiovascular medicine and haematology
Neurosciences
alteplase
ischemic stroke
meta-analysis
recombinant human prourokinase
systematic review
status_str publishedVersion
title Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke Within 4.5 h: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
title_full Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke Within 4.5 h: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
title_fullStr Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke Within 4.5 h: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
title_full_unstemmed Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke Within 4.5 h: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
title_short Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke Within 4.5 h: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
title_sort Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke Within 4.5 h: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
topic Biomedical and clinical sciences
Cardiovascular medicine and haematology
Neurosciences
alteplase
ischemic stroke
meta-analysis
recombinant human prourokinase
systematic review