Comparative Effectiveness of Intravenous Tenecteplase versus Alteplase in Posterior Circulation Ischemic Stroke: A Systematic Review and Meta-Analysis

Comparative Effectiveness of Intravenous Tenecteplase versus Alteplase in Posterior Circulation Ischemic Stroke: A Systematic Review and Meta-Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Comparative Effectiveness of Intravenous Tenecteplase versus Alteplase in Posterior Circulation Ischemic Stroke: A Systematic Review and Meta-Analysis Shaheer bin shafiq This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9389793/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Posterior circulation ischemic stroke (PCIS) is associated with substantial morbidity and mortality, and the optimal intravenous thrombolytic strategy in this subgroup remains unclear. Methods We searched databases for studies comparing intravenous tenecteplase with alteplase in adults with PCIS. Primary outcomes were 90-day functional outcomes (mRS 0–1, mRS 0–2, and mRS 0–3). Secondary outcomes included perfusion, hemorrhagic complications, and mortality. Results Five studies involving 997 patients were included. Tenecteplase was associated with significantly greater likelihood of ambulatory functional outcome at 90 days (mRS 0–3) [RR 1.29, 95% CI 1.03–1.60; p = 0.02] and pre-EVT perfusion [RR 2.18, 95% CI 1.06–4.46; p = 0.03]. No significant differences were observed for excellent functional outcome (mRS 0–1) [RR 1.19, 95% CI 0.91–1.56; p = 0.20], functional independence (mRS 0–2) [RR 1.10, 95% CI 0.89–1.37; p = 0.39], post-EVT perfusion [RR 1.12, 95% CI 0.89–1.40; p = 0.34; I² = 38%], sICH [RR 0.89, 95% CI 0.36–2.22; p = 0.81], any intracranial hemorrhage [RR 1.02, 95% CI 0.59–1.78; p = 0.94], parenchymal hematoma [RR 0.76, 95% CI 0.24–2.38; p = 0.64], or 90-day mortality [RR 0.88, 95% CI 0.66–1.17; p = 0.39]. Conclusion Tenecteplase may improve reperfusion and ambulatory recovery without increasing hemorrhagic complications, mortality compared with alteplase in PCIS, although larger PCIS-specific studies are needed. Clinical Pharmacology Tenecteplase alteplase Posterior circulation ischemic stroke Stroke Reperfusion Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Posterior circulation ischemic stroke (PCIS) which affects the vertebrobasilar arterial territory accounts for roughly one-fifth to one-quarter of ischemic strokes and disproportionately involves the brainstem and cerebellum, with basilar artery occlusion (BAO) carrying especially high morbidity and mortality (including very high fatality in some series) ( 1 ). PCIS poses diagnostic and therapeutic challenges: clinical presentations are heterogeneous and frequently under-recognized, and imaging and reperfusion strategies developed for anterior circulation stroke have limited applicability to vertebrobasilar pathology ( 2 , 3 ). Given the critical function of brainstem structures and the often-catastrophic natural history of BAO, optimizing acute reperfusion therapies in posterior circulation stroke remains a priority for reducing death and long-term disability ( 1 – 3 ). Tenecteplase, a genetically modified tissue plasminogen activator with greater fibrin specificity and a longer half-life, allowing single-bolus administration, has emerged as an attractive alternative to alteplase for intravenous thrombolysis ( 4 ). Recent randomized trials and large pragmatic studies have shown comparable or non-inferior clinical outcomes, improved early reperfusion in selected patients, and similar rates of sICH and mortality for tenecteplase versus alteplase, prompting substantial interest and practice change in many centers ( 4 – 9 ). Nevertheless, many trials enrolled mixed anterior and posterior circulation populations; subgroup analyses specific to vertebrobasilar stroke are limited, and PCIS-specific outcomes such as 90-day mRS, sICH, mortality, and radiographic recanalization remain under-reported or inconsistently defined ( 5 – 8 ). International guideline bodies and expedited recommendations now acknowledge tenecteplase 0.25 mg/kg as a reasonable alternative to alteplase in many settings, particularly for large-vessel occlusion, while also highlighting remaining evidence gaps and heterogeneity across trials and patient subgroups ( 9 , 10 ). A growing number of meta-analyses synthesize recent RCT data, but few focus specifically on PCIS or the vertebrobasilar territory ( 11 ). Accordingly, we performed a systematic review and meta-analysis of adult patients with PCIS confirmed by neuroimaging to compare intravenous tenecteplase with standard-dose intravenous alteplase. This study aims to clarify the comparative efficacy and safety of TNK in a clinically distinct and underexamined stroke population and to inform evidence-based decision-making in PCIS management. 2. Methods This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines ( 12 ). The review protocol was prospectively registered in PROSPERO ID: (CRD420261340568) in order to ensure methodological transparency and rigor. 2.1 Search Strategy: Electronic databases including PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies, covering the period from their inception to 14 February, 2026. The search was designed to identify studies comparing the efficacy and safety of intravenous tenecteplase versus intravenous alteplase in adult patients with PCIS. Both Medical Subject Headings (MeSH) and relevant free-text keywords were used, including “posterior circulation stroke”, “vertebrobasilar stroke”, “basilar artery occlusion”, “acute ischemic stroke”, “tenecteplase”, “TNK”, “alteplase”, “tPA”, “thrombolysis”, “functional independence”, “modified Rankin Scale”, “symptomatic intracranial hemorrhage”, “mortality”, and “recanalization”. Boolean operators were used to combine the search terms appropriately. The detailed search strategy is presented in Supplementary Table S1 . 2.2 Study selection: The articles identified through the comprehensive search were exported to Rayyan AI, and duplicates were removed. Titles and abstracts of the remaining studies were independently reviewed by two authors (M.H and M.J.R), and full-text articles were retrieved for further assessment. The references from all included studies, previous systematic reviews, and meta-analyses were also searched manually for any additional eligible studies. Any discrepancies that arose were resolved by a third author (A.U). There were no restrictions regarding publication date or language. The eligibility criteria for the primary analysis included studies that: ( 1 ) enrolled adult patients aged 18 years or older with acute ischemic stroke involving the posterior circulation or vertebrobasilar territory confirmed by neuroimaging; ( 2 ) compared intravenous tenecteplase at any dose with standard-dose intravenous alteplase; and ( 3 ) reported at least one outcome of interest. We excluded studies based on the following criteria: ( 1 ) pediatric populations; ( 2 ) non-human studies; ( 3 ) case reports, reviews, editorials, letters, conference abstracts without sufficient extractable data, and non-comparative studies; and ( 4 ) failure to report relevant posterior circulation subgroup data or any prespecified outcome. 2.3 Data Extraction and quality assessment: Data from included studies were extracted independently by the two authors (G.T.K and A.U). Author details, study characteristics, study design, country, sample size, patient demographics, baseline clinical characteristics, intervention details, comparator details, and outcome data were extracted onto a predesigned Excel spreadsheet. Any disagreement between the two authors was settled through consultation with the third independent author (S.B.S). Quality assessment of the included studies was conducted independently by two authors (S.B.S and M.M). The Cochrane Risk of Bias tool for randomized trials (RoB 2) was applied to evaluate the methodological quality of randomized controlled trials ( 13 ), while observational studies were assessed using the Newcastle–Ottawa Scale (NOS) ( 14 ). 2.4 Outcomes and Definition: The primary outcomes were 90-day functional outcomes measured by the modified Rankin Scale (mRS), including excellent functional outcome (mRS 0–1), functional independence (mRS 0–2), and ambulatory functional outcome (mRS 0–3), as defined by the individual studies. Secondary efficacy outcomes were successful pre-EVT perfusion and successful post-EVT perfusion, based on study-level definitions of recanalization or reperfusion. Safety outcomes included symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage, any parenchymal hematoma, and 90-day mortality. 2.5 Statistical Analysis: All statistical analyses were conducted using Review Manager (RevMan) version 5.4 (The Nordic Cochrane Centre, Copenhagen). Meta-analyses were performed using a random-effects model, due to anticipated clinical and methodological heterogeneity. Relative risks (RRs) were pooled for binary outcomes (e.g., mRS 0–1, sICH). The I² statistic was used to assess statistical heterogeneity, with values of approximately 25%, 50%, and 75% indicating low, moderate, and high heterogeneity, respectively ( 15 ). 2.6 Certainty of evidence: The certainty of evidence was assessed using the GRADE framework, and a summary of findings table was generated with GRADEpro software ( 16 ). Certainty was evaluated across risk of bias, inconsistency, indirectness, imprecision, and publication bias, with outcomes rated as high, moderate, low or very low certainty 3. Results A visual summary of the study design, key efficacy and safety outcomes, and overall clinical interpretation is provided in the Graphical Abstract. 3.1. Search Results: A total of 710 records were identified through systematic database searches across PubMed, EMBASE and Cochrane CENTRAL. After removing duplicates, 641 records were selected for screening based on the title and abstract. Of these, 634 studies were excluded based on title and abstract review, following which 7 potentially relevant articles were reviewed based on full text. Ultimately, 5 studies met our inclusion criteria. The study selection process is summarized in the PRISMA flow diagram Fig. 1 . 3.2. Study characteristics: Five studies were included in the analysis, comprising a total of 997 adult patients, of whom 449 were assigned to the tenecteplase group and 548 received alteplase. The pooled mean age was approximately 70.5 years in the tenecteplase group and 69.8 years in the alteplase group. Male participants accounted for 243/449 (54.1%) in the tenecteplase group and 324/548 (59.1%) in the alteplase group. Baseline stroke severity, assessed using the National Institutes of Health Stroke Scale (NIHSS), was comparable between groups, with median scores generally ranging from 7 to 20 in the tenecteplase group and 7 to 22 in the alteplase group, reflecting a spectrum from moderate to severe stroke. Diabetes mellitus was reported in selected studies, with proportions ranging from 11% to 18% in the tenecteplase group and 29% to 36% in the alteplase group, indicating a relatively higher burden of diabetes among patients receiving alteplase. The remaining baseline characteristics are presented in Table 1 . Table 1 Baseline and study characteristics Baseline characteristics of included Tenecteplase vs Alteplase studies Values are reported exactly as presented in the source manuscript tables. NR = not reported. Characteristic Alemseged (2021) Bala (2024) Cimflova (2024) Karamchandani (2025) Wolman (2025) TNK tPA TNK tPA TNK tPA TNK tPA TNK tPA Study descriptors Total patients, n 19 91 236 219 59 77 75 88 60 73 Age 77 ± 14 67 ± 14 77 (65–84) 76 (66–84) 72 (65–82) 71 (60–81) 64 (50–72) 66 (57–79) 64 (50–72) 64 (55–78) Male sex, n 10 60 129 116 40 44 35 55 29 49 Baseline NIHSS 20 (5–32) 15 (7–32) 8 ( 5 – 14 ) 8.5 ( 6 – 14 ) 7 ( 4 – 16 ) 7 ( 4 – 12 ) 16 (9–28) 21 (11–26) 19 (11–28) 22 (13–28) Endovascular thrombectomy, n (%) 19 (100) 91 (100) 47 (19.9) 40 (18.3) 12 (20.3) 16 (20.8) 75 (100) 88 (100) 60 (100) 73 (100) Follow-up 90 d 90 d 90–120 d 90–120 d 90 d 90 d 90 d 90 d 90 d 90 d Comorbidities / medical history Hypertension, n (%) 11 (58) 53 (58) NR NR 48 (64.0) 70 (79.5) 38 (63.3) 58 (79.5) Diabetes mellitus, n (%) 2 ( 11 ) 26 (29) NR NR 12 (16.0) 30 (34.1) 11 (18.3) 26 (35.6) Dyslipidemia / hypercholesterolemia, n (%) 7 (37) 25 (27) NR NR 34 (45.3) 54 (61.4) 27 (45.0) 48 (65.8) Atrial fibrillation, n (%) 5 (26) 23 (25) NR NR 18 (24.0) 17 (19.3) 14 (23.3) 14 (19.2) Smoking history, n (%) 1 ( 5 ) 17 ( 19 ) NR NR 30 (40.0) 52 (59.1) 23 (38.3) 44 (60.3) Coronary/cardiac disease, n (%) 4 ( 21 ) 20 ( 22 ) NR NR 13 (17.3) 19 (21.6) 10 (16.7) 16 (21.9) Previous TIA or stroke, n (%) NA NR NR 11 (14.7) 11 (12.5) 9 (15.0) 10 (13.7) Premorbid mRS ≤ 1, n (%) NA NR NR 66 (88.0) 78 (88.6) 54 (90.0) 65 (89.0) Physiology / workflow Systolic blood pressure, mm Hg NA NR NR 150 (135–165) 153 (130–179) 151 (134–169) 150 (129–177) Diastolic blood pressure, mm Hg NA NR NR 84 (74–91) 84 (73–95) 84 (72–94) 83 (73–94) Glucose, mg/dL NA NR NR 133 (111–165) 137 (117–166) 130 (111–166) 137 (120–176) Onset-to-needle time, min 181 (93–203) 160 (130–200) 136 (98–190) 130 (95–191) 136 (100–213) 141 (108–197) NR 124 (97–182) 138 (103–201) Needle-to-puncture / onset-to-puncture, min 48 (40–71) 110 (51–185) 85 (66–117) 91 (63–113) 269 (152–355)* 174 (142–328)* NR 78 (45–136) 94 (56–161) Notes TNK : Tenecteplase, tPA : Alteplase, NA : Not applicable, NR : Not reported. 1. Values are reproduced from manuscript baseline tables/subgroup tables used for extraction. 3.3. Quality Assessment: The risk of bias assessment demonstrated overall favorable methodological quality among the included studies. Among the three included randomized trials, all have a low overall risk of bias across the evaluated domains according to the ROB2 Tool Supplementary Table 2 . Notably, while data from post hoc studies were utilized for the pooled quantitative analyses, the risk of bias was assessed using their respective original, primary trials. For observational studies assessed using the NOS methodological quality ranged from 7 to 9 stars, indicating moderate to high quality. Overall, the included evidence demonstrated adequate methodological rigor with no major concerns identified in the quality assessment Supplementary Table 3 . 3.4. Primary Outcomes: 3.4.1. mRS 0–1: Regarding excellent recovery, findings favored tenecteplase over alteplase, though the difference failed to reach statistical significance (RR 1.19, 95% CI 0.91–1.56; p = 0.20; I² = 0%). This magnitude suggests a potential trend towards better recovery, pointing to a possible clinical advantage Fig. 2 . 3.4.2. mRS 0–2: Patients in both groups demonstrated comparable good functional outcomes, with no statistically significant difference observed (RR 1.10, 95% CI 0.89–1.37; p = 0.39; I² = 40%). The effect size suggests similar efficacy, pointing to tenecteplase performing on par with alteplase Fig. 3 . 3.4.3. (mRS 0–3): Tenecteplase was associated with a statistically significant improvement in ambulatory functional outcomes, as patients achieved this milestone more frequently than those receiving alteplase (RR 1.29, 95% CI 1.03–1.60; p = 0.02; I² = 0%). The magnitude of the effect suggests a substantial benefit in patient mobility, pointing to a distinct clinical advantage for tenecteplase Fig. 4 . 3.5. Secondary Outcomes: 3.5.1. Pre-EVT perfusion: A statistically significant increase in successful pre-EVT perfusion was observed in the tenecteplase group (RR 2.18, 95% CI 1.06–4.46; p = 0.03; I² = 23%). This magnitude suggests a substantial benefit in early recanalization, pointing to a strong clinical advantage for tenecteplase Fig. 5 . 3.5.2. Post-EVT perfusion: Following endovascular therapy, post-EVT perfusion success rates were comparable between the two treatments, failing to reach statistical significance (RR 1.12, 95% CI 0.89–1.40; p = 0.34; I² = 38%). This suggests similar final reperfusion efficacy, pointing to equivalent clinical performance after intervention Supplementary Fig. 1. 3.6. Safety outcomes: 3.6.1. Symptomatic intracranial hemorrhage (SICH): Evaluating safety, the incidence of sICH was similar across groups and failed to reach statistical significance (RR 0.89, 95% CI 0.36–2.22; p = 0.81; I² = 0%). The effect size suggests a statistically equivalent risk, pointing to tenecteplase offering a safety profile comparable to alteplase Supplementary Fig. 2. 3.6.2. Any intracranial hemorrhage: Rates of any intracranial hemorrhage were nearly identical between tenecteplase and alteplase, with no significant difference found (RR 1.02, 95% CI 0.59–1.78; p = 0.94; I² = 0%). The magnitude suggests no meaningful difference in overall bleeding risk, pointing to a non-inferior clinical safety profile Supplementary Fig. 3. 3.6.3. Any parenchymal hematoma: A slight reduction in parenchymal hematoma risk favored tenecteplase, although the results failed to reach statistical significance (RR 0.76, 95% CI 0.24–2.38; p = 0.64; I² = 0%). This magnitude suggests a potential trend toward decreased severe bleeding, pointing to a comparable clinical safety profile Supplementary Fig. 4. 3.6.4. 90-day mortality : Finally, 90-day mortality rates favored tenecteplase slightly, but the findings remained statistically equivalent (RR 0.88, 95% CI 0.66–1.17; p = 0.39; I² = 0%). The magnitude suggests a possible survival benefit, pointing to a comparable overall survival profile at 90 days. Supplementary Fig. 5. 3.7. Certainty of Evidence: The certainty of evidence for each outcome was evaluated using the GRADE approach. The certainty of evidence was rated as moderate for functional outcomes (mRS 0–3, mRS 0–2, mRS 0–1), pre- and post-EVT perfusion, any intracranial hemorrhage, and 90-day mortality, primarily due to concerns related to imprecision. In contrast, the certainty of evidence was judged to be low for sICH and any parenchymal hematoma due to very serious imprecision driven by wide confidence intervals and low event rates. Overall, these findings indicate that confidence in the pooled estimates ranged from low to moderate across all assessed outcomes. The detailed summary of findings is provided in Supplementary Table 4 . 4. Discussion Ischemic stroke of the posterior circulation accounts for a substantial proportion of strokes and is associated with high morbidity and mortality due to brainstem involvement and large vessel occlusion. Most thrombolytic trials have focused primarily on anterior circulation strokes, leaving uncertainty about the optimal intravenous thrombolytic strategy for posterior circulation stroke. In this meta-analysis, we specifically evaluated the comparative effectiveness of intravenous tenecteplase versus alteplase in patients with PCIS, thereby providing a focused synthesis of posterior circulation–specific functional, perfusion, and safety outcomes. In this meta-analysis, we pooled evidence from five studies, including randomized and observational/post hoc posterior circulation data. Overall, tenecteplase was associated with a 29% higher likelihood of achieving an ambulatory functional outcome at 90 days (mRS 0–3) compared with alteplase. For excellent (mRS 0–1) and good (mRS 0–2) functional outcomes, results favored tenecteplase; however, these differences did not reach statistical significance. Pre-EVT perfusion was more than twice as likely in the tenecteplase group, suggesting a potential advantage in early reperfusion. In contrast, post-EVT perfusion outcomes were comparable between groups, indicating similar final reperfusion success following intervention. Importantly, safety outcomes including sICH, any intracranial hemorrhage, parenchymal hematoma, and 90-day mortality—were broadly similar between groups, with no meaningful increase in bleeding or mortality observed, although several estimates remain imprecise due to low event rates. Compared with currently used thrombolytic strategies, tenecteplase offers several practical and pharmacologic advantages over alteplase in the treatment of acute ischemic stroke. Tenecteplase is a bioengineered variant of tissue plasminogen activator with amino acid substitutions that confer greater fibrin specificity, increased resistance to inhibition by plasminogen activator inhibitor‑1 (PAI‑1), and a significantly longer plasma half‑life than alteplase. These properties permit single‑bolus intravenous administration, rather than the bolus plus continuous infusion required for alteplase, and simplify preparation and dosing in emergency settings, potentially reducing workflow delays and medication errors ( 17 , 18 ). These mechanistic and workflow advantages may partly explain the observed association with higher pre-EVT perfusion and better ambulatory recovery in the present analysis. Many observational cohort studies have shown that tenecteplase is associated with significantly shorter door‑to‑needle and door‑to‑puncture times and a higher likelihood of meeting target acute stroke treatment benchmarks, as well as greater early neurological improvement at 24 hours, without increasing the risk of symptomatic or any intracranial hemorrhage compared with alteplase in routine clinical use ( 19 , 20 ). A real‑world analysis by Maxhuni et al., reported similar early clinical outcomes and safety profiles (including sICH and functional status at discharge) between tenecteplase and alteplase during the initial implementation of tenecteplase in a stroke center, supporting its effectiveness and tolerability outside of controlled trials ( 21 ). Moreover, large multicenter registry data from the CERTAIN collaboration by Warach et al., demonstrated that tenecteplase use in routine clinical practice was associated with significantly lower odds of sICH than alteplase, reinforcing confidence in its safety profile in unselected AIS patients ( 22 ). Beyond the functional and safety outcomes highlighted earlier, additional clinical evidence further supports the potential role of tenecteplase as a viable alternative to alteplase in AIS. Several larger meta‑analyses and systematic reviews have examined aggregated data from randomized trials and observational studies. However, these broader AIS findings should be interpreted cautiously when applied to posterior circulation stroke, because vertebrobasilar occlusion has distinct pathophysiologic and prognostic features and remains underrepresented in most thrombolysis datasets. A recent meta‑analysis by Shen et al., included over 7,508 patients across 16 randomized controlled trials found that tenecteplase was not inferior to alteplase for early thrombolytic therapy and even demonstrated advantages in early neurological improvement and vessel recanalization, without significant differences in safety outcomes such as sICH or mortality ( 23 ). Moreover, a systematic review pooling nine RCTs reported comparable rates of functional independence and 90‑day mortality between tenecteplase and alteplase, while indicating trends toward greater early neurological recovery with tenecteplase, although statistical significance varied across outcomes ( 24 ). Our findings are directionally consistent with these broader analyses, but add more specific insight into the posterior circulation subgroup. Taken together, these findings suggest that tenecteplase may offer an early reperfusion and ambulatory recovery advantage in PCIS, but the overall certainty of evidence remains limited and definitive superiority over alteplase cannot yet be concluded. Limitations : This meta-analysis has several limitations that should be acknowledged. First, only five studies with a total of 997 patients were included, which limits the overall statistical power and may reduce the generalizability of the findings. Second, the pooled evidence was derived from a mixture of randomized and observational data, which may introduce methodological heterogeneity despite acceptable quality assessment results. Third, some of the included studies were not originally designed exclusively for PCIS, and or circulation data were extracted from subgroup analyses, which may weaken the strength of conclusions specific to this population. In addition, outcome definitions and reporting were not entirely uniform across studies, particularly for perfusion and recanalization-related endpoints, which may have affected comparability between studies. Differences in treatment workflows, including onset-to-needle time, EVT use, and institutional stroke protocols, may also have influenced outcomes. Furthermore, several safety endpoints such as sICH and parenchymal hematoma were based on low event rates, resulting in wide confidence intervals and limiting precision. Finally, the analysis relied on study-level rather than individual patient-level data, which restricted more detailed subgroup analyses according to stroke severity, occlusion site, thrombolytic dose, and timing of reperfusion therapy. 5. Conclusion 5. Conclusion : In patients with PCIS, intravenous tenecteplase was associated with improved ambulatory functional outcome (mRS 0–3) and higher pre-EVT perfusion compared with alteplase, while other functional, perfusion, and safety outcomes were broadly similar between treatments. These findings suggest that tenecteplase may be an effective and safe alternative to alteplase in this subgroup. However, the evidence remains limited by small sample size, inclusion of mixed study designs, and low event rates for several safety endpoints. Larger posterior circulation–specific prospective studies are needed to confirm whether the apparent early reperfusion and ambulatory outcome advantages of tenecteplase translate into consistent long-term clinical benefit. Declarations Scientific Category: Original Research Institutional review board approval and ethics committee clearance/Ethics approval: Not required Patient consent: Not required Availability of data and materials: The data supporting the findings of this study were obtained from published studies. The data and material used were publicly available . Declaration of Conflicting Interests: None Clinical Trial Number : Not applicable Acknowledgments: None Funding: None received Authors' contributions: Conception and design of the study: S.B.S, M.A, M.M Analysis and interpretation of data: M.H, M.J.R Collection or assembly of data: M.H, G.T.K Drafting or revising the article : A.U, A.A.U Final approval of the version to be published: U.A, H.A References Schneider AM, Neuhaus AA, Hadley G, Balami JS, Harston GW, DeLuca GC et al (2023) Posterior circulation ischaemic stroke diagnosis and management. 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BMJ 327(7414):557–560. 10.1136/bmj.327.7414.557 PubMed PMID: 12958120 Zhang Y, Akl EA, Schünemann HJ (2019) Using systematic reviews in guideline development: the GRADE approach. Res Synth Methods 10(3):312–329. 10.1002/jrsm.1313 PubMed PMID: 30006970 Miranda SG, Ofoegbuna I, Tran M, Jutba AS, Vo C (2025) Evaluating the Safety of Tenecteplase Versus Alteplase for Acute Ischemic Stroke. Emergency Care and Medicine. Vol 2, Page 37. 2025;2(3):37. 10.3390/ecm2030037 Kobeissi H, Ghozy S, Turfe B, Bilgin C, Kadirvel R, Kallmes DF et al (2023) Tenecteplase vs. alteplase for treatment of acute ischemic stroke: A systematic review and meta-analysis of randomized trials. Front Neurol 14. 10.3389/fneur.2023.1102463 PubMed PMID: 36756249 Yao Y, Wu Y, Zhang X, Liu C, Cai L, Ying Y et al (2024) Real-world data of tenecteplase vs. alteplase in the treatment of acute ischemic stroke: a single-center analysis. Front Neurol 15:1386386. 10.3389/fneur.2024.1386386 Henderson B, Emborski R, Diioia A, Stone D, Stupca K (2025) Improved Door-to-Needle Time After Implementation of Tenecteplase as the Preferred Thrombolytic for Acute Ischemic Stroke at a Large Community Teaching Hospital Emergency Department. Hosp Pharm 60(1):90–96 doi:10.1177/00185787241289296 PubMed PMID: 39544831 Maxhuni T, Culaj F, Sayar MM, Böttger P, Hamzic S, Gerner ST et al (2026) 26:1 Comparative effectiveness of Tenecteplase and Alteplase for ischemic stroke: real-world data from a stroke center. BMC Neurology 2026;26(1):59-. 10.1186/s12883-026-04655-5 PubMed PMID: 41572186 Warach SJ, Ranta A, Kim J, Song SS, Wallace A, Beharry J et al (2023) Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) Collaboration. JAMA Neurol 80(7):732–738. 10.1001/jamaneurol.2023.1449 PubMed PMID: 37252708 Shen Z, Bao N, Tang M, Yang Y, Li J, Liu W et al (2023) Tenecteplase vs. Alteplase for Intravenous Thrombolytic Therapy of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis. Neurol Ther 12(5):1553. 10.1007/s40120-023-00530-4 PubMed PMID: 37552459 Singh A, Singh MP, Gaikwad NR, Kannauje PK (2024) Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Systematic Review and Meta-analysis. Ann Neurosci 31(2):132–142. 10.1177/09727531231193242 Additional Declarations The authors declare no competing interests. Supplementary Files image1.png Graphical Abstract: Visual summary of the comparative efficacy and safety of intravenous tenecteplase versus alteplase in posterior circulation ischemic stroke. SupplementaryfileTNKvsALP.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9389793","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":621497275,"identity":"fbdfd0ee-cd1d-4bee-a37e-25bf5a4d1f40","order_by":0,"name":"Shaheer bin shafiq","email":"data:image/png;base64,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","orcid":"","institution":"dow university of health sciences","correspondingAuthor":true,"prefix":"","firstName":"Shaheer","middleName":"bin","lastName":"shafiq","suffix":""}],"badges":[],"createdAt":"2026-04-11 17:38:45","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-9389793/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9389793/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106903627,"identity":"ea2a4e8a-eb35-45d1-90f4-e5b82637a440","added_by":"auto","created_at":"2026-04-14 15:12:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":35429,"visible":true,"origin":"","legend":"\u003cp\u003ePrisma Flowchart\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-9389793/v1/777de0d7ada5110547204474.png"},{"id":106903629,"identity":"6560f153-e988-478f-8119-6f3df648a7f9","added_by":"auto","created_at":"2026-04-14 15:12:19","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":9927,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot comparing the likelihood of achieving an excellent functional outcome (mRS 0–1) at 90 days.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-9389793/v1/8d3743e65a14c1c18344c3bb.png"},{"id":106903626,"identity":"d790f4b7-0700-4dbf-95b5-793203438f99","added_by":"auto","created_at":"2026-04-14 15:12:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":10425,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot evaluating good functional outcomes (mRS 0–2) at 90 days for both drugs.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-9389793/v1/2c4b1065c1a1e1420321b2ee.png"},{"id":106903679,"identity":"818464e9-54ac-4ec2-a2db-2f89877debed","added_by":"auto","created_at":"2026-04-14 15:12:28","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":8972,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot showing the likelihood of achieving an ambulatory functional outcome (mRS 0–3) at 90 days for Tenecteplase vs Alteplase.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-9389793/v1/6c63d66f8b17187e81193a24.png"},{"id":106903688,"identity":"97ca9649-3fcc-4f04-a7df-189111dab97a","added_by":"auto","created_at":"2026-04-14 15:12:30","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":10059,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot comparing the rate of successful pre-EVT perfusion between Tenecteplase and Alteplase.\u003c/p\u003e","description":"","filename":"image6.png","url":"https://assets-eu.researchsquare.com/files/rs-9389793/v1/140f6fd8ec761df47c69131b.png"},{"id":106903765,"identity":"0f8d475c-d7dc-4725-b8e4-32a036b864ec","added_by":"auto","created_at":"2026-04-14 15:12:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1233541,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9389793/v1/723722b7-f761-4652-9d5c-422fc10bcf55.pdf"},{"id":106903677,"identity":"1e38f13b-c4bc-4b86-b898-3aff63c1754b","added_by":"auto","created_at":"2026-04-14 15:12:27","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":3488166,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraphical Abstract: \u003c/strong\u003eVisual summary of the comparative efficacy and safety of intravenous tenecteplase versus alteplase in posterior circulation ischemic stroke.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-9389793/v1/166b3094e29c9fb0f0b665dc.png"},{"id":106903698,"identity":"57f6d551-ec30-4e22-9b27-b747d48b7fe6","added_by":"auto","created_at":"2026-04-14 15:12:33","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":444777,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryfileTNKvsALP.docx","url":"https://assets-eu.researchsquare.com/files/rs-9389793/v1/a3d98fb1c8e4d5b8a71c9bce.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eComparative Effectiveness of Intravenous Tenecteplase versus Alteplase in Posterior Circulation Ischemic Stroke: A Systematic Review and Meta-Analysis\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003ePosterior circulation ischemic stroke (PCIS) which affects the vertebrobasilar arterial territory accounts for roughly one-fifth to one-quarter of ischemic strokes and disproportionately involves the brainstem and cerebellum, with basilar artery occlusion (BAO) carrying especially high morbidity and mortality (including very high fatality in some series) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). PCIS poses diagnostic and therapeutic challenges: clinical presentations are heterogeneous and frequently under-recognized, and imaging and reperfusion strategies developed for anterior circulation stroke have limited applicability to vertebrobasilar pathology (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Given the critical function of brainstem structures and the often-catastrophic natural history of BAO, optimizing acute reperfusion therapies in posterior circulation stroke remains a priority for reducing death and long-term disability (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTenecteplase, a genetically modified tissue plasminogen activator with greater fibrin specificity and a longer half-life, allowing single-bolus administration, has emerged as an attractive alternative to alteplase for intravenous thrombolysis (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Recent randomized trials and large pragmatic studies have shown comparable or non-inferior clinical outcomes, improved early reperfusion in selected patients, and similar rates of sICH and mortality for tenecteplase versus alteplase, prompting substantial interest and practice change in many centers (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Nevertheless, many trials enrolled mixed anterior and posterior circulation populations; subgroup analyses specific to vertebrobasilar stroke are limited, and PCIS-specific outcomes such as 90-day mRS, sICH, mortality, and radiographic recanalization remain under-reported or inconsistently defined (\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eInternational guideline bodies and expedited recommendations now acknowledge tenecteplase 0.25 mg/kg as a reasonable alternative to alteplase in many settings, particularly for large-vessel occlusion, while also highlighting remaining evidence gaps and heterogeneity across trials and patient subgroups (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). A growing number of meta-analyses synthesize recent RCT data, but few focus specifically on PCIS or the vertebrobasilar territory (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Accordingly, we performed a systematic review and meta-analysis of adult patients with PCIS confirmed by neuroimaging to compare intravenous tenecteplase with standard-dose intravenous alteplase. This study aims to clarify the comparative efficacy and safety of TNK in a clinically distinct and underexamined stroke population and to inform evidence-based decision-making in PCIS management.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eThis meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The review protocol was prospectively registered in PROSPERO ID: (CRD420261340568) in order to ensure methodological transparency and rigor.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Search Strategy:\u003c/h2\u003e \u003cp\u003eElectronic databases including PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies, covering the period from their inception to 14 February, 2026. The search was designed to identify studies comparing the efficacy and safety of intravenous tenecteplase versus intravenous alteplase in adult patients with PCIS. Both Medical Subject Headings (MeSH) and relevant free-text keywords were used, including \u0026ldquo;posterior circulation stroke\u0026rdquo;, \u0026ldquo;vertebrobasilar stroke\u0026rdquo;, \u0026ldquo;basilar artery occlusion\u0026rdquo;, \u0026ldquo;acute ischemic stroke\u0026rdquo;, \u0026ldquo;tenecteplase\u0026rdquo;, \u0026ldquo;TNK\u0026rdquo;, \u0026ldquo;alteplase\u0026rdquo;, \u0026ldquo;tPA\u0026rdquo;, \u0026ldquo;thrombolysis\u0026rdquo;, \u0026ldquo;functional independence\u0026rdquo;, \u0026ldquo;modified Rankin Scale\u0026rdquo;, \u0026ldquo;symptomatic intracranial hemorrhage\u0026rdquo;, \u0026ldquo;mortality\u0026rdquo;, and \u0026ldquo;recanalization\u0026rdquo;. Boolean operators were used to combine the search terms appropriately. The detailed search strategy is presented in \u003cb\u003eSupplementary Table S1\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Study selection:\u003c/h2\u003e \u003cp\u003eThe articles identified through the comprehensive search were exported to Rayyan AI, and duplicates were removed. Titles and abstracts of the remaining studies were independently reviewed by two authors (M.H and M.J.R), and full-text articles were retrieved for further assessment. The references from all included studies, previous systematic reviews, and meta-analyses were also searched manually for any additional eligible studies. Any discrepancies that arose were resolved by a third author (A.U). There were no restrictions regarding publication date or language. The eligibility criteria for the primary analysis included studies that: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) enrolled adult patients aged 18 years or older with acute ischemic stroke involving the posterior circulation or vertebrobasilar territory confirmed by neuroimaging; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) compared intravenous tenecteplase at any dose with standard-dose intravenous alteplase; and (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) reported at least one outcome of interest. We excluded studies based on the following criteria: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) pediatric populations; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) non-human studies; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) case reports, reviews, editorials, letters, conference abstracts without sufficient extractable data, and non-comparative studies; and (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) failure to report relevant posterior circulation subgroup data or any prespecified outcome.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Data Extraction and quality assessment:\u003c/h2\u003e \u003cp\u003eData from included studies were extracted independently by the two authors (G.T.K and A.U). Author details, study characteristics, study design, country, sample size, patient demographics, baseline clinical characteristics, intervention details, comparator details, and outcome data were extracted onto a predesigned Excel spreadsheet. Any disagreement between the two authors was settled through consultation with the third independent author (S.B.S). Quality assessment of the included studies was conducted independently by two authors (S.B.S and M.M). The Cochrane Risk of Bias tool for randomized trials (RoB 2) was applied to evaluate the methodological quality of randomized controlled trials (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), while observational studies were assessed using the Newcastle\u0026ndash;Ottawa Scale (NOS) (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Outcomes and Definition:\u003c/h2\u003e \u003cp\u003eThe primary outcomes were 90-day functional outcomes measured by the modified Rankin Scale (mRS), including excellent functional outcome (mRS 0\u0026ndash;1), functional independence (mRS 0\u0026ndash;2), and ambulatory functional outcome (mRS 0\u0026ndash;3), as defined by the individual studies. Secondary efficacy outcomes were successful pre-EVT perfusion and successful post-EVT perfusion, based on study-level definitions of recanalization or reperfusion. Safety outcomes included symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage, any parenchymal hematoma, and 90-day mortality.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical Analysis:\u003c/h2\u003e \u003cp\u003eAll statistical analyses were conducted using Review Manager (RevMan) version 5.4 (The Nordic Cochrane Centre, Copenhagen). Meta-analyses were performed using a random-effects model, due to anticipated clinical and methodological heterogeneity. Relative risks (RRs) were pooled for binary outcomes (e.g., mRS 0\u0026ndash;1, sICH). The I\u0026sup2; statistic was used to assess statistical heterogeneity, with values of approximately 25%, 50%, and 75% indicating low, moderate, and high heterogeneity, respectively (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Certainty of evidence:\u003c/h2\u003e \u003cp\u003eThe certainty of evidence was assessed using the GRADE framework, and a summary of findings table was generated with GRADEpro software (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Certainty was evaluated across risk of bias, inconsistency, indirectness, imprecision, and publication bias, with outcomes rated as high, moderate, low or very low certainty\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eA visual summary of the study design, key efficacy and safety outcomes, and overall clinical interpretation is provided in the \u003cb\u003eGraphical Abstract.\u003c/b\u003e\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Search Results:\u003c/h2\u003e \u003cp\u003eA total of 710 records were identified through systematic database searches across PubMed, EMBASE and Cochrane CENTRAL. After removing duplicates, 641 records were selected for screening based on the title and abstract. Of these, 634 studies were excluded based on title and abstract review, following which 7 potentially relevant articles were reviewed based on full text. Ultimately, 5 studies met our inclusion criteria. The study selection process is summarized in the PRISMA flow diagram Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Study characteristics:\u003c/h2\u003e \u003cp\u003eFive studies were included in the analysis, comprising a total of 997 adult patients, of whom 449 were assigned to the tenecteplase group and 548 received alteplase. The pooled mean age was approximately 70.5 years in the tenecteplase group and 69.8 years in the alteplase group. Male participants accounted for 243/449 (54.1%) in the tenecteplase group and 324/548 (59.1%) in the alteplase group. Baseline stroke severity, assessed using the National Institutes of Health Stroke Scale (NIHSS), was comparable between groups, with median scores generally ranging from 7 to 20 in the tenecteplase group and 7 to 22 in the alteplase group, reflecting a spectrum from moderate to severe stroke. Diabetes mellitus was reported in selected studies, with proportions ranging from 11% to 18% in the tenecteplase group and 29% to 36% in the alteplase group, indicating a relatively higher burden of diabetes among patients receiving alteplase. The remaining baseline characteristics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline and study characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eBaseline characteristics of included Tenecteplase vs Alteplase studies\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eValues are reported exactly as presented in the source manuscript tables. NR\u0026thinsp;=\u0026thinsp;not reported.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCharacteristic\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAlemseged (2021)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e\u003cb\u003eBala (2024)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e\u003cb\u003eCimflova (2024)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e\u003cb\u003eKaramchandani (2025)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e\u003cb\u003eWolman (2025)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTNK\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003etPA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eTNK\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003etPA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eTNK\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003etPA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eTNK\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003etPA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003eTNK\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003etPA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eStudy descriptors\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal patients, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e236\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e219\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e77 (65\u0026ndash;84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76 (66\u0026ndash;84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e72 (65\u0026ndash;82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e71 (60\u0026ndash;81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e64 (50\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e66 (57\u0026ndash;79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e64 (50\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e64 (55\u0026ndash;78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e129\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline NIHSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (5\u0026ndash;32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (7\u0026ndash;32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.5 (\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11 CR12 CR13\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16 (9\u0026ndash;28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e21 (11\u0026ndash;26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e19 (11\u0026ndash;28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e22 (13\u0026ndash;28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndovascular thrombectomy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (19.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12 (20.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16 (20.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e75 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e88 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e60 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e73 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90\u0026ndash;120 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90\u0026ndash;120 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e90 d\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eComorbidities / medical history\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e48 (64.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e70 (79.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e38 (63.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e58 (79.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12 (16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e30 (34.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e11 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e26 (35.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyslipidemia / hypercholesterolemia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e34 (45.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e54 (61.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e27 (45.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e48 (65.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrial fibrillation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e18 (24.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e17 (19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e14 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e14 (19.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking history, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e52 (59.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e23 (38.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e44 (60.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoronary/cardiac disease, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e13 (17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e19 (21.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e10 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e16 (21.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious TIA or stroke, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11 (14.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e11 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e9 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e10 (13.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePremorbid mRS\u0026thinsp;\u0026le;\u0026thinsp;1, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e66 (88.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e78 (88.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54 (90.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e65 (89.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003ePhysiology / workflow\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystolic blood pressure, mm Hg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e150 (135\u0026ndash;165)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e153 (130\u0026ndash;179)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e151 (134\u0026ndash;169)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e150 (129\u0026ndash;177)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiastolic blood pressure, mm Hg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e84 (74\u0026ndash;91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e84 (73\u0026ndash;95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e84 (72\u0026ndash;94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e83 (73\u0026ndash;94)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucose, mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e133 (111\u0026ndash;165)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e137 (117\u0026ndash;166)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e130 (111\u0026ndash;166)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e137 (120\u0026ndash;176)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOnset-to-needle time, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e181 (93\u0026ndash;203)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e160 (130\u0026ndash;200)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e136 (98\u0026ndash;190)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e130 (95\u0026ndash;191)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e136 (100\u0026ndash;213)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e141 (108\u0026ndash;197)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e124 (97\u0026ndash;182)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e138 (103\u0026ndash;201)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeedle-to-puncture / onset-to-puncture, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (40\u0026ndash;71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110 (51\u0026ndash;185)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85 (66\u0026ndash;117)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e91 (63\u0026ndash;113)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e269 (152\u0026ndash;355)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e174 (142\u0026ndash;328)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e78 (45\u0026ndash;136)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e94 (56\u0026ndash;161)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eNotes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTNK\u003c/b\u003e: Tenecteplase, \u003cb\u003etPA\u003c/b\u003e: Alteplase, \u003cb\u003eNA\u003c/b\u003e: Not applicable, \u003cb\u003eNR\u003c/b\u003e: Not reported.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003e1. Values are reproduced from manuscript baseline tables/subgroup tables used for extraction.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Quality Assessment:\u003c/h2\u003e \u003cp\u003eThe risk of bias assessment demonstrated overall favorable methodological quality among the included studies. Among the three included randomized trials, all have a low overall risk of bias across the evaluated domains according to the ROB2 Tool \u003cb\u003eSupplementary Table\u0026nbsp;2\u003c/b\u003e. Notably, while data from \u003cem\u003epost hoc\u003c/em\u003e studies were utilized for the pooled quantitative analyses, the risk of bias was assessed using their respective original, primary trials. For observational studies assessed using the NOS methodological quality ranged from 7 to 9 stars, indicating moderate to high quality. Overall, the included evidence demonstrated adequate methodological rigor with no major concerns identified in the quality assessment \u003cb\u003eSupplementary Table\u0026nbsp;3\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Primary Outcomes:\u003c/h2\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003e3.4.1. mRS 0\u0026ndash;1:\u003c/h2\u003e \u003cp\u003eRegarding excellent recovery, findings favored tenecteplase over alteplase, though the difference failed to reach statistical significance (RR 1.19, 95% CI 0.91\u0026ndash;1.56; p\u0026thinsp;=\u0026thinsp;0.20; I\u0026sup2; = 0%). This magnitude suggests a potential trend towards better recovery, pointing to a possible clinical advantage Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003e3.4.2. mRS 0\u0026ndash;2:\u003c/h2\u003e \u003cp\u003ePatients in both groups demonstrated comparable good functional outcomes, with no statistically significant difference observed (RR 1.10, 95% CI 0.89\u0026ndash;1.37; p\u0026thinsp;=\u0026thinsp;0.39; I\u0026sup2; = 40%). The effect size suggests similar efficacy, pointing to tenecteplase performing on par with alteplase Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003e3.4.3. (mRS 0\u0026ndash;3):\u003c/h2\u003e \u003cp\u003eTenecteplase was associated with a statistically significant improvement in ambulatory functional outcomes, as patients achieved this milestone more frequently than those receiving alteplase (RR 1.29, 95% CI 1.03\u0026ndash;1.60; p\u0026thinsp;=\u0026thinsp;0.02; I\u0026sup2; = 0%). The magnitude of the effect suggests a substantial benefit in patient mobility, pointing to a distinct clinical advantage for tenecteplase Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e3.5. Secondary Outcomes:\u003c/h2\u003e \u003cdiv id=\"Sec18\" class=\"Section3\"\u003e \u003ch2\u003e3.5.1. Pre-EVT perfusion:\u003c/h2\u003e \u003cp\u003eA statistically significant increase in successful pre-EVT perfusion was observed in the tenecteplase group (RR 2.18, 95% CI 1.06\u0026ndash;4.46; p\u0026thinsp;=\u0026thinsp;0.03; I\u0026sup2; = 23%). This magnitude suggests a substantial benefit in early recanalization, pointing to a strong clinical advantage for tenecteplase Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section3\"\u003e \u003ch2\u003e3.5.2. Post-EVT perfusion:\u003c/h2\u003e \u003cp\u003eFollowing endovascular therapy, post-EVT perfusion success rates were comparable between the two treatments, failing to reach statistical significance (RR 1.12, 95% CI 0.89\u0026ndash;1.40; p\u0026thinsp;=\u0026thinsp;0.34; I\u0026sup2; = 38%). This suggests similar final reperfusion efficacy, pointing to equivalent clinical performance after intervention \u003cb\u003eSupplementary Fig.\u0026nbsp;1.\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e3.6. Safety outcomes:\u003c/h2\u003e \u003cdiv id=\"Sec21\" class=\"Section3\"\u003e \u003ch2\u003e3.6.1. Symptomatic intracranial hemorrhage (SICH):\u003c/h2\u003e \u003cp\u003eEvaluating safety, the incidence of sICH was similar across groups and failed to reach statistical significance (RR 0.89, 95% CI 0.36\u0026ndash;2.22; p\u0026thinsp;=\u0026thinsp;0.81; I\u0026sup2; = 0%). The effect size suggests a statistically equivalent risk, pointing to tenecteplase offering a safety profile comparable to alteplase \u003cb\u003eSupplementary Fig.\u0026nbsp;2.\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section3\"\u003e \u003ch2\u003e3.6.2. Any intracranial hemorrhage:\u003c/h2\u003e \u003cp\u003eRates of any intracranial hemorrhage were nearly identical between tenecteplase and alteplase, with no significant difference found (RR 1.02, 95% CI 0.59\u0026ndash;1.78; p\u0026thinsp;=\u0026thinsp;0.94; I\u0026sup2; = 0%). The magnitude suggests no meaningful difference in overall bleeding risk, pointing to a non-inferior clinical safety profile \u003cb\u003eSupplementary Fig.\u0026nbsp;3.\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003e3.6.3. Any parenchymal hematoma:\u003c/h2\u003e \u003cp\u003eA slight reduction in parenchymal hematoma risk favored tenecteplase, although the results failed to reach statistical significance (RR 0.76, 95% CI 0.24\u0026ndash;2.38; p\u0026thinsp;=\u0026thinsp;0.64; I\u0026sup2; = 0%). This magnitude suggests a potential trend toward decreased severe bleeding, pointing to a comparable clinical safety profile \u003cb\u003eSupplementary Fig.\u0026nbsp;4.\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section3\"\u003e \u003ch2\u003e\u003cb\u003e3.6.4. 90-day mortality\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eFinally, 90-day mortality rates favored tenecteplase slightly, but the findings remained statistically equivalent (RR 0.88, 95% CI 0.66\u0026ndash;1.17; p\u0026thinsp;=\u0026thinsp;0.39; I\u0026sup2; = 0%). The magnitude suggests a possible survival benefit, pointing to a comparable overall survival profile at 90 days. \u003cb\u003eSupplementary Fig.\u0026nbsp;5.\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec25\" class=\"Section2\"\u003e \u003ch2\u003e3.7. Certainty of Evidence:\u003c/h2\u003e \u003cp\u003eThe certainty of evidence for each outcome was evaluated using the GRADE approach. The certainty of evidence was rated as moderate for functional outcomes (mRS 0\u0026ndash;3, mRS 0\u0026ndash;2, mRS 0\u0026ndash;1), pre- and post-EVT perfusion, any intracranial hemorrhage, and 90-day mortality, primarily due to concerns related to imprecision. In contrast, the certainty of evidence was judged to be low for sICH and any parenchymal hematoma due to very serious imprecision driven by wide confidence intervals and low event rates. Overall, these findings indicate that confidence in the pooled estimates ranged from low to moderate across all assessed outcomes. The detailed summary of findings is provided in \u003cb\u003eSupplementary Table\u0026nbsp;4\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIschemic stroke of the posterior circulation accounts for a substantial proportion of strokes and is associated with high morbidity and mortality due to brainstem involvement and large vessel occlusion. Most thrombolytic trials have focused primarily on anterior circulation strokes, leaving uncertainty about the optimal intravenous thrombolytic strategy for posterior circulation stroke. In this meta-analysis, we specifically evaluated the comparative effectiveness of intravenous tenecteplase versus alteplase in patients with PCIS, thereby providing a focused synthesis of posterior circulation\u0026ndash;specific functional, perfusion, and safety outcomes.\u003c/p\u003e \u003cp\u003eIn this meta-analysis, we pooled evidence from five studies, including randomized and observational/post hoc posterior circulation data. Overall, tenecteplase was associated with a 29% higher likelihood of achieving an ambulatory functional outcome at 90 days (mRS 0\u0026ndash;3) compared with alteplase. For excellent (mRS 0\u0026ndash;1) and good (mRS 0\u0026ndash;2) functional outcomes, results favored tenecteplase; however, these differences did not reach statistical significance. Pre-EVT perfusion was more than twice as likely in the tenecteplase group, suggesting a potential advantage in early reperfusion. In contrast, post-EVT perfusion outcomes were comparable between groups, indicating similar final reperfusion success following intervention. Importantly, safety outcomes including sICH, any intracranial hemorrhage, parenchymal hematoma, and 90-day mortality\u0026mdash;were broadly similar between groups, with no meaningful increase in bleeding or mortality observed, although several estimates remain imprecise due to low event rates.\u003c/p\u003e \u003cp\u003eCompared with currently used thrombolytic strategies, tenecteplase offers several practical and pharmacologic advantages over alteplase in the treatment of acute ischemic stroke. Tenecteplase is a bioengineered variant of tissue plasminogen activator with amino acid substitutions that confer greater fibrin specificity, increased resistance to inhibition by plasminogen activator inhibitor‑1 (PAI‑1), and a significantly longer plasma half‑life than alteplase. These properties permit single‑bolus intravenous administration, rather than the bolus plus continuous infusion required for alteplase, and simplify preparation and dosing in emergency settings, potentially reducing workflow delays and medication errors (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). These mechanistic and workflow advantages may partly explain the observed association with higher pre-EVT perfusion and better ambulatory recovery in the present analysis. Many observational cohort studies have shown that tenecteplase is associated with significantly shorter door‑to‑needle and door‑to‑puncture times and a higher likelihood of meeting target acute stroke treatment benchmarks, as well as greater early neurological improvement at 24 hours, without increasing the risk of symptomatic or any intracranial hemorrhage compared with alteplase in routine clinical use (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). A real‑world analysis by Maxhuni et al., reported similar early clinical outcomes and safety profiles (including sICH and functional status at discharge) between tenecteplase and alteplase during the initial implementation of tenecteplase in a stroke center, supporting its effectiveness and tolerability outside of controlled trials (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Moreover, large multicenter registry data from the CERTAIN collaboration by Warach et al., demonstrated that tenecteplase use in routine clinical practice was associated with significantly lower odds of sICH than alteplase, reinforcing confidence in its safety profile in unselected AIS patients (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBeyond the functional and safety outcomes highlighted earlier, additional clinical evidence further supports the potential role of tenecteplase as a viable alternative to alteplase in AIS. Several larger meta‑analyses and systematic reviews have examined aggregated data from randomized trials and observational studies. However, these broader AIS findings should be interpreted cautiously when applied to posterior circulation stroke, because vertebrobasilar occlusion has distinct pathophysiologic and prognostic features and remains underrepresented in most thrombolysis datasets. A recent meta‑analysis by Shen et al., included over 7,508 patients across 16 randomized controlled trials found that tenecteplase was not inferior to alteplase for early thrombolytic therapy and even demonstrated advantages in early neurological improvement and vessel recanalization, without significant differences in safety outcomes such as sICH or mortality (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Moreover, a systematic review pooling nine RCTs reported comparable rates of functional independence and 90‑day mortality between tenecteplase and alteplase, while indicating trends toward greater early neurological recovery with tenecteplase, although statistical significance varied across outcomes (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Our findings are directionally consistent with these broader analyses, but add more specific insight into the posterior circulation subgroup. Taken together, these findings suggest that tenecteplase may offer an early reperfusion and ambulatory recovery advantage in PCIS, but the overall certainty of evidence remains limited and definitive superiority over alteplase cannot yet be concluded.\u003c/p\u003e \u003cp\u003e \u003cb\u003eLimitations\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eThis meta-analysis has several limitations that should be acknowledged. First, only five studies with a total of 997 patients were included, which limits the overall statistical power and may reduce the generalizability of the findings. Second, the pooled evidence was derived from a mixture of randomized and observational data, which may introduce methodological heterogeneity despite acceptable quality assessment results. Third, some of the included studies were not originally designed exclusively for PCIS, and or circulation data were extracted from subgroup analyses, which may weaken the strength of conclusions specific to this population. In addition, outcome definitions and reporting were not entirely uniform across studies, particularly for perfusion and recanalization-related endpoints, which may have affected comparability between studies. Differences in treatment workflows, including onset-to-needle time, EVT use, and institutional stroke protocols, may also have influenced outcomes. Furthermore, several safety endpoints such as sICH and parenchymal hematoma were based on low event rates, resulting in wide confidence intervals and limiting precision. Finally, the analysis relied on study-level rather than individual patient-level data, which restricted more detailed subgroup analyses according to stroke severity, occlusion site, thrombolytic dose, and timing of reperfusion therapy.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cdiv class=\"Heading\"\u003e\u003cb\u003e5. Conclusion\u003c/b\u003e:\u003c/div\u003e \u003cp\u003eIn patients with PCIS, intravenous tenecteplase was associated with improved ambulatory functional outcome (mRS 0\u0026ndash;3) and higher pre-EVT perfusion compared with alteplase, while other functional, perfusion, and safety outcomes were broadly similar between treatments. These findings suggest that tenecteplase may be an effective and safe alternative to alteplase in this subgroup. However, the evidence remains limited by small sample size, inclusion of mixed study designs, and low event rates for several safety endpoints. Larger posterior circulation\u0026ndash;specific prospective studies are needed to confirm whether the apparent early reperfusion and ambulatory outcome advantages of tenecteplase translate into consistent long-term clinical benefit.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eScientific Category:\u0026nbsp;\u003c/strong\u003eOriginal Research\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional review board approval and ethics committee clearance/Ethics approval:\u0026nbsp;\u003c/strong\u003eNot required\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient consent:\u0026nbsp;\u003c/strong\u003eNot required\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe data supporting the findings of this study were obtained from published studies. The data and material used were publicly available\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Conflicting Interests:\u0026nbsp;\u003c/strong\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e: Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNone received\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConception and design of the study:\u0026nbsp;\u003c/strong\u003eS.B.S, M.A, M.M\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnalysis and interpretation of data:\u0026nbsp;\u003c/strong\u003eM.H, M.J.R\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCollection or assembly of data:\u0026nbsp;\u003c/strong\u003eM.H, G.T.K\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDrafting or revising the article\u003c/strong\u003e: A.U, A.A.U\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinal approval of the version to be published:\u0026nbsp;\u003c/strong\u003eU.A, H.A\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSchneider AM, Neuhaus AA, Hadley G, Balami JS, Harston GW, DeLuca GC et al (2023) Posterior circulation ischaemic stroke diagnosis and management. 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Vol 2, Page 37. 2025;2(3):37. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ecm2030037\u003c/span\u003e\u003cspan address=\"10.3390/ecm2030037\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKobeissi H, Ghozy S, Turfe B, Bilgin C, Kadirvel R, Kallmes DF et al (2023) Tenecteplase vs. alteplase for treatment of acute ischemic stroke: A systematic review and meta-analysis of randomized trials. 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Neurol Ther 12(5):1553. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s40120-023-00530-4\u003c/span\u003e\u003cspan address=\"10.1007/s40120-023-00530-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003ePubMed PMID: 37552459\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh A, Singh MP, Gaikwad NR, Kannauje PK (2024) Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Systematic Review and Meta-analysis. Ann Neurosci 31(2):132\u0026ndash;142. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/09727531231193242\u003c/span\u003e\u003cspan address=\"10.1177/09727531231193242\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Tenecteplase, alteplase, Posterior circulation ischemic stroke, Stroke, Reperfusion","lastPublishedDoi":"10.21203/rs.3.rs-9389793/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9389793/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePosterior circulation ischemic stroke (PCIS) is associated with substantial morbidity and mortality, and the optimal intravenous thrombolytic strategy in this subgroup remains unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe searched databases for studies comparing intravenous tenecteplase with alteplase in adults with PCIS. Primary outcomes were 90-day functional outcomes (mRS 0\u0026ndash;1, mRS 0\u0026ndash;2, and mRS 0\u0026ndash;3). Secondary outcomes included perfusion, hemorrhagic complications, and mortality.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFive studies involving 997 patients were included. Tenecteplase was associated with significantly greater likelihood of ambulatory functional outcome at 90 days (mRS 0\u0026ndash;3) [RR 1.29, 95% CI 1.03\u0026ndash;1.60; p\u0026thinsp;=\u0026thinsp;0.02] and pre-EVT perfusion [RR 2.18, 95% CI 1.06\u0026ndash;4.46; p\u0026thinsp;=\u0026thinsp;0.03]. No significant differences were observed for excellent functional outcome (mRS 0\u0026ndash;1) [RR 1.19, 95% CI 0.91\u0026ndash;1.56; p\u0026thinsp;=\u0026thinsp;0.20], functional independence (mRS 0\u0026ndash;2) [RR 1.10, 95% CI 0.89\u0026ndash;1.37; p\u0026thinsp;=\u0026thinsp;0.39], post-EVT perfusion [RR 1.12, 95% CI 0.89\u0026ndash;1.40; p\u0026thinsp;=\u0026thinsp;0.34; I\u0026sup2; = 38%], sICH [RR 0.89, 95% CI 0.36\u0026ndash;2.22; p\u0026thinsp;=\u0026thinsp;0.81], any intracranial hemorrhage [RR 1.02, 95% CI 0.59\u0026ndash;1.78; p\u0026thinsp;=\u0026thinsp;0.94], parenchymal hematoma [RR 0.76, 95% CI 0.24\u0026ndash;2.38; p\u0026thinsp;=\u0026thinsp;0.64], or 90-day mortality [RR 0.88, 95% CI 0.66\u0026ndash;1.17; p\u0026thinsp;=\u0026thinsp;0.39].\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eTenecteplase may improve reperfusion and ambulatory recovery without increasing hemorrhagic complications, mortality compared with alteplase in PCIS, although larger PCIS-specific studies are needed.\u003c/p\u003e","manuscriptTitle":"Comparative Effectiveness of Intravenous Tenecteplase versus Alteplase in Posterior Circulation Ischemic Stroke: A Systematic Review and Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-14 15:11:13","doi":"10.21203/rs.3.rs-9389793/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c28896ea-0b97-4ccc-9631-a95e7442ee89","owner":[],"postedDate":"April 14th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":66141748,"name":"Clinical Pharmacology"}],"tags":[],"updatedAt":"2026-04-14T15:11:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-14 15:11:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9389793","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9389793","identity":"rs-9389793","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}