Comparative efficacy and safety of tenecteplase and alteplase in acute ischemic stroke: A pairwise and network meta-analysis of randomized controlled trials

Rehman, Aqeeb Ur; Mohsin, Aleenah; Cheema, Huzaifa Ahmad; Zahid, Afra; Rehman, Muhammad Ebaad Ur; Ameer, Muhammad Zain; Ayyan, Muhammad; Ehsan, Muhammad; Shahid, Abia; Rehman, Muhammad Aemaz Ur; Shah, Jaffer; Khawaja, Ayaz

doi:10.1016/j.jns.2022.120537

Cited by 13 publications

(7 citation statements)

References 28 publications

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“…Notably, Plat has been extensively studied for its therapeutic potential in treating thrombotic disorders like ischemic stroke and myocardial infraction. [84][85][86][87][88] Therefore, further research is required to clarify the exact role of Plat in osteoblast differentiation and bone formation and its potential as a therapeutic target for osteoporosis and other bone-related disorders.…”

Section: Discussionmentioning

confidence: 99%

“…These findings underscore the complex and context‐dependent roles of Plat and PAI‐1 in bone physiology and highlight the importance of investigating their regulation and interactions in osteoblast differentiation. Notably, Plat has been extensively studied for its therapeutic potential in treating thrombotic disorders like ischemic stroke and myocardial infraction 84–88 . Therefore, further research is required to clarify the exact role of Plat in osteoblast differentiation and bone formation and its potential as a therapeutic target for osteoporosis and other bone‐related disorders.…”

Section: Discussionmentioning

confidence: 99%

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Mechanical induction of osteoanabolic Wnt1 promotes osteoblast differentiation via Plat

Ahmad,

Haffner‐Luntzer,

Schoppa

et al. 2024

The FASEB Journal

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Physical activity‐induced mechanical stimuli play a crucial role in preserving bone mass and structure by promoting bone formation. While the Wnt pathway is pivotal for mediating the osteoblast response to loading, the exact mechanisms are not fully understood. Here, we found that mechanical stimulation induces osteoblastic Wnt1 expression, resulting in an upregulation of key osteogenic marker genes, including Runx2 and Sp7, while Wnt1 knockdown using siRNA prevented these effects. RNAseq analysis identified Plat as a major target through which Wnt1 exerts its osteogenic influence. This was corroborated by Plat depletion using siRNA, confirming its positive role in osteogenic differentiation. Moreover, we demonstrated that mechanical stimulation enhances Plat expression, which, in turn leads to increased expression of osteogenic markers like Runx2 and Sp7. Notably, Plat depletion by siRNA prevented this effect. We have established that Wnt1 regulates Plat expression by activating β‐Catenin. Silencing Wnt1 impairs mechanically induced β‐Catenin activation, subsequently reducing Plat expression. Furthermore, our findings showed that Wnt1 is essential for osteoblasts to respond to mechanical stimulation and induce Runx2 and Sp7 expression, in part through the Wnt1/β‐Catenin/Plat signaling pathway. Additionally, we observed significantly reduced Wnt1 and Plat expression in bones from ovariectomy (OVX)‐induced and age‐related osteoporotic mouse models compared with non‐OVX and young mice, respectively. Overall, our data suggested that Wnt1 and Plat play significant roles in mechanically induced osteogenesis. Their decreased expression in bones from OVX and aged mice highlights their potential involvement in post‐menopausal and age‐related osteoporosis, respectively.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mechanical induction of osteoanabolic Wnt1 promotes osteoblast differentiation via Plat

Ahmad,

Haffner‐Luntzer,

Schoppa

et al. 2024

The FASEB Journal

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Section: Discussionmentioning

confidence: 99%

“…Several systematic reviews and meta-analyses have compared the effectiveness and safety of TNK and alteplase for treating AIS with superior and non-inferiority designs. [33][34][35][36][37][38][39][40][41][42][43][44][45] Overall, the studies suggested that TNK may be more effective than Alteplase in improving early neurological function and higher recanalization rates; there have been no significant differences between the two drugs regarding functional outcomes, disability-free three-month outcomes, or mortality. The optimal dose of TNK appears to be 0.25 mg/kg, which has been shown to have the greatest odds of achieving early neurological improvement and an excellent functional outcome at three months, with reduced odds of ICH.…”

Section: Studymentioning

confidence: 99%

“…The optimal dose of TNK appears to be 0.25 mg/kg, which has been shown to have the greatest odds of achieving early neurological improvement and an excellent functional outcome at three months, with reduced odds of ICH. [33][34][35][36][37][38][39][40][41][42][43][44][45] A recently published randomized controlled noninferiority trial involving 1,430 participants conducted in China evaluated the efficacy and safety of TNK compared to Alteplase in adults with an AIS who were not eligible for endovascular thrombectomy. The results showed that the TNK and Alteplase were comparable in efficacy (mRS score of 0-1 at 90 days) and safety (mortality and ICH).…”

Section: Studymentioning

confidence: 99%

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Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Systematic Review and Meta-analysis

Singh,

Gaikwad

et al. 2023

Annals of Neurosciences

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Background A number of clinical trials have compared tenecteplase (TNK) and alteplase for the management of acute ischemic stroke (AIS) and the results are inconsistent. Purpose Present systematic review and meta-analysis is undertaken to analyse the efficacy and safety of TNK in AIS compared to alteplase. Summary A thorough literature search was performed through the databases Embase, Cochrane Library, PubMed, and clinicaltrials.gov, for a period from inception to September 2022, with the keywords i.e., “tenecteplase” and “alteplase” and “acute ischemic stroke.” Clinical trials published in English that compared the efficacy and safety of TNK to alteplase in AIS were included. The major outcomes of this meta-analysis were proportion of patients free from disability and functional independence at 90 days, early neurological improvement at 24 hours, all-cause mortality at 90 days, patients with intra cranial hemorrhage (ICH), and patients with severe disability at 90 days. A total of nine studies with 3,573 patients were included in the analysis. The proportion of patients with freedom from disability was comparable in both groups (relative risk [RR] = 1.04, 95 per cent CI = 0.92–1.17; p = .53). Similarly, proportion of patients with functional independence was comparable (RR = 1.12, 95 per cent CI = 0.96–1.31; p = .14). TNK group had a higher rate of early neurological recovery (RR = 1.56, 95 per cent CI = 0.96–2.54; p = .07). All-cause mortality at 90 days was comparable in both groups (RR = 0.97; 95 per cent CI = 0.72–1.29; p = .82). The proportion of patients with ICH was higher in TNK group (RR = 1.14, 95 per cent CI = 0.77–1.68; p = .52). The proportion of patients with severe disability was less in TNK group (RR =0.84, 95 per cent CI = 0.53–1.32; p = .44). Key Message TNK was similar to alteplase in terms of efficacy and safety. The patients in TNK group showed early neurological improvement but were simultaneously at higher risk of ICH. The TNK can be an alternative to alteplase if the benefits outweigh the risks.

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Common Neurologic Issues

Christie,

Sharrief

2024

Geriatric Home-Based Medical Care

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Comparative efficacy and safety of tenecteplase and alteplase in acute ischemic stroke: A pairwise and network meta-analysis of randomized controlled trials

Cited by 13 publications

References 28 publications

Mechanical induction of osteoanabolic Wnt1 promotes osteoblast differentiation via Plat

Mechanical induction of osteoanabolic Wnt1 promotes osteoblast differentiation via Plat

Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Systematic Review and Meta-analysis

Common Neurologic Issues

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