Comparative Efficacy and Safety of Tissue Plasminogen Activators (tPAs) in Acute Ischemic Stroke: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Sufyan Shahid1, Humza Saeed2, Minahil Iqbal3, Aqeeb Ur Rehman4, Muhammad Aemaz Ur Rehman4, Japleen Kaur5
1Khawaja Muhammad Safdar Medical College, 2Rawalpindi Medical University, Rawalpindi, Pakistan, 3Allama Iqbal Medical College, Lahore, Pakistan, 4University of Alabama at Birmingham, 5Department of Neurosciences, University of California, San Diego
Objective:
We conducted a systematic review and network meta-analysis to assess the efficacy and safety of various tPAs in patients with acute ischemic stroke.
Background:
Intravenous alteplase is the standard treatment for acute ischemic stroke. However, recent trials comparing different tissue plasminogen activators (tPAs) to alteplase have yielded conflicting results.
Design/Methods:
A systematic literature search was conducted using PubMed, Embase, Web of Science, and Cochrane Library until July 12, 2024. We included randomized controlled trials comparing tenecteplase or reteplase to alteplase in patients with acute ischemic stroke. We performed a frequentist network meta-analysis using risk ratio and 95% CI for each comparison. P-scores provided a ranking of treatments. Statistical analyses were performed using R Software 4.2.3 and MetaInsight.
Results:
15 randomized controlled trials with a total of 7,817 patients (40% female) were included. Reteplase 18+18 mg (RR 1.13; 95% CI 1.06-1.20) and tenecteplase 0.25 mg (RR 1.09; 95% CI 1.03-1.15) demonstrated a significant improvement in excellent functional outcome compared to alteplase. Additionally, reteplase 18+18 mg was also significant for functional independence compared to alteplase (RR 1.07; 95% CI 1.02-1.12). All three treatments had similar 90-day mortality rates. However, tenecteplase 0.1 mg was associated with a higher risk of symptomatic intracerebral hemorrhage (sICH) compared to alteplase (RR 1.13; 95%CI 1.06-1.20).
Conclusions:
Reteplase 18+18 mg and tenecteplase 0.25 mg showed higher efficacy and comparable safety profiles to alteplase in this network meta-analysis. However, future trials are needed to consider these agents as a potential alternative to alteplase.
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