Key result
In computational simulations of acute ischemic stroke, tenecteplase showed similar thrombolysis efficacy to alteplase but with a lower risk of intracranial hemorrhage and better resistance to PAI-1.
Why the study?
Alteplase is the only FDA-approved drug for thrombolysis in acute ischemic stroke, but several other thrombolytic drugs are considered promising candidates to substitute it.
How do different intravenous thrombolytic agents compare in terms of efficacy and safety in a computational model of acute ischemic stroke?
How do different intravenous thrombolytic agents compare in terms of efficacy and safety in a computational model of acute ischemic stroke?
Computational modeling supports tenecteplase as a promising alternative to alteplase for acute ischemic stroke, offering similar efficacy with potentially lower ICH risk.
Simulation rankings of thrombolytics in AIS are hypothesis-generating; leaves open randomized trials before any substitution.
Alteplase is the only FDA-approved drug for thrombolysis in acute ischemic stroke (AIS). Meanwhile, several thrombolytic drugs are deemed to be promising candidates to substitute alteplase. This paper evaluates the efficacy and safety of urokinase, ateplase, tenecteplase, and reteplase for intravenous AIS therapy by computational simulations of the pharmacokinetics and pharmacodynamics combined with a local fibrinolysis model. The performances of the drugs are evaluated by comparing clot lysis time, plasminogen activator inhibitor (PAI) inhibition resistance, intracranial hemorrhage (ICH) risk, and activation time from drug administration to clot lysis. Our results reveal that urokinase has the quickest lysis completion but the highest ICH risk due to excess fibrinogen depletion in systemic plasma. While tenecteplase and alteplase have very similar thrombolysis efficacy, tenecteplase has a lower risk of ICH and better resistance to PAI-1. Among the four simulated drugs, reteplase has the slowest fibrinolysis rate, but fibrinogen concentration in systemic plasma is unaffected during thrombolysis.
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Yang et al. (2023) studied Acute ischemic stroke. Urokinase, alteplase, tenecteplase, and reteplase vs. Each other was evaluated on Clot lysis time, plasminogen activator inhibitor (PAI) inhibition resistance, intracranial hemorrhage (ICH) risk, and activation time. In computational simulations of acute ischemic stroke, tenecteplase showed similar thrombolysis efficacy to alteplase but with a lower risk of intracranial hemorrhage and better resistance to PAI-1.
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