IV THROMBOLYSIS After the seminal National Institute of Neurological Disorders and Stroke trial published in 1995, 1 IV thrombolysis with recombinant tissue plasminogen activator (rtPA), specifically alteplase, became the standard in acute ischemic stroke treatment. The time window to treatment was initially confined to 3 hours from symptom onset and later expanded to 4.5 hours from last known well. 2 The biggest risk of IV thrombolysis is symptomatic hemorrhagic transformation and is estimated to occur in 2% to 7% of treated patients, which varies based on the patient population studied as well as the definition of hemorrhagic transformation used. 3 The benefit, as well as the risk, of IV thrombolysis is time-dependent, with earlier administration from symptom onset yielding improved outcomes. 4-6 The recommended dose of IV alteplase is 0.9 mg/kg (maximum dose, 90 mg), given as 10% of the total dose as a bolus followed by infusion of the remaining 90% over 60 minutes. 1,6 As a general rule, patients with a bleeding diathesis should likely be excluded from treatment, and a more detailed list of exclusion and inclusion criteria can be found in TABLE 4-1. 6-8 Tenecteplase, a third-generation thrombolytic agent, has become an attractive alternative to alteplase. Biologically, tenecteplase has a higher fibrin specificity and longer half-life than alteplase. Additionally, tenecteplase can be administered as a one-time bolus, making it a more practical option. Compiling data from early studies examining dosing, a 0.25-mg/kg one-time bolus of tenecteplase is an acceptable dose when balancing efficacy and risk of hemorrhage. 9-13 Importantly, a 2024 systematic review and meta-analysis demonstrated a higher likelihood for excellent functional outcome and reduced disability at 90 days with tenecteplase (0.25 mg/kg) when compared with alteplase (0.9 mg/kg). 14 Given these data, over the past few years, there has been a trend in stroke centers switching from using alteplase to tenecteplase. In 2025, tenecteplase 0.25 mg/kg, with a maximum dose of 25 mg, was FDA approved for the treatment of acute ischemic stroke (TABLE 4-1). Reteplase, another third-generation thrombolytic agent, was recently shown to have better 90-day clinical outcomes than alteplase in patients with acute ischemic stroke treated within 4.5 hours of symptom onset. 15 There was, however, an increased incidence of hemorrhage with reteplase compared with alteplase. Because of limited generalizability (eg, the study included a predominantly Asian population and excluded endovascular therapy candidates and patients older than 80 years), further studies replicating these findings in a broader population are needed. PPT SLIDES PRESENTATION
IV THROMBOLYSIS After the seminal National Institute of Neurological Disorders and Stroke trial published in 1995, 1 IV thrombolysis with recombinant tissue plasminogen activator (rtPA), specifically alteplase, became the standard in acute ischemic stroke treatment. The time window to treatment was initially confined to 3 hours from symptom onset and later expanded to 4.5 hours from last known well. 2 The biggest risk of IV thrombolysis is symptomatic hemorrhagic transformation and is estimated to occur in 2% to 7% of treated patients, which varies based on the patient population studied as well as the definition of hemorrhagic transformation used. 3 The benefit, as well as the risk, of IV thrombolysis is time-dependent, with earlier administration from symptom onset yielding improved outcomes. 4-6 The recommended dose of IV alteplase is 0.9 mg/kg (maximum dose, 90 mg), given as 10% of the total dose as a bolus followed by infusion of the remaining 90% over 60 minutes. 1,6 As a general rule, patients with a bleeding diathesis should likely be excluded from treatment, and a more detailed list of exclusion and inclusion criteria can be found in TABLE 4-1. 6-8 Tenecteplase, a third-generation thrombolytic agent, has become an attractive alternative to alteplase. Biologically, tenecteplase has a higher fibrin specificity and longer half-life than alteplase. Additionally, tenecteplase can be administered as a one-time bolus, making it a more practical option. Compiling data from early studies examining dosing, a 0.25-mg/kg one-time bolus of tenecteplase is an acceptable dose when balancing efficacy and risk of hemorrhage. 9-13 Importantly, a 2024 systematic review and meta-analysis demonstrated a higher likelihood for excellent functional outcome and reduced disability at 90 days with tenecteplase (0.25 mg/kg) when compared with alteplase (0.9 mg/kg). 14 Given these data, over the past few years, there has been a trend in stroke centers switching from using alteplase to tenecteplase. In 2025, tenecteplase 0.25 mg/kg, with a maximum dose of 25 mg, was FDA approved for the treatment of acute ischemic stroke (TABLE 4-1). Reteplase, another third-generation thrombolytic agent, was recently shown to have better 90-day clinical outcomes than alteplase in patients with acute ischemic stroke treated within 4.5 hours of symptom onset. 15 There was, however, an increased incidence of hemorrhage with reteplase compared with alteplase. Because of limited generalizability (eg, the study included a predominantly Asian population and excluded endovascular therapy candidates and patients older than 80 years), further studies replicating these findings in a broader population are needed. PPT SLIDES PRESENTATION
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IV thrombolysis is a critical standard of care for stroke management, established by NINDS in 1995 with alteplase as the primary agent. The treatment window spans from 3 to 4.5 hours, emphasizing that earlier intervention enhances patient outcomes. Administering thrombolytic therapy involves a dosage of 0.9 mg/kg of alteplase, with careful screening for bleeding risks. Emerging therapies like tenecteplase and reteplase are gaining attention, with tenecteplase showing promising functional...