Should We Switch to Tenecteplase for all Ischaemic Strokes? Evidence and Logistics

Int J Stroke. 2024 Nov 30:17474930241307098. doi: 10.1177/17474930241307098. Online ahead of print.

Abstract

Recent clinical trials provide robust evidence of non-inferiority of tenecteplase 0.25mg/kg over alteplase 0.9mg/kg in acute ischaemic stroke treated within 4.5h of time last known well. Aggregate data meta-analysis suggests likely superiority of tenecteplase with respect to excellent (modified Rankin Scale 0 or 1) outcomes at 90 days. Less complex single intravenous bolus administration of tenecteplase brings significant logistical benefits compared to alteplase. Real-world implementation data demonstrate reduced door-to-needle and door-to-puncture times, and potentially improved clinical outcomes. Avoiding the need for infusion pumps and monitoring reduces resource requirements and facilitates inter-hospital transfer. Guidelines favour tenecteplase over alteplase due to its logistical advantages. Transitioning services to tenecteplase requires consideration of education and training for all relevant staff (medical, nursing, pharmacy) and should address physician concerns. Use of stroke-specific tenecteplase 25mg dose vials is strongly preferable to minimise the chance of dosing errors that might arise from use of cardiac-dose tenecteplase. Some off-label uses of alteplase are supported by positive randomised controlled trial data (wake-up and unknown onset stroke, and imaging-supported late window use 4.5-9h after onset) while equivalent data for tenecteplase are less conclusive. Trial data comparing tenecteplase to control give relevant safety data for both wake-up / unknown onset stroke and for late time windows, and some efficacy data favour tenecteplase in a late time window. Given the weight of evidence for biologically similar efficacy and safety of tenecteplase 0.25mg/kg, and potential for dosing errors, retention of alteplase for off-label indications should not be recommended. Some off-label uses of alteplase are supported by positive randomised controlled trial data (wake-up and unknown onset stroke, and imaging-supported late window use 4.5-9h after onset) while equivalent data for tenecteplase are less conclusive. Trial data comparing tenecteplase to control give relevant safety data for both wake-up / unknown onset stroke and for late time windows, and some efficacy data favour tenecteplase in a late time window. Given the weight of evidence for biologically similar efficacy and safety of tenecteplase 0.25mg/kg, and potential for dosing errors, retention of alteplase for off-label indications should not be recommended.

Keywords: Acute; Acute stroke therapy; Tenecteplase; Thrombolysis; rtPA; tPA.