[Novel Drugs and Therapeutic Strategies for Acute Ischemic Stroke:Focus on Tenecteplase].

Abstract

Intravenous thrombolysis remains a cornerstone of acute ischemic stroke treatment, but alteplase has a short half-life and requires complex administration. Tenecteplase (TNK) , a genetically modified variant of alteplase, is regarded as a next-generation recombinant tissue-type plasminogen activator. TNK has greater fibrin specificity, a longer half-life, and greater resistance to plasminogen activator inhibitor-1, enabling single-bolus administration. Several randomized trials have supported its efficacy and safety, and its clinical use has expanded internationally. However, in Japan, alteplase at 0.6 mg/kg is the approved standard dose, and direct evidence comparing this regimen with TNK has been lacking. The investigator-initiated T-FLAVOR trial directly compared TNK 0.25 mg/kg with alteplase 0.6 mg/kg in patients with large-vessel occlusion scheduled for mechanical thrombectomy. In the T-FLAVOR trial, TNK achieved a higher rate of reperfusion on initial angiography, with comparable safety outcomes. These findings provide important evidence supporting the potential regulatory approval and clinical implementation of TNK in Japan. Other emerging therapies, including thrombolytic agents (JX10), neuroprotective agents (nerinetide), anti-edema drugs (glibenclamide), and antithrombotic agents such as factor XIa inhibitors (milvexian and asundexian), may further broaden treatment options across the acute treatment and secondary prevention phases of ischemic stroke.