Thrombolytic therapy for acute ischemic stroke was established in 1995, when the National Institutes of Neurological Disorders and Stroke recombinant tissue–type Plasminogen Activator Stroke Study (NINDS rt–PA stroke study) group revealed the efficacy of intravenous alteplase infusion at 0.9mg/kg. The drug, alteplase, was introduced to Japan in 2005 after Japan Alteplase Clinical Trial (J–ACT) showed identical efficacy and safety to NINDS study using a reduced dose of 0.6mg/kg. The time allowance for the use of the drug was extended from 3 hours to 4.5 hours in 2012 in Japan. This therapy is still being investigating in several ways : 1) Optimal dosing, 0.6mg/kg vs. 0.9mg/kg, was investigated on the Enhanced Control of Hypertension and Thrombolysis Stroke Study, 2) extending time window over 4.5 hours using advanced brain imaging, 3) Introduction of mobile stroke unit that enables field administration, 4) Developing new–generation thrombolytic drugs that have more fibrin specificity, better plasminogen activator inhibitor resistance and longer half–life than alteplase.
Streptokinase, alteplase, duteplase, desmoteplase, and tenecteplase are the previously or currently tested drugs as for the use of acute thrombolytic therapy. Among them, alteplase is the only drug approved to use in clinical settings. Other drugs except for tenecteplase were failed to proceed to clinical application. Tenecteplase is currently the only drug that has possibility to replace alteplase in the future. Several phase III studies comparing tenecteplase with alteplase are currently ongoing. In Japan, however, tenecteplase is officially not available currently, even for acute myocardial infarction. The most advanced study, Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation (TASTE), is targeting more than 1,000 stroke patients who have targeted mismatch on advanced brain imaging within 4.5 hours. Should tenecteplase proved better efficacy and safety over alteplase, international standard drug will be replaced to tenecteplase.