[Current and future aspects of intravenous thrombolysis for acute stroke]

Intravenous thrombolysis using alteplase was approved for clinical use for acute ischemic stroke treatment in Japan in 2005, on the basis of the results of a domestic clinical trial, Japan Alteplase Clinical Trial. This therapeutic strategy has become the standard strategy during the following 8 years. However, this therapy still has room for improvement. One of the important drawbacks of intravenous thrombolysis is the limited therapeutic time window. On the basis of the results of the European Cooperative Acute Stroke Study III and the pooled analysis, the current time window is within 4.5 h of stroke onset. The window may be extended to 6 h or longer, probably by appropriate determination of the eligibility of a patient for receiving therapy by using penumbral imaging techniques, such as diffusion-weighted imaging (DWI)/perfusion-weighted imaging mismatch and DWI/magnetic resonance imaging mismatch. Newer-generation recombinant tissue-type plasminogen activators, such as desmoteplase and tenecteplase, will also help extend the time window. Patients with wake-up and unclear-onset strokes are generally ineligible for thrombolysis; therefore, the optimal therapeutic strategy for such patients should be established. Another important drawback is acute stroke therapy paralleling or following intravenous thrombolysis. Mechanical recanalization by endovascular therapy, antithrombotic therapy, neuroprotective therapy (e.g., using intravenous free radical scavenger), and sonothrombolysis are promising candidates for combined use with intravenous thrombolysis.