Systemic reperfusion therapy in acute ischemic stroke

Experimental and clinical studies indicate that early reperfusion of occluded brain-supplying arteries reduces the size of injury and improves outcome. Recombinant tissue plasminogen activator (t-PA) is the only drug approved for systemic reperfusion in acute ischemic stroke. However, the use of intravenous t-PA is currently limited by its narrow therapeutic window.

We reviewed the approaches to extending systemic reperfusion in cerebral ischemia currently under investigation in human clinical studies.

Strategies to expand the systemic reperfusion include: a better use of conventional t-PA; to extend the intravenous rt-PA window to 270 min; new fibrinolytic agents (tenecteplase, microplasmin, desmoteplase, V10153); combination of lytics and antithrombotics (t-PA + tirofibran, t-PA + abciximab, reteplase + abciximab, t-PA + eptifibatide and t-PA + eptifibatide + aspirin + tinzaparin); combination of lytics and neuroprotectans; externally applied ultrasound to enhance enzymatic fibrinolysis, and improving patient selection with multimodal imaging.

There is considerable opportunity to explore safe strategies to expand systemic reperfusion therapy which could further benefit stroke outcome.