Systemic reperfusion therapy in acute ischemic stroke

Introduction: 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.

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

Results: 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.

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