Extending reperfusion therapy for acute ischemic stroke: emerging pharmacological, mechanical, and imaging strategies

Reperfusion is the most beneficial of all therapeutic strategies for acute ischemic stroke. However, the standard cerebral reperfusion treatment of the first decade of the reperfusion era, noncontrast computed tomography (CT)-guided, < or =3 hours, intravenous tissue plasminogen activator, has many limitations. This review surveys emerging strategies that have the potential to extend cerebral reperfusion therapy to larger numbers of patients.

Innovative intravenous pharmacological reperfusion strategies include novel fibrinolytic agents (tenecteplase, reteplase, desmetolplase, plasmin, and microplasmin), glycoprotein (GP) IIb/IIIa antagonists with platelet disaggregating effects (abciximab and tirofiban), combination therapies to improve efficacy of clot lysis (fibrinolytics and GP IIb/IIIa agents, and fibrinolytics and direct thrombin inhibitors), increase the time window for clot lysis (fibrinolytics and neuroprotectants), and reduce the frequency of hemorrhagic complications (fibrinolytics and vasoprotectants), and externally applied ultrasound to enhance enzymatic fibrinolysis. Promising intra-arterial pharmacological reperfusion approaches include novel fibrinolytic agents, combined intravenous and intra-arterial fibrinolysis, and combined fibrinolytics and GP IIb/IIIa agents. Emerging endovascular mechanical reperfusion strategies include intra-arterial thrombectomy (clot retrieval devices and suction thrombectomy devices), mechanical disruption (micro-guidewire passage, laser photoacoustic emulsification, and primary intracranial angioplasty), and augmented fibrinolysis by endovascular ultrasound. Multimodal imaging, with magnetic resonance (MR) or CT, can rapidly assess infarct core, penumbra, site of vessel occlusion, and tissue hemorrhagic propensity, enabling improved selection of patients for reperfusion therapy beyond any arbitrary fixed time window.

Therapeutic reperfusion is emerging as a treatment strategy of remarkable power and scope for rescuing patients experiencing acute brain ischemia, applicable within and beyond the 3-hour time window.