Systemic Recombinant Tissue Plasminogen Activator for Treatment of Acute Ischemic Cerebral Stroke; A Systematic Review

Abstract

Stroke is ranked as the second leading cause of death worldwide with an annual mortality rate of about 5.5 million. Not only does the burden of stroke lie in the high mortality but the high morbidity also results in up to 50% of survivors being chronically disabled. Generally, Stroke can be classified in to two major categories, namely, ischemic stroke and hemorrhagic stroke. There are several sub classification schemes for ischemic stroke and the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria is the most widely used. Based on the TOAST criteria, ischemic stroke can be grouped into five main pathological or etiological types. Since the 1990s, intravenous (IV) tissue plasminogen activator (IV tPA) has been the only evidence-based therapeutic option for improving outcomes for patients with AIS. Subsequently, intra-arterial thrombolysis (IAT) was tested in the Prolyse in Acute Cerebral Thromboembolism II (PROACT II) study, which found potential safety and efficacy of IAT for middle cerebral artery (MCA) occlusions treated within 6 hours. Subsequently, the Interventional Management of Stroke (IMS) trial investigated the feasibility and safety of combined IV and intra-arterial therapy in AIS. Recombinant tissue plasminogen activators (rtPAs) produced using genetic engineering techniques exhibit longer half-lives than native tPA, allowing convenient bolus dosing, enhanced fibrin specificity, and higher resistance to inactivation by PAI‐1 Although, intravenous rt-PA for AIS showed a significant increase in survival free of disability, there is still a discrepancy within the published literature regarding the role of rt-PA in the setting AIS. Thus,