Title:Thrombolytic Agents for Acute Ischaemic Stroke Treatment: The Past, Present and Future
Volume: 12
Issue: 2
Author(s): Joyce S. Balami, Ruoli Chen, Brad A. Sutherland and Alastair M. Buchan
Affiliation:
Keywords:
Ischaemic stroke, thrombolytics, plasminogen activators, direct fibrinolytics, thrombolysis.
Abstract: Despite advances in the diagnosis and treatment of acute ischaemic stroke in the past two decades, stroke has
remained the third cause of mortality and the single leading cause of disability worldwide. The immediate goal of acute
ischaemic stroke therapy is to salvage the ischaemic penumbra through recanalisation of the occluded cerebral blood
vessel. This is currently achieved through thrombolytics, which are pharmacological agents that can break up a clot
blocking the flow of blood. To date, the only approved thrombolytic for treatment of acute ischaemic stroke is
recombinant tissue plasminogen activator (alteplase, rt-PA), however, alteplase is substantially underused because of
concerns regarding adverse bleeding risk. This limitation has fuelled the search for other thrombolytic agents, which
display greater fibrin dependence and selectivity, but lack detrimental effects within the central nervous system.
Development of alternative fibrinolytic agents that might be easier and safer to administer could lead to wider acceptance
and use of thrombolytic therapy for stroke. Although other thrombolytic agents (e.g. streptokinase) have failed to show
benefit over alteplase, there is still on-going research in search of alternative agents with higher target specificity and
better safety profile. The potential thrombolytic agents with trials in progress include desmoteplase, tenecteplase,
reteplase, plasmin and microplasmin. This review summarises current therapies with thrombolytics (e.g. alteplase and
urokinase), their limitations and side effects, and also discusses ongoing clinical studies with the various potential
emerging thrombolytic agents.
