Acute
ischaemic stroke is a leading cause of mortality and morbidity around the world. An arterial occlusive lesion is found in the majority of patients with acute
ischaemic stroke, and recanalisation has been shown to result in a better clinical outcome. The only widely approved recanalisation strategy is the use of intravenous
alteplase (recombinant
tissue-type plasminogen activator; tPA) within 3 hours of
stroke onset. However, this
therapy has limitations, and alternative or supplemental recanalisation strategies need to be considered in a large number of patients with acute
ischaemic stroke. One such promising strategy is intra-arterial thrombolysis. This article reviews the pharmacology of the various drugs used for intra-arterial thrombolysis in the setting of acute
ischaemic stroke and the results of the clinical trials that have studied their benefit. Three generations of
thrombolytic agents have been available for clinical use so far. The first-generation agents such as
streptokinase and
urokinase were the first to be studied in
acute stroke, and a number of positive case reports and series of their intra-arterial use have been reported from around the world. Second-generation products include
alteplase and
pro-urokinase. The clinical benefits of intra-arterial
pro-urokinase were recently proven in a randomised, placebo-controlled study. Third-generation agents, such as
reteplase,
lanoteplase and
tenecteplase, offer superior recanalisation rates with limited systemic adverse effects and might prove to be the agents of choice for intra-arterial
acute stroke thrombolysis in the future. The exact administration regimens as well as the identification of patient sub-populations most likely to benefit from intra-arterial thrombolysis are subjects of current investigations, and hopefully firmer guidelines will be established in the next few years, once the results of the clinical trials are available.