Clinical potential of intra-arterial thrombolytic therapy in patients with acute ischaemic stroke

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.