Recombinant Tissue-Type Plasminogen Activator (Alteplase) in the Management of Acute Ischemic Stroke: A Review of its Pharmacological Properties, Efficacy, Safety and Pharmacoeconomic Aspects

Naveed      Akhtar; Dirk      Deleu; Sadaat      Kamran

Abstract

Ischemic stroke ranks as one of the major leading cause of death and the most common cause of acquired neurological disability in adults. The treatment of acute ischemic stroke remains one of the most challenging areas in medicine today. Timely recognition and treatment is imperative to reduce its morbidity and mortality. So far, intravenous recombinant tissue-type plasminogen activator (rt-PA or alteplase) is the only approved thrombolytic by the European Agency for the Evaluation of Medicinal Products (EMEA) and Food and Drug Administration (FDA) for treating acute ischemic stroke within three hours of onset of symptoms. Though encouraging, the data for a larger therapeutic window between 3 and 6 hours remains controversial. Other treatment strategies (using intra-arterial alteplase combined intravenous/intra-arterial alteplase, other thrombolytic agents, mechanical disruption of clot and ultrasonic augmentation of thrombolysis) although still under investigation, have shown beneficial in selected conditions. Still thrombolytic therapy has not been widely adopted and practiced. This limited implementation may be because of many factors including clinical and time criteria, and most of all lack of public and professional education for understanding stroke as acute emergency. The objective of this paper is to provide an updated overview of the use of alteplase in acute ischemic stroke in all its aspects: mechanism of action, pharmacokinetics, drug interactions, efficacy and tolerability via different routes of administration in the anterior and posterior circulation, and last but not least the pharmacoeconomic issues. The rationale for thrombolytic therapy and its limits will be addressed. Educating the general public, training emergency caregivers and allied health professionals, and addressing long-term cost savings to health institutions will make stroke management optimized and widely available.

Keywords: Ischemic stroke, Alteplase, Intravenous, Intraarterial, Efficacy, Safety, Pharmacoeconomics

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