Recombinant tissue plasminogen activator (rtPA) for stroke - The perspective at 8 years

Objective: To review the 8-year experience with recombinant tissue plasminogen activator (rtPA) for stroke, with commentary on ramifications for the approach to stroke treatment, directions in stroke research, and sociological aspects of stroke as a disease of concern in our society. Background: Approved in 1996, rtPA remains the only drug indicated for the treatment of ischemic stroke. Stroke treatment and research have evolved rapidly in response to opportunities and discoveries related to the advent of rtPA. The presence of rtPA has engendered an increased level of awareness about all aspects of stroke. Methodology: Literature review was performed, focusing on topics that in the author's view are of greatest relevance to the use of rtPA in clinical practice and to the directions in which the presence of rtPA is moving the field of stroke treatment, research, and politics. Results: Challenges have been raised, and met, regarding the validity of the data upon which the approval for rtPA was based. Limitations in the use of rtPA include the brief time available for treatment, the need for rapid imaging and blood-pressure control, and the fact that large-artery occlusions respond poorly. The major risk of treatment is brain hemorrhage, and although predictors of hemorrhage are known, their presence does not constitute an absolute contraindication to treatment. A virtual subindustry has evolved to enhance the benefit and applicability of rtPA through refined imaging technology and the use of rtPA intra-aterially, as well as in combination with other agents and devices. Sociopolitically, rtPA has elevated the level of awareness of stroke and provided impetus for the stroke center movement and federal legislation to stop stroke. Conclusion: The development of rtPA has been the most effective advance in the field of stroke. It has generated healthy debate regarding the design, performance, and interpretation of stroke trials, including cost-benefit considerations. rtPA has stimulated research in a multitude of areas, enhanced our understanding of stroke pathophysiology, and defined important limits and risks for urgent intervention. rtPA is the cornerstone of the stroke center movement, as well as legislation in behalf of stroke at the congressional level.