Q&A

Thrombolytic therapy for acute ischemic stroke: risks vs benefits

J Fam Pract. 2003 October;52(10):747-769
By
Erik J. Lindbloom, MD, MSPH
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  • BACKGROUND: The research on the use of rtPA for victims of acute ischemic stroke has shown a mixed effect. Initially optimistic results demonstrated in highly controlled clinical settings have not been replicated in studies of more typical use. This meta-analysis reviewed and incorporated the accumulated new evidence evaluating the outcomes of rtPA use.
  • POPULATION STUDIED: The authors included randomized controlled trials of thrombolytic agents administered within 6 hours of the onset of image-confirmed nonhemorrhagic stroke. Although this article focuses on rtPA, studies of other thrombolytics (such as streptokinase and prourokinase) were also reviewed. Published and unpublished studies were eligible, but no unpublished studies were found. Publications not in English were translated and included.
  • STUDY DESIGN AND VALIDITY: As part of the Cochrane Database of Systematic Reviews, this was a thorough meta-analysis with clear search criteria as outlined in the Cochrane Library. The authors considered 1992 to be the first year with a modern thrombolytic trial in the setting of acute hemorrhagic stroke, and they performed a separate analysis in each year with new data.
  • OUTCOMES MEASURED: The primary outcomes were death or dependence on others for performance of activities of daily living (dependency) within 3 to 6 months of treatment, and symptomatic intracranial hemorrhage within 10 days of treatment. Dependency was measured with 1 of 2 previously validated instruments, the modified Rankin Scale and the Barthel Index. Symptomatic intracranial hemorrhage included any neurological deterioration or death temporally associated with a new intracranial hemorrhage seen on computed tomography scan or autopsy.
  • RESULTS: A total of 6 rtPA trials enrolling 2830 patients were included in this analysis. The combined endpoint of death or dependency favored rtPA (odds ratio [OR]=0.80; 95% confidence interval [CI], 0.69–0.93). In terms of absolute risk reduction, 55 fewer patients out of 1000 treated would be dead or dependent within 3 to 6 months of treatment (number needed to treat [NNT]=19). However, it appears likely that this benefit was due only to the reduction in longterm disability.
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PRACTICE RECOMMENDATIONS

The evidence is not strong enough to recommend routine use of recombinant tissue plasminogen activator (rtPA) in the setting of acute ischemic stroke.

Although independence in activities of daily living 3 to 6 months later is better in those who receive rtPA, acute adverse events (including fatal intracranial hemorrhage) also significantly increase. Given the potentially fatal risks and heterogeneity of results among trials, thrombolytic therapy in the setting of acute ischemic stroke needs more investigation. In the future, we may be able to define a more specific group of patients for whom the potential benefits clearly outweigh the risks.

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