TDNet Discover

Background: Alteplase/tPA is the gold standard of care in treating a confirmed acute ischemic stroke when onset is within 4.5-hours. However, its benefits have not been established among these patients when the stroke onset was >4.5 hours or with unknown onset. Purpose: The purpose of this study is to establish whether there is benefit using alteplase/tPA past the 4.5-hour time frame over the general standard of care in patients with confirmed acute ischemic stroke. Methods: We searched the Medline, PubMed, JSTOR, Google Scholar, CINAHL and Cochrane databases for randomized controlled trials that compared the use of alteplase within the accepted window, outside the accepted window and placebo groups to evaluate the benefits and risks of utilizing alteplase within these groups. The data of interest involved the favorable functional outcome as measured by the Modified Rankin Scale (mRS) score of 0-1 at the 90 day mark, the score of 0-2 for functional independence at 90 days, and risks of symptomatic intracerebral hemorrhage (sICH) and mortality at the 90 day mark. Bias was assessed using a quality assessment tool from NIH. Results: Six trials involving a total of 5,774 patients were used with minimal bias. Patients in the alteplase group were more likely to achieve favorable functional outcomes (45.8% vs 36.7%) and functional independence (63.8% vs 55.7%) at the 90 day marks, but had a higher risk of sICH (3.0% vs. 0.5%;OR 5.28, 95% CI 1.35– 20.68) at 90 days than those that were in the placebo control groups. No significant difference for mortality at the 90 day mark was found between the two groups (adjusted odds ratio, 3.38;95% CI, 0.92 to 12.52;p = 0.07). Conclusion: The use of alteplase therapy in the extended time window may improve the functional outcome of patients at the 90 day mark despite the possible increased risk of sICH. Before guidelines can be adjusted, further research should be completed on the benefits and risks of these extended windows while also considering these scenarios on a case-by-case basis.