Reperfusion therapy with intravenous alteplase and endovascular therapy are effective treatments for selected patients with acute ischemic stroke. Guidelines for treatment are based upon randomized trials demonstrating substantial treatment effects for highly selected patients based on time from stroke onset and imaging features. However, patients beyond the current established guidelines might benefit with lesser but still clinically significant treatment effects. The STAIR (Stroke Treatment Academic Industry Roundtable) XI meeting convened a workgroup to consider the "outer limits" of reperfusion therapy by defining the current boundaries, and exploring optimal parameters and methodology for determining the outer limits. In addition to statistical significance, the minimum clinically important difference should be considered in exploring the limits of reperfusion therapy. Societal factors and quality of life considerations should be incorporated into assessment of treatment efficacy. The threshold for perception of benefit in the medical community may differ from that necessary for the Food and Drug Administration approval. Data from alternative sources such as platform trials, registries and large pragmatic trials should supplement randomized controlled trials to improve generalizability to routine clinical practice. Further interactions between industry and academic centers should be encouraged.
Keywords: ischemic stroke; magnetic resonance imaging; reperfusion; thrombolysis; tomography.