Editors' ChoiceNeurology

A Stroke of Insight

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Science Translational Medicine  20 Mar 2013:
Vol. 5, Issue 177, pp. 177ec46
DOI: 10.1126/scitranslmed.3006107

For years, intravenous tissue plasminogen activator (t-PA) has been the only effective acute stroke therapy. However, the treatment landscape for acute ischemic stroke has evolved rapidly in the past decade. With the advent of neuroendovascular therapies, large vessel strokes are now being treated emergently with catheter-based mechanical revascularization strategies in much the same way as myocardial infarctions have been treated. Despite general acceptance within the community of neuroendovascular surgeons and stroke neurologists, no large, randomized controlled trials have evaluated the efficacy of these procedures.

The Interventional Management of Stroke (IMS) III investigators assessed whether a combined approach of intravenous t-PA and endovascular therapy is more effective than t-PA alone for patients with moderate-to-severe acute ischemic stroke. Although there were no safety concerns, the study was terminated early because the proportion of participants who achieved functional independence at 90 days did not differ between groups.

The authors rigorously controlled for critical study covariates and provided multiple prespecified subgroup analyses. None reached statistical significance. Perhaps dichotomous outcome stratification lessened the ability to discern treatment effect. In many cases, the objective of stroke therapy is to achieve incremental, rather than substantial, functional improvements.

As the authors state, this study highlights both the promise and limitations of endovascular acute stroke therapy. Time to intervention was somewhat longer in IMS III than in previous trials. The relationship between treatment latency and clinical effectiveness of intravenous t-PA, coupled with subgroup data from this trial, reaffirms the importance of minimizing treatment delays. The authors suggest that there may be potential for better outcomes in the subset of patients with proximal occlusions and severe stroke, but the sample size was too small for meaningful statistical inference. Perhaps most compelling is the discrepancy between implementation and execution of large-scale clinical trials and rapid technological advancements. The study team allowed for use of newer generation devices as the U.S. Food and Drug Administration approved them. However, by the time enrollment was terminated, the most frequently used devices were replaced or functionally obsolete. Promising future studies aimed at assessing the efficacy of endovascular acute stroke therapies should be guided by the important lessons learned from this investigation.

J. P. Broderick et al., Interventional Management of Stroke (IMS) III Investigators, Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N. Engl. J. Med. 368, 893–903 (2013). [Abstract]

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