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Could thrombolytic approaches in acute stroke benefit from stringent selection criteria?

Nature Reviews Neurology volume 5, pages 138–139 (2009)Cite this article

Thirteen years after the New England Journal of Medicine published a pivotal study from the National Institute of Neurological Disorders and Stroke (NINDS),1 neurologists universally recognize that the thrombolytic agent alteplase (recombinant tissue plasminogen activator, or rtPA) is well tolerated and effective for the treatment of acute ischemic stroke. However, the use of intravenous rtPA has been limited by the requirement to administer it within 3 h of symptom onset. Recently, the European Cooperative Acute Stroke Study (ECASS) III demonstrated that this therapeutic window can be extended to 4.5 h.2 The safety and efficacy of thrombolytic therapy and other methods of recanalization that could be administered during a later time window must, therefore, be optimized. We consider that in addition to widening the therapeutic window, another important approach would be to narrow the selection criteria for thrombolysis, so as to reduce the number of patients at risk of thrombolytic complications.

Previous clinical trials that investigated intravenous thrombolysis administered in extended time windows after ischemic stroke—for example, Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS),3 and the European Cooperative Acute Stroke Study (ECASS) I and II4,5—have failed to show a significant benefit beyond 3 h. We postulate, however, that if some patients had been excluded from these trials, better results might have been obtained. A wider therapeutic window might, for example, be achieved using MRI and CT perfusion to select patients according to the amount of salvageable tissue in the ischemic penumbra. Some researchers have hypothesized that the diffusion–perfusion mismatch could be used to select the patients most likely to respond to thrombolysis,6 although this proposal remains to be investigated. The penumbra can be evaluated by use of echoplanar MRI, diffusion-weighted MRI and perfusion-weighted MRI. Diffusion-weighted MRI lesions are regions of cytotoxic edema that usually proceed to infarction, and mismatch between a large perfusion-weighted MRI lesion and small diffusion-weighted MRI lesion is thought to be a signature of the ischemic penumbra. The probability of infarction depends on the severity and duration of hypoperfusion in the ischemic penumbra. Imaging of the penumbra might allow selection of suitable candidates for thrombolysis beyond the 4.5 h time window, as well as for exclusion of patients who are unlikely to respond to this therapy.6 It might be argued that the selection of patients through such methods is more important than time to treatment if we are to achieve good clinical recovery and lower the risk of symptomatic intracerebral hemorrhage and mortality.7

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Authors and Affiliations

  1. AB Maulaz, M de Castro Ribeiro, R Londero and JOD Soares are Neurologists in the Moinhos de Vento Hospital Stroke Unit, Porto Alegre, Brazil.,

    Alexandre B Maulaz, Marlise de Castro Ribeiro, Renata Londero & José Otávio D Soares

  2. RT Martins is Neurologist-in-Chief of the Neurology Department of Hospital Nossa Senhora da Conceicao and a Neurologist in neurovascular diseases at Moinhos de Vento Hospital, Porto Alegre, Brazil.,

    Rodrigo Targa Martins

  3. JG Fernandes is Professor of the Department of Internal Medicine, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, and Director of the Institute of Education and research of the Moinhos de Vento Hospital Association, Porto Alegre, Brazil.,

    Jefferson Gomes Fernandes

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  1. Alexandre B Maulaz
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Correspondence to Alexandre B Maulaz.

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Maulaz, A., Martins, R., de Castro Ribeiro, M. et al. Could thrombolytic approaches in acute stroke benefit from stringent selection criteria?. Nat Rev Neurol 5, 138–139 (2009). https://doi.org/10.1038/ncpneuro1048

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