Correspondence
Acute Ischemic Stroke
N Engl J Med 2007; 357:2203-2204November 22, 2007
- Article
To the Editor:
In the Clinical Practice article by van der Worp and van Gijn (Aug. 9 issue),1 the question of the age at which a patient could be selected for treatment with intravenous thrombolysis warrants further attention. According to the Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST) selection criteria,2 this treatment cannot be delivered to patients older than 80 years of age in routine clinical practice, but it has been shown that early treatment with recombinant tissue plasminogen activator (rt-PA) in carefully selected elderly patients is as safe and efficacious as it is in younger patients.3 A specific randomized trial is highly advisable before implementation of this therapy in routine clinical practice. The authors discuss the use of alteplase, but they do not discuss other fibrinolytic drugs (such as tenecteplase and desmoteplase)4 as being potential alternatives to this agent.
4 ReferencesAlberto Chiti, M.D.
Elisa Giorli, M.D.
Giovanni Orlandi, M.D.
Azienda Ospedaliero Universitaria Pisana, 56100 Pisa, Italy
g.orlandi@neuro. med. unipi. it 1
van der Worp HB ,van Gijn J . Acute ischemic stroke. N Engl J Med 2007;357:572-579
Full Text | Web of Science | Medline2
Wahlgren N ,Ahmed N ,Davalos A , et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007;369:275-282[Erratum, Lancet 2007;369:826.]
CrossRef | Web of Science | Medline3
Sylaja PN ,Cote R ,Buchan AM ,Hill MD . Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian Alteplase for Stroke Effectiveness Study. J Neurol Neurosurg Psychiatry 2006;77:826-829
CrossRef | Web of Science | Medline4
Adams HP Jr ,del Zoppo G ,Alberts MJ , et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation 2007;115:e478-e534
CrossRef | Web of Science | Medline
To the Editor:
In their article, van der Worp and van Gijn do not mention osmotic drugs such as mannitol to decrease edema and tissue damage in stroke. Massive brain edema and elevated intracranial pressure develop in some patients with stroke, and these patients are at very high risk for death. In patients thought to be at very high risk for cerebral edema, osmotic diuresis with mannitol can be effective.1,2
2 ReferencesNicola Mumoli, M.D.
Marco Cei, M.D.
Ospedale Civile Livorno, 57100 Livorno, Italy
nimumoli@tiscali.it 1
Brott T ,Bogousslavsky J . Treatment of acute ischemic stroke. N Engl J Med 2000;343:710-722
Full Text | Web of Science | Medline2
Adams HP Jr ,del Zoppo G ,Alberts MJ , et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation 2007;115:e478-e534
CrossRef | Web of Science | Medline
Author/Editor Response
Chiti and colleagues confuse the criteria for inclusion in the observational monitoring study SITS-MOST1 with the criteria for treatment with intravenous thrombolysis, which are provided in the most recent guidelines for the treatment of acute ischemic stroke.2 The criteria for treatment with intravenous thrombolysis are modeled on those of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial, and they define no upper age limit for intravenous thrombolysis. As we mentioned in our article, a post hoc subgroup analysis of the NINDS rt-PA Stroke Study showed no significant differences in the benefit from rt-PA among subgroups of patients categorized according to age.3 Unfortunately, the number of patients older than 80 years of age included in randomized trials of intravenous thrombolysis has been too small for definitive conclusions, but observational studies other than SITS-MOST have not shown an increase in the risk of intracranial hemorrhage among these patients.4
To our knowledge, the only published information on tenecteplase and desmoteplase for acute ischemic stroke comes from small phase 2 trials. For this reason, these agents cannot be recommended for use outside clinical trials.
With regard to the issue of osmotherapy raised by Mumoli and Cei, as we mentioned in our article, no medical therapy — including osmotherapy — has proved to be effective for the treatment of life-threatening edema in acute ischemic stroke. To our knowledge, there have been no randomized clinical trials testing this treatment strategy, and there is no other firm indication that osmotherapy improves functional outcome.5 As mentioned in the guidelines that Mumoli and Cei refer to, any recommendation regarding the use of osmotherapy for life-threatening edema is therefore based on expert opinion rather than evidence.2
5 ReferencesH. Bart van der Worp, M.D., Ph.D.
Jan van Gijn, F.R.C.P.
University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands
h.b. vanderworp@umcutrecht. nl 1
Wahlgren N ,Ahmed N ,Davalos A , et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007;369:275-282[Erratum, Lancet 2007;369:826.]
CrossRef | Web of Science | Medline2
Adams HP Jr ,del Zoppo G ,Alberts MJ , et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation 2007;115:e478-e534
CrossRef | Web of Science | Medline3
Generalized efficacy of t-PA for acute stroke: subgroup analysis of the NINDS t-PA Stroke Trial. Stroke 1997;28:2119-2125
CrossRef | Web of Science | Medline4
Sylaja PN ,Cote R ,Buchan AM ,Hill MD . Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian Alteplase for Stroke Effectiveness Study. J Neurol Neurosurg Psychiatry 2006;77:826-829
CrossRef | Web of Science | Medline5
Hofmeijer J ,Van der Worp HB ,Kappelle LJ . Treatment of space-occupying cerebral infarction. Crit Care Med 2003;31:617-625
CrossRef | Web of Science | Medline
