In reply

Abstract

Thank you for the opportunity to answer the letter of Dr. Durston. He raised a few points that deserve to be challenged. We do not advocate thrombolysis in stroke mimics but report that when we have mistakenly treated stroke mimic patients with thrombolysis, no harm has been done. The results of the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) trial have been denied also, but a reanalysis conducted by an independent committee has reached the same conclusions as the National Institute of Neurological Disorders and Stroke rt-PA investigators.1Ingall T.J. O'Fallon W.M. Asplund K. et al.Findings from the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial.Stroke. 2004; 35: 2418-2424Crossref PubMed Scopus (200) Google Scholar All European Cooperative Acute Stroke trials were sponsored by Boehringer Ingelheim. The results of all those trials were published, although European Cooperative Acute Stroke and European Cooperative Acute Stroke 2 were negative and only European Cooperative Acute Stroke 3 was positive.2Hacke W. Kaste M. Fieschi C. et al.Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke The European Cooperative Acute Stroke Study (ECASS).JAMA. 1995; 274: 1017-1025Crossref PubMed Scopus (2878) Google Scholar, 3Hacke W. Kaste M. Fieschi C. et al.Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II) Second European-Australasian Acute Stroke Study Investigators.Lancet. 1998; 352: 1245-1251Abstract Full Text Full Text PDF PubMed Scopus (2809) Google Scholar, 4Hacke W. Kaste M. Bluhmki E. et al.ECASS InvestigatorsThrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.N Engl J Med. 2008; 359: 1317-1329Crossref PubMed Scopus (4904) Google Scholar The first pooled analysis verified that thrombolysis improves the outcome of treated patients up to 3 hours compared with placebo-treated controls,5ATLANTIS; ECASS; NINDS rt-PA Study Group InvestigatorsAssociation of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials.Lancet. 2004; 363: 768-774Abstract Full Text Full Text PDF PubMed Scopus (2169) Google Scholar and the second pooled analysis verified that this is the case up to 4 and a half hours.6Lees K.R. Bluhmki E. von Kummer R. et al.ECASS; ATLANTIS; NINDS; EPITHET rt-PA Study GroupTime to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials.Lancet. 2010; 375: 1695-1703Abstract Full Text Full Text PDF PubMed Scopus (1621) Google Scholar The third pooled analysis is in the planning stage, and once the results of Third International Stroke Trial are available, an analysis of all randomized rt-PA trials will be executed again. With a large patient population, the third pooled analysis will reveal how long the window for thrombolysis is open. None of the pooled analyses has commercial sponsors. Until the article has been published, it is reasonable to provide thrombolysis to eligible patients after excluding those with contraindications to thrombolysis, such as stroke mimics. The first Safe Implementation of Thrombolysis in Stroke registry article revealed that thrombolysis is as safe and effective up to 3 hours in clinical routine as it is in randomized controlled trials,7Wahlgren N. Ahmed N. Dávalos A. et al.SITS InvestigatorsThrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study.Lancet. 2007; 369: 275-282Abstract Full Text Full Text PDF PubMed Scopus (1729) Google Scholar and the second Safe Implementation of Thrombolysis in Stroke article revealed that this is the case up to 4 and a half hours.8Ahmed N. Wahlgren N. Grond M. et al.SITS InvestigatorsImplementation and outcome of thrombolysis with alteplase 3-4.5 h after an acute stroke: an updated analysis from SITS-ISTR.Lancet Neurol. 2010; 9: 866-874Abstract Full Text Full Text PDF PubMed Scopus (243) Google Scholar It is certain that those 2 analyses have included stroke mimics because human beings make mistakes; however, they also verify that benefits of thrombolysis overcome its risks. If an emergency physician is not sure whether to treat a stroke patient with rt-PA, he or she should consult a stroke neurologist and do it quickly while there is still is time to improve the outcome of the patient. Thank you for the opportunity to answer the letter of Dr. Durston. He raised a few points that deserve to be challenged. We do not advocate thrombolysis in stroke mimics but report that when we have mistakenly treated stroke mimic patients with thrombolysis, no harm has been done. The results of the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) trial have been denied also, but a reanalysis conducted by an independent committee has reached the same conclusions as the National Institute of Neurological Disorders and Stroke rt-PA investigators.1Ingall T.J. O'Fallon W.M. Asplund K. et al.Findings from the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial.Stroke. 2004; 35: 2418-2424Crossref PubMed Scopus (200) Google Scholar All European Cooperative Acute Stroke trials were sponsored by Boehringer Ingelheim. The results of all those trials were published, although European Cooperative Acute Stroke and European Cooperative Acute Stroke 2 were negative and only European Cooperative Acute Stroke 3 was positive.2Hacke W. Kaste M. Fieschi C. et al.Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke The European Cooperative Acute Stroke Study (ECASS).JAMA. 1995; 274: 1017-1025Crossref PubMed Scopus (2878) Google Scholar, 3Hacke W. Kaste M. Fieschi C. et al.Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II) Second European-Australasian Acute Stroke Study Investigators.Lancet. 1998; 352: 1245-1251Abstract Full Text Full Text PDF PubMed Scopus (2809) Google Scholar, 4Hacke W. Kaste M. Bluhmki E. et al.ECASS InvestigatorsThrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.N Engl J Med. 2008; 359: 1317-1329Crossref PubMed Scopus (4904) Google Scholar The first pooled analysis verified that thrombolysis improves the outcome of treated patients up to 3 hours compared with placebo-treated controls,5ATLANTIS; ECASS; NINDS rt-PA Study Group InvestigatorsAssociation of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials.Lancet. 2004; 363: 768-774Abstract Full Text Full Text PDF PubMed Scopus (2169) Google Scholar and the second pooled analysis verified that this is the case up to 4 and a half hours.6Lees K.R. Bluhmki E. von Kummer R. et al.ECASS; ATLANTIS; NINDS; EPITHET rt-PA Study GroupTime to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials.Lancet. 2010; 375: 1695-1703Abstract Full Text Full Text PDF PubMed Scopus (1621) Google Scholar The third pooled analysis is in the planning stage, and once the results of Third International Stroke Trial are available, an analysis of all randomized rt-PA trials will be executed again. With a large patient population, the third pooled analysis will reveal how long the window for thrombolysis is open. None of the pooled analyses has commercial sponsors. Until the article has been published, it is reasonable to provide thrombolysis to eligible patients after excluding those with contraindications to thrombolysis, such as stroke mimics. The first Safe Implementation of Thrombolysis in Stroke registry article revealed that thrombolysis is as safe and effective up to 3 hours in clinical routine as it is in randomized controlled trials,7Wahlgren N. Ahmed N. Dávalos A. et al.SITS InvestigatorsThrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study.Lancet. 2007; 369: 275-282Abstract Full Text Full Text PDF PubMed Scopus (1729) Google Scholar and the second Safe Implementation of Thrombolysis in Stroke article revealed that this is the case up to 4 and a half hours.8Ahmed N. Wahlgren N. Grond M. et al.SITS InvestigatorsImplementation and outcome of thrombolysis with alteplase 3-4.5 h after an acute stroke: an updated analysis from SITS-ISTR.Lancet Neurol. 2010; 9: 866-874Abstract Full Text Full Text PDF PubMed Scopus (243) Google Scholar It is certain that those 2 analyses have included stroke mimics because human beings make mistakes; however, they also verify that benefits of thrombolysis overcome its risks. If an emergency physician is not sure whether to treat a stroke patient with rt-PA, he or she should consult a stroke neurologist and do it quickly while there is still is time to improve the outcome of the patient. Stroke Mimics and Intravenous ThrombolysisAnnals of Emergency MedicineVol. 60Issue 2PreviewIn their report on stroke mimics and intravenous thrombolysis, Artto et al1 conclude that patients with stroke mimics were infrequent in their study and that none of the 14 patients with diagnoses of stroke mimic was harmed by receiving tissue plasminogen activator (tPA).1 They acknowledge a potential bias in their study, though, toward misclassifying stroke mimics as actual strokes, noting that “…the diagnosis might have been biased toward ischemic stroke because making an alternative diagnosis after applying intravenous thrombolysis may have been difficult.” Artto et al1 state in the introduction to their article that 5 other small studies, including a total of 145 stroke mimic cases treated with tPA, also reported no symptomatic intracranial hemorrhage in such patients. Full-Text PDF