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BRIEF COMMUNICATIONS: D. Cocho, R. Belvís, J. Martí-Fàbregas, L. Molina-Porcel, J. Díaz-Manera, A. Aleu, J. Pagonabarraga, D. García-Bargo, A. Mauri, and J. -L. Martí-Vilalta Reasons for exclusion from thrombolytic therapy following acute ischemic stroke Neurology 2005; 64: 719-720 [Abstract] [Full text] [PDF]

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Reasons for exclusion from thrombolytic therapy following acute ischemic stroke

Dawn O. Kleindorfer, Pooja Khatri, Irene Katzan   (12 May 2005)

Reply to Kleindorfer et al

Dolores Cocho   (12 May 2005)

Reply to Schestatsky et al

Dolores Cocho   (12 May 2005)

Reasons for exclusion from thrombolytic therapy following acute ischemic stroke

Pedro Schestatsky, Pedro Schestatsky, Paulo Dornelles Picon   (12 May 2005)

Reasons for exclusion from thrombolytic therapy following acute ischemic stroke 12 May 2005
Dawn O. Kleindorfer, University of Cincinnati 231 Albert Sabin Way, Cincinnati, OH, Pooja Khatri, Irene Katzan Send Correspondence to journal: Re: Reasons for exclusion from thrombolytic therapy following acute ischemic stroke dawn.kleindorfer{at}uc.edu Dawn O. Kleindorfer, et al.	We welcome this important discussion regarding exclusions from thrombolytic therapy in acute ischemic stroke. [1] We agree that rt-PA is not used enough for the treatment of ischemic stroke, especially in the US, which has had drug approval longer than in Europe. The authors reported that approximately half of their stroke patients arrived at their hospital within 3 hours from symptom onset. We have studied arrival times extensively within the Greater Cincinnati/Northern Kentucky population of 1.3 million [2], a nine-hospital system in Cleveland [3], as well as a U.S. state-based stroke registry, encompassing 98 hospitals of varying size and character (personal communication, Reeves et al, 2005). We found that only 15-22% of ischemic stroke patients arrive within three hours. More importantly, comparing arrival times in 1993 and 1999, the percentage of patients arriving within three hours only increased from 18% to 20% [4] , despite numerous national and local public awareness campaigns. Based on our data, expansion of the time window for acute treatment to eight hours is not likely to result in significantly increased rates of acute treatment, as only 8% of all ischemic stroke patients arrive within 3-8 hours post- stroke. [4] We have also investigated characteristics of patients arriving promptly after stroke onset but not treated with thrombolytic therapy. In the Ohio Coverdell registry [5], only 171 of the 1066 ischemic strokes (16%) presented within 2 hours of symptom onset. Of those, 20 received rt- PA, and 69 had no recorded contraindication. Patients who did not receive tPA in this group were more likely to be at small hospitals, community settings, or hospitals without stroke team involvement. The most commonly listed exclusions for these non-treated patients were time (despite arriving early) and mild stroke severity. Therefore, while we agree that it is extremely important to minimize delays within the hospital system, we would like to emphasize that the delay in patient arrival to the ED remains the most important exclusion for rt-PA. This has recently been confirmed by the California Coverdell registry, published in the same issue of Neurology, which found that increasing early arrival of stroke patients would hypothetically increase thrombolytic treatment by orders of magnitude more than other interventions, including the presence of stroke teams and prompt medical evaluation. [6]. Public awareness regarding stroke warning signs and plans of action require more focused study, so that more stroke patients can benefit from rt-PA. References 1. Cocho D, Belvís R, Martí-Fàbregas J, et al. Reasons for exclusion from thrombolytic therapy following acute ischemic stroke Neurology 2005; 64: 719-720 2. Kleindorfer D, Kissela B, Schneider A, et al. Eligibility for recombinant tissue plasminogen activator in acute ischemic stroke: a population-based study. Stroke 2004; 35:e27-9. 3. Katzan IL, Hammer MD, Hixson ED, Furlan AJ, Abou-Chebl A, Nadzam DM. Utilization of intravenous tissue plasminogen activator for acute ischemic stroke. Arch Neurol 2004; 61:346-50. 4. Kleindorfer D, Alwell, K, Khoury, et al. Temporal Trends in Emergency Department Arrival Times for Acute Ischemic Stroke: A Population-Based Study. Stroke 2005; 36:494. 5. Khatri P, Kleindorfer D, Moomaw C, et al. Characteristics of Stroke Patients without rt- PA Treatment Despite Prompt Presentation. Accepted for poster presentation, 57th American Academy of Neurology 2005. 6. California Acute Stroke Pilot Registry Investigators. Prioritizing interventions to improve rates of thrombolysis for ischemic stroke. Neurology 2005; 64:654-9. The authors have no conflicts of interest to declare.
Reply to Kleindorfer et al 12 May 2005
Dolores Cocho, Servicio de Neurología Hospital de la Santa Creu i Sant Pau, Avda. Sant Antoni M. Claret 167, E-08025 Barcelona, Spain Send Correspondence to journal: Re: Reply to Kleindorfer et al dcocho{at}hsp.santpau.es Dolores Cocho	We thank Dr. Kleindorfer et al for their comments. We agree that the delay in patients’ arrival at the emergency department is the main reason for exclusion from t-PA. In our study, 44% of stroke patients arrived within 3 hours of stroke onset. These results are discordant with the percentages reported in some studies (18-20%)[1,2] and in agreement with others. [3,4] One explanation for this high percentage may be that the results are those of a single institution, geographically situated within the Barcelona city center, with a pre-hospital stroke code system which was implemented 6 years ago. [5]. However, our main finding is that although a high percentage of patients reached the hospital within 3 hours of symptom onset, t-PA treatment was administered in only 7%, and 18% were excluded for avoidable reasons. The delay in hospital arrival could be shortened through national and local awareness campaigns, but if the patients are not treated promptly on hospital arrival due to intra- hospital delays or other avoidable reasons, such campaigns will be ineffective. It is important that each center analyzes its reasons for excluding patients from thrombolytic therapy. We agree with Dr Kleindorfer et al that the presence of stroke teams and prompt medical evaluation could increase the application of thrombolytic treatment. References 1. Kleindorfer D, Kissela B, Schneider A, et al. Eligibility for recombinant tissue plasminogen activator in acute ischemic stroke: a population-based study. Stroke 2004;35:e27-9. 2. Katzan IL, Hammer MD, Hixson ED, Furlan AJ, Abou-Chebl A, Nadzam DM. Utilization of intravenous tissue plasminogen activator for acute ischemic stroke. Arch Neurol 2004;61:346-50. 3. Smitch MA, Doliszny KM, Shahar E, McGovern PG, Arnett DK, Luepker RV. Delayed hospital arrival for acute stroke: the Minnesota Stroke Survey. Arch Intern Med 1998;129:190-196. 4. Morris DL, Rosamond W, Madden K, Schultz C, Hamilton S. Prehospital and emergency department delays after acute stroke: the Genentech Stroke Presentation Survey. Stroke. 2000;31(11):2585-90. 5. Belvis R, Cocho D, Marti-Fabregas J, et al. Benefits of a prehospital stroke code system. Feasibility and efficacy in the first year of clinical practice in Barcelona, Spain. Cerebrovasc Dis. 2005;19(2):96-101.
Reply to Schestatsky et al 12 May 2005
Dolores Cocho, Servicio de Neurologia Hospital de la Santa Creu i Sant Pau, Avda. Sant Antoni M. Claret 167, E-08025 Barcelona, Spain Send Correspondence to journal: Re: Reply to Schestatsky et al dcocho{at}hsp.santpau.es Dolores Cocho	We thank Dr. Schestatsky et al for their comments. We agree that the narrow therapeutic window is the main limitation for intravenous t-PA treatment and that intra-arterial prourokinase is a correct alternative for patients arriving at a hospital more than 3 hours after stroke onset. However, in our center this therapy is not always available and few patients can benefit from this treatment. The main objective in our study was to analyze the reasons for exclusion from intravenous t-PA in order to increase the number of eligible patients. Although intra-arterial prourokinase should be considered in randomized controlled trials in patients after 3 hours stroke onset, other treatments may also be adequate. Mechanical embolus removal [1], for example, has a rate of 41-48% of recanalizations [1,2,3] in the first 6-8 hours of stroke onset as compared to 66% with intra-arterial prourikinase [4], and a rate of symptomatic intracerebral hemorrhage of 2.9% as compared to 10%. We agree that further randomized controlled studies are needed to investigate the benefits of the new treatments which are becoming available. References 1. Gobin P, Starkman S, Duckwiler G, et al. MERCI 1. A phase 1 study of Mechanical Embolus Removal in Cerebral ischemia. Stroke 2004;35:2848- 54. 2. Berlis A, Lustsep H, Barnwell S, et al. Mechanical thrombolysis in acute ischemic stroke with endovascular photoacoustic recanalization. Stroke 2004;35:1112-16. 3. Wikholm G. Transarterial embolectomy in acute stroke. AJNR Am J Neuroradiol 2003;24:892-94. 4. Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT-II study: a randomized controlled trial. Prolyse in acute Cerebral Thromboembolism. JAMA 1999;282:2003-11.
Reasons for exclusion from thrombolytic therapy following acute ischemic stroke 12 May 2005
Pedro Schestatsky, Federal University of Rio Grande do Sul/Advisors of the Brazilian Ministry of Health Rua São Francisco 906/703 ZIP 90620-070 Porto Alegre-Brazil, Pedro Schestatsky, Paulo Dornelles Picon Send Correspondence to journal: Re: Reasons for exclusion from thrombolytic therapy following acute ischemic stroke lonfra{at}hotmail.com Pedro Schestatsky, et al.	We believe that another important issue should be included in the discussion of the Cocho et al article. [1] There was a narrow therapeutic window of intravenous t-PA in patients with acute ischemic stroke in the Cocho et al study (only 44,8% were eligible for intravenous t-PA therapy). Further studies using more adequate designs (i.e, randomized controlled trials), are needed to clarify the role of this thrombolytic agent in the intra-arterial approach after 3 hours. Prourokinase is currently the only drug adequately tested in intra-arterial treatment for acute ischemic stroke [2] and should be considered as the gold standard for new treatments. However, it is not easily available in most stroke unit centers around the world. References 1. Cocho D, Belvis R, Marti-Fabregas J, et al. Reasons for exclusion from thrombolytic therapy following acute ischemic stroke. Neurology. 2005 Feb 22;64(4):719-20. 2. Furlan A, Higashida R, Wechsler L, et al. Intra- arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999 Dec 1;282:2003-11.