Skip to main content
AAN.com
Brief Communications
February 22, 2005
Letter to the Editor

Reasons for exclusion from thrombolytic therapy following acute ischemic stroke

February 22, 2005 issue
64 (4) 719-720

Abstract

Despite evidence for the efficacy of thrombolytic therapy in acute ischemic stroke, only 1 to 7% of patients receive this therapy. The authors sought to determine the reasons for exclusion from tissue plasminogen activator (tPA) in an acute setting and found avoidable causes in 18% of patients. Improvements in intrahospital coordination would increase the number of patients who might benefit from tPA treatment at the authors’ center.

Get full access to this article

View all available purchase options and get full access to this article.

References

1.
The National Institute of Neurological Disorders and Stroke rt-PA Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–1587.
2.
Wardlaw JM, Warlow CP, Counsell C. Systematic review of evidence on thrombolytic therapy for acute ischemic stroke. Lancet 1997;350:607–614.
3.
Koennecke HC, Nohr R, Leistner S, Marx P. Intravenous rtPA for ischemic stroke: team performance over time, safety, and efficacy in a single-centre, 2-year experience. Stroke 2001;32:1074–1078.
4.
Katzan IL, Furlan AJ, Lloyd LE, et al. Use of tissue plasminogen activator for acute ischemic stroke: the Cleveland area experience. JAMA 2000;283:1151–1158.
5.
Smith 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.
6. Spanish.
Rey A, Martí-Vilalta JL, Arboix A, Abellan MT. Latency in the hospital admittance of stroke. Rev Neurol 1995;23:272–275.
7.
O’Connor R, McGraw P, Edelsohn L. Thrombolytic therapy for acute ischemic stroke: why the majority of patients remain ineligible for treatment. Ann Emerg Med 1999;33:9–14.
8.
Barber PA, Zhang J, Demchuk AM, Hill MD, Buchan AM. Why are stroke patients excluded from RTPA therapy? An analysis of patient eligibility. Neurology 2001;56:1015–1020.
9.
Hacke W, Kaste M, Fieschi R, et al. for the Second European-Australasian Acute Stroke Study Investigators. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet 1998;352:1245–1251.
Letters to the Editor
12 May 2005
Reasons for exclusion from thrombolytic therapy following acute ischemic stroke
Pedro Schestatsky, Federal University of Rio Grande do Sul/Advisors of the Brazilian Ministry of Health
Pedro Schestatsky, Paulo Dornelles Picon

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.

12 May 2005
Reply to Schestatsky et al
Dolores Cocho, Servicio de Neurologia

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.

12 May 2005
Reasons for exclusion from thrombolytic therapy following acute ischemic stroke
Dawn O. Kleindorfer, University of Cincinnati
Pooja Khatri, Irene Katzan

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.

12 May 2005
Reply to Kleindorfer et al
Dolores Cocho, Servicio de Neurología

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.

Information & Authors

Information

Published In

Neurology®
Volume 64Number 4February 22, 2005
Pages: 719-720
PubMed: 15728300

Publication History

Published online: February 22, 2005
Published in print: February 22, 2005

Permissions

Request permissions for this article.

Authors

Affiliations & Disclosures

D. Cocho, MD
From the Cerebrovascular Unit, Departments of Neurology (Drs. Cocho, Belvís, Martí-Fàbregas, Molina-Porcel, Díaz-Manera, Aleu, Pagonabarraga, García-Bargo, and Martí-Vilalta) and Emergency (Dr. Mauri), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.
R. Belvís, MD
From the Cerebrovascular Unit, Departments of Neurology (Drs. Cocho, Belvís, Martí-Fàbregas, Molina-Porcel, Díaz-Manera, Aleu, Pagonabarraga, García-Bargo, and Martí-Vilalta) and Emergency (Dr. Mauri), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.
J. Martí-Fàbregas, MD
From the Cerebrovascular Unit, Departments of Neurology (Drs. Cocho, Belvís, Martí-Fàbregas, Molina-Porcel, Díaz-Manera, Aleu, Pagonabarraga, García-Bargo, and Martí-Vilalta) and Emergency (Dr. Mauri), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.
L. Molina-Porcel, MD
From the Cerebrovascular Unit, Departments of Neurology (Drs. Cocho, Belvís, Martí-Fàbregas, Molina-Porcel, Díaz-Manera, Aleu, Pagonabarraga, García-Bargo, and Martí-Vilalta) and Emergency (Dr. Mauri), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.
J. Díaz-Manera, MD
From the Cerebrovascular Unit, Departments of Neurology (Drs. Cocho, Belvís, Martí-Fàbregas, Molina-Porcel, Díaz-Manera, Aleu, Pagonabarraga, García-Bargo, and Martí-Vilalta) and Emergency (Dr. Mauri), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.
A. Aleu, MD
From the Cerebrovascular Unit, Departments of Neurology (Drs. Cocho, Belvís, Martí-Fàbregas, Molina-Porcel, Díaz-Manera, Aleu, Pagonabarraga, García-Bargo, and Martí-Vilalta) and Emergency (Dr. Mauri), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.
J. Pagonabarraga, MD
From the Cerebrovascular Unit, Departments of Neurology (Drs. Cocho, Belvís, Martí-Fàbregas, Molina-Porcel, Díaz-Manera, Aleu, Pagonabarraga, García-Bargo, and Martí-Vilalta) and Emergency (Dr. Mauri), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.
D. García-Bargo, MD
From the Cerebrovascular Unit, Departments of Neurology (Drs. Cocho, Belvís, Martí-Fàbregas, Molina-Porcel, Díaz-Manera, Aleu, Pagonabarraga, García-Bargo, and Martí-Vilalta) and Emergency (Dr. Mauri), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.
A. Mauri, MD
From the Cerebrovascular Unit, Departments of Neurology (Drs. Cocho, Belvís, Martí-Fàbregas, Molina-Porcel, Díaz-Manera, Aleu, Pagonabarraga, García-Bargo, and Martí-Vilalta) and Emergency (Dr. Mauri), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.
J. -L. Martí-Vilalta, MD
From the Cerebrovascular Unit, Departments of Neurology (Drs. Cocho, Belvís, Martí-Fàbregas, Molina-Porcel, Díaz-Manera, Aleu, Pagonabarraga, García-Bargo, and Martí-Vilalta) and Emergency (Dr. Mauri), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.

Notes

Address correspondence and reprint requests to Dr. Dolores Cocho, Servicio de Neurología, Hospital de la Santa Creu i Sant Pau, Avda. Sant Antoni M. Claret 167, E-08025 Barcelona, Spain; E-mail: [email protected]

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Comparing the Effectiveness of Intravenous Tissue Plasminogen Activator and Dual Antiplatelet Therapy in Patients With Minor Stroke: A Meta-Analysis, Cureus, (2023).https://doi.org/10.7759/cureus.46436
    Crossref
  2. Reasons for Exclusion From Intravenous Thrombolysis in Acute Ischemic Stroke: Experience From a Moroccan Stroke Unit, Cureus, (2023).https://doi.org/10.7759/cureus.33248
    Crossref
  3. Neuroinflammation in Ischemic Stroke: Inhibition of cAMP-Specific Phosphodiesterases (PDEs) to the Rescue, Biomedicines, 9, 7, (703), (2021).https://doi.org/10.3390/biomedicines9070703
    Crossref
  4. Intravenous Thrombolysis Benefits Mild Stroke Patients With Large-Artery Atherosclerosis but No Tandem Steno-Occlusion, Frontiers in Neurology, 11, (2020).https://doi.org/10.3389/fneur.2020.00340
    Crossref
  5. Progression of stroke deficits in patients presenting with mild symptoms: The underlying etiology determines outcome, PLOS ONE, 15, 4, (e0231448), (2020).https://doi.org/10.1371/journal.pone.0231448
    Crossref
  6. Comparison of outcome of patients with acute minor ischaemic stroke treated with intravenous t-PA, DAPT or aspirin, Stroke and Vascular Neurology, 6, 2, (187-193), (2020).https://doi.org/10.1136/svn-2019-000319
    Crossref
  7. Implementation of Best Practices—Developing and Optimizing Regional Systems of Stroke Care: Design and Methodology, American Heart Journal, 222, (105-111), (2020).https://doi.org/10.1016/j.ahj.2020.01.004
    Crossref
  8. Intravenous thrombolytic therapy for acute ischemic stroke in Hubei, China: a survey of thrombolysis rate and barriers, BMC Neurology, 19, 1, (2019).https://doi.org/10.1186/s12883-019-1418-z
    Crossref
  9. Absence of Collaterals is Associated with Larger Infarct Volume and Worse Outcome in Patients with Large Vessel Occlusion and Mild Symptoms, Journal of Stroke and Cerebrovascular Diseases, 28, 7, (1987-1992), (2019).https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.03.032
    Crossref
  10. Door to needle time and functional outcome for mild ischemic stroke over telestroke, Journal of Telemedicine and Telecare, 25, 6, (365-369), (2018).https://doi.org/10.1177/1357633X18774460
    Crossref
  11. See more
Loading...

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

Purchase this article to get full access to it.

Purchase Access, $39 for 24hr of access

View options

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

Share

Share

Share article link

Share