Reflection on the Past, Present, and Future of Thrombolytic Therapy for Acute Ischemic Stroke

More than 25 years have passed since the US Food and Drug Administration approved IV recombinant tissue plasminogen activator (alteplase) for the treatment of acute ischemic stroke. This landmark decision brought a previously untreatable disease into a new therapeutic landscape, providing inspiration for clinicians and hope to patients. Since that time, the use of alteplase in the clinical setting has become standard of care, continually improving with quality measures such as door-to-needle times and other metrics of specialized stroke unit care. The past decade has seen more widespread use of alteplase in the prehospital setting with mobile stroke units and telestroke and beyond initial time windows via the use of CT perfusion or MRI. Simultaneously, the position of alteplase is being challenged by new lytics and by the concept of its bypass altogether in the era of endovascular therapy. We provide an overview of alteplase, including its earliest trials and how they have shaped the current therapeutic landscape of ischemic stroke treatment, and touch on new frontiers for thrombolytic therapy. We highlight the critical role of thrombolytic therapy in the past, present, and future of ischemic stroke care.

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Abstract 215: Differing Perspectives Between Physicians, Patients And Caregivers On The Value Of An Individualized Estimate Of The Benefits Of Thrombolysis At The Time Of Acute Ischemic Stroke: Designing The Resolve (Rapid Evaluation for Stroke Outcomes using Lytics in Vascular Event) Decision Aid

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.6.suppl_1.a215 ◽

2013 ◽

Vol 6 (suppl_1) ◽

Author(s):

Carole J Decker ◽

Emily Chhatriwalla ◽

Brian Garavalia ◽

John A Spertus ◽

Er Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Qualitative Interviews ◽

Treatment Decision ◽

Recombinant Tissue Plasminogen Activator ◽

Active Role ◽

Cultural Barriers ◽

Emergency Physicians ◽

Stroke Treatment ◽

Risks And Benefits

Background: Explaining the risks and benefits of recombinant tissue plasminogen activator (rt-PA) occurs in a hurried conversation in the emergency department and may not be fully grasped by patients and their caregivers. Risk models describing the heterogeneity of benefits from rt-PA in acute ischemic stroke (AIS) have been created, but are not used in routine clinical practice. To develop a tool (RESOLVE) for modeling each patient’s benefits and risks for rt-PA, we conducted qualitative interviews with survivors, their caregivers and emergency physicians to inform the design and improve usability. Methods: A multidisciplinary research team conducted qualitative research through 10 focus groups of survivors and caregivers. We obtained feedback on their preferred role, desired information and their impressions of alternative formats for presenting risk and benefits. Three emergency physicians from 2 sites have been interviewed (with >15 additional physician interviews being currently conducted, the results of which will supplement these preliminary data at the time of presentation). Results: Survivors and caregivers (63 participants: 39 stroke survivors; 43% male) express a need for more information, including specific risks and benefits to treatment. In general, both groups desired an active role in the acute stroke treatment decision. In contrast, the initial physician interviews indicated a hesitancy to provide NINDS data to patients and caregivers, skepticism of the existing data and cultural barriers to the use of rt-PA in AIS, the latter acquired through residency training or the opinions of their clinical colleagues. The interviewed clinicians, however, felt more positive about using rt-PA when a neurologist was readily available to support the decision. Conclusions: Preliminary findings suggest reluctance by emergency physicians to share data about the benefits of rt-PA to stroke patients and their caregivers, despite the desire of the latter for such information. While the additional planned interviews will be needed to confirm these findings, preliminary insights suggest a compelling need to overcome the reticence of emergency physicians to use clinical data to better engage patients in making a shared decision about rt-PA in AIS.

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Thrombolytic Therapy for Acute Ischemic Stroke: The CAEP Position Statement: another perspective

CJEM ◽

10.1017/s1481803500005509 ◽

2001 ◽

Vol 3 (03) ◽

pp. 180-182

Author(s):

Michael D. Hill ◽

Gordon J. Gubitz ◽

Stephen J. Phillips ◽

Alastair M. Buchan

Keyword(s):

Ischemic Stroke ◽

Thrombolytic Therapy ◽

Acute Ischemic Stroke ◽

Randomized Trials ◽

Recombinant Tissue Plasminogen Activator ◽

Position Statement ◽

Emergency Physicians ◽

Canadian Association ◽

Tissue Plasminogen ◽

Areas Of Concern

The cautiously-worded Position Statement recently issued by the Canadian Association of Emergency Physicians (see Appendix 1) regarding the use of intravenous recombinant tissue-plasminogen activator (tPA, alteplase) for acute ischemic stroke underscores the reality that many physicians in Canada have been reluctant to embrace this therapy. Much of the caution expressed in the CAEP document is related to 2 major areas of concern: evidence of efficacy (i.e., did tPA really “prove” itself in randomized trials?) and effectiveness (i.e., are the trial results generalizable to everyday practice?). While we support the development of documents that help to clarify controversial treatments, and agree with much of what is presented in the CAEP Position Statement, we offer the following comments.

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Barriers for acute ischemic stroke treatment using recombinant tissue plasminogen activator in Mansoura Emergency Hospital: prehospital and inhospital delay factors

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.4103/1110-1083.202377 ◽

2016 ◽

Vol 53 (4) ◽

pp. 263 ◽

Cited By ~ 1

Author(s):

Mohammad Abu-Hegazy ◽

Ibrahim Elmenshawi ◽

Mohamed Saad

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Recombinant Tissue Plasminogen Activator ◽

Stroke Treatment ◽

Emergency Hospital ◽

Tissue Plasminogen

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Clinical application value of brain CT perfusion imaging in the treatment of acute ischemic stroke thrombolytic therapy

Experimental and Therapeutic Medicine ◽

10.3892/etm.2019.7431 ◽

2019 ◽

Cited By ~ 2

Author(s):

Shiming Xu ◽

Li Wang ◽

Lidong Zhao

Keyword(s):

Ischemic Stroke ◽

Thrombolytic Therapy ◽

Acute Ischemic Stroke ◽

Clinical Application ◽

Perfusion Imaging ◽

Ct Perfusion ◽

Brain Ct ◽

Ct Perfusion Imaging

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Tenecteplase for Acute Ischemic Stroke Treatment

Seminars in Neurology ◽

10.1055/s-0040-1722722 ◽

2021 ◽

Vol 41 (01) ◽

pp. 028-038

Author(s):

Alison E. Baird ◽

Richard Jackson ◽

Weijun Jin

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Plasminogen Activator ◽

Plasminogen Activator Inhibitor ◽

Recombinant Tissue Plasminogen Activator ◽

The United States ◽

Similar Efficacy ◽

Plasminogen Activator Inhibitor 1 ◽

Stroke Treatment ◽

United States Food

AbstractThe introduction of thrombolytic therapy in the 1990s has transformed acute ischemic stroke treatment. Thus far, intravenous recombinant tissue plasminogen activator (rt-PA) also known as alteplase is the only thrombolytic proven to be efficacious and approved by the United States Food and Drug Administration. But the thrombolytic agent tenecteplase (TNK) is emerging as a potential replacement for rt-PA. TNK has greater fibrin specificity, slower clearance, and higher resistance to plasminogen activator inhibitor-1 than rt-PA. Hence, TNK has the potential to provide superior lysis with fewer hemorrhagic complications. Also, easier bolus-only administration makes TNK a very practical rt-PA alternative. In several clinical trials, TNK has shown similar efficacy and safety to rt-PA, and the potential to be at least noninferior to rt-PA in some settings. TNK may be superior to rt-PA for reperfusing large vessel occlusions in patients with salvageable penumbra, although this has not yet translated to improved clinical outcomes. Further phase 3 studies are in progress comparing rt-PA with TNK for acute ischemic stroke during the first 4.5 hours. Studies are also in progress to evaluate the use of TNK for extended applications, such as wake-up stroke.

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PREDICTORS THE RISK OF SYMPTOMATIC INTRACEREBRAL HEAMORHAGE AFTER THROMBOLYTIC THERAPY WITH RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR IN ACUTE ISCHEMIC STROKE

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2017.2.11 ◽

2017 ◽

pp. 64-67

Author(s):

Dinh Thuyen Nguyen ◽

Duy Ton Mai ◽

Viet Phuong Dao ◽

Anh Tuan Nguyen

Keyword(s):

Ischemic Stroke ◽

Thrombolytic Therapy ◽

Acute Ischemic Stroke ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Recombinant Tissue Plasminogen Activator ◽

Brain Ct ◽

Tissue Plasminogen ◽

History Of ◽

Stroke Thrombolysis

Objective: to evaluate predictors the risk of symptomatic intracerebral heamorrhage after thrombolytic therapy with recombinant tissue plasminogen activator in acute ischemic stroke. Methods: observative study on 54 patients with acute ischemic stroke at Emergency Department, Bach Mai hospital from 01/2010 to 10/2016. Results: Predictors the risk of symptomatic intracerebral heamorrhage were: age above 70 (OR 2,76; 95% CI 0,73 – 10,52; p = 0,12), time from onset to treatment (OR 1,03; 95% CI 0,34 – 3,13; p = 0,95), systolic blood pressure ≥ 140 mmHg (OR 2,0; 95% CI 0,61 – 6,51; p = 0,24), NIHSS score above 12 (OR 3,13; 95% CI 0,63 – 15,51; p = 0,138), glycemia above 10 mmol/l (OR 8,94; 95% CI 1,51 – 51,73; p = 0,003), fibrillation atrial (OR 1,49; 95% 0,49 – 4,56; p = 0,33), history of diebete (OR 6,4; 95% CI 0,67 – 61,03; p = 0,06), history of anticoagulation (OR 1,07; 95% CI 0,22 – 5,11; p = 0,63), history of cerebral infarction (OR 1,49; 95% CI 0,183 – 12,184; p = 0,707), sign of early brain CT (OR 6,14; 95% CI 1,01 – 39,93; p = 0,048). Conclusion: glucose above 10 mmol/l and sign of early brain CT were predictors the risk of symptomatic intracerebral heamorrhage after thrombolytic therapy with recombinant tissue plasminogen activator in acute ischemic stroke. Key words: stroke, thrombolysis, predictor, heamorrhage conversion

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Thrombolytic Therapy for Acute Ischemic Stroke: What Cardiac Physicians Need to Know

Asian Cardiovascular and Thoracic Annals ◽

10.1177/021849239600400402 ◽

1996 ◽

Vol 4 (4) ◽

pp. 196-200

Author(s):

Roger L White

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Ischemic Stroke ◽

Thrombolytic Therapy ◽

Acute Ischemic Stroke ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Recombinant Tissue Plasminogen Activator ◽

Current Status ◽

Tissue Plasminogen

The current status of thrombolytic therapy for acute ischemic stroke is reviewed in relation to early work and to the use of thrombolytic agents in acute myocardial infarction. The case of a patient treated with recombinant tissue plasminogen activator for acute ischemic stroke is described to illustrate the improvement in outcome that can be achieved with this therapy in selected patients. A number of recommendations are included for cardiologists on the use of plasminogen activator in acute ischemic stroke regarding the timing, dosage, selection, and monitoring of patients.

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