tPA for Acute Ischemic Stroke and Its Controversies: A Review

Background and Purpose:Although neurologists consider intravenous tissue plasminogen activator (tPA) to be standard of care in the treatment of patients with acute ischemic stroke, its use remains contentious within the broader medical community, and particularly among emergency physicians. Why might this be? We provide a historical context to this ongoing controversy by reviewing how neurologists have conceptualized the acute stroke and its treatment, with the aim of bridging this gap.Methods:Based on historical sources in the Mackie Family History of Neuroscience Collection at the University of Calgary, as well as online resources, we trace the evolution of the concept of the “acute stroke,” which has come to mean a stroke that is potentially treatable with tPA. We frame this conceptualization in relation to historical “building blocks” in anatomy, pathology, and physiology. We then use these building blocks to explain why neurologists understand tPA to be effective and why emergency physicians often do not.Results and Conclusions:Arguments against the use of tPA reiterate 20-year-old concerns about its efficacy and safety. We believe these persistent concerns can be framed as a lack of understanding of the “building blocks” upon which neurologists’ conception of tPA is built. Our view suggests that the way forward to bridge the gap between neurology and other disciplines is not to conduct more trials but to offer a shared conceptualization of the trials already completed and of the intellectual tradition from which they emerged.

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Abstract P201: Octogenarian and Nonagenarian Outcomes Among Acute Ischemic Stroke Patients

Stroke ◽

10.1161/str.52.suppl_1.p201 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

RAJAN R GADHIA ◽

Farhaan S Vahidy ◽

Tariq Nisar ◽

Destiny Hooper ◽

David Chiu ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Stroke ◽

Acute Ischemic Stroke ◽

Combined Treatment ◽

Stroke Patients ◽

Stroke Treatment ◽

Intravenous Tissue Plasminogen Activator ◽

Significant Difference ◽

Acute Stroke Treatment ◽

Iv Tpa

Objective: Most acute stroke treatment trials exclude patients above the age of 80. Given the clear benefit of revascularization with intravenous tissue plasminogen activator (IV tPA) and mechanical thrombectomy (MT), we sought to assess functional outcomes in patients treated above the age of 80. Methods: We conducted a review of all patients admitted to Houston Methodist Hospital between January 2019 and August 2020 with an acute ischemic stroke (AIS) presentation[MOU1] for whom premorbid, discharge, and 90 day modified Rankin Scale scores were available. Patients were categorized by acute stroke treatment (IV tPA, MT, both or none[MOU2] ). mRS values were assessed during admission prior to discharge and at 90 days post stroke event. A delta mRS (Discharge vs. 90-day [MOU3] ) was defined and grouped as no change, improved, or worsened to assess overall functional disability in regards to the index stroke presentation. Results: A total of 865 patients with AIS presentation were included, of whom 651 (75.3%) were <80 years and 214 (24.7%) were > 80 years of age at presentation. A total of 208 patients received IV tPA, 176 underwent revascularization with MT only, 71 had both treatments, and 552 had no acute intervention. In patients >80 yrs who had no acute stroke intervention. mRS improvement was noted in 71.4% compared to 54.1% observed in those patients <80 years. Among patients who received IV tPA, 81.5% of > 80 years improved vs. 61.6% in the younger cohort. A similar trend was noted in the MT and combined treatment groups (76.2% vs. 71.2% and 78.6% vs. 79.3%, respectively). Conclusion: Based on our cohort of acute stroke patients, there was no significant difference in outcomes (as measured by delta mRS) for octogenarians and nonagenarians when compared to younger patients. There was a trend towards improvement in the elderly patients. Chronological age by itself may be an insufficient predictor of functional outcome among stroke patients and age cutoffs for enrollment of patients in acute stroke trials may need additional considerations.

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Endovascular treatment of acute ischemic stroke: the end or just the beginning?

Neurosurgical FOCUS ◽

10.3171/2013.10.focus13374 ◽

2014 ◽

Vol 36 (1) ◽

pp. E5 ◽

Cited By ~ 29

Author(s):

Maxim Mokin ◽

Alexander A. Khalessi ◽

J Mocco ◽

Giuseppe Lanzino ◽

Travis M. Dumont ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Stroke ◽

Acute Ischemic Stroke ◽

Randomized Trials ◽

Intravenous Thrombolysis ◽

Lessons Learned ◽

Neurological Deficits ◽

Medical Community ◽

Current Status

Various endovascular intraarterial approaches are available for treating patients with acute ischemic stroke who present with severe neurological deficits. Three recent randomized trials—Interventional Management of Stroke (IMS) III, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE), and Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke (SYNTHESIS Expansion)—evaluated the efficacy of endovascular treatment of acute ischemic stroke and, after failing to demonstrate any significant clinical benefit of endovascular therapies, raised concerns and questions in the medical community regarding the future of endovascular treatment for acute ischemic stroke. In this paper, the authors review the evolution of endovascular treatment strategies for the treatment of acute stroke and provide their interpretation of findings and potential limitations of the three recently published randomized trials. The authors discuss the advantage of stent-retriever technology over earlier endovascular approaches and review the current status and future directions of endovascular acute stroke studies based on lessons learned from previous trials.

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Ongoing Improvement in Acute Ischemic Stroke Therapy Per Concurrent Guidelines and Easily Implementable Quality Improvement Protocol

Neuroscience and Neurological Surgery ◽

10.31579/2578-8868/184 ◽

2021 ◽

Vol 8 (6) ◽

pp. 01-09

Author(s):

Wengui Yu

Keyword(s):

Quality Improvement ◽

Ischemic Stroke ◽

Acute Stroke ◽

Acute Ischemic Stroke ◽

Stroke Care ◽

Linear Regression Models ◽

Stroke Therapy ◽

Acute Stroke Care ◽

Stroke Registry ◽

Intravenous Tissue Plasminogen Activator

Background: Despite proven efficacy of intravenous tissue plasminogen activator (tPA) and endovascular thrombectomy (EVT) in acute ischemic stroke, there has been slow administration of these therapies in the real world practice. We examined the ongoing quality improvement in acute stroke care at our comprehensive stroke center. Methods: Consecutive patients with acute ischemic stroke from 2013 to 2018 were studied. Patients were managed using Code Stroke algorithm per concurrent AHA guidelines and a simple quality improvement protocol implemented in 2015. Demographics and clinical data were collected from Get-With-The-Guideline-Stroke registry and electronic medical records. Patients were divided into 3 groups per admission and implementation date of quality improvement initiatives. Quality measures, including rates of intravenous tPA and EVT, door-to-needle (DTN) time, and door-to-puncture (DTP) time, were analyzed with general mean linear regression models and Jonckheere-Terpstra test. Results: Of the 1,369 eligible patients presenting within 24 hours of symptom onset or wakeup stroke, the rate of intravenous tPA was 20%, 30% and 22%, respectively, in 2013-2014, 2015-2016, and 2017-2018. In contrast, EVT rate was 9%, 14% and 15%, respectively. Based on Jonckheere-Terpstra test, there was significant ongoing improvement in the median DTN time (57, 45, 39 minutes; p < 0.001) and DTP time (172, 130, 114 minutes; p =0.009) during the 3 time periods, with DTN time ≤ 60 and ≤45 minutes in 80% and 63% patients, respectively, in 2017-2018. Conclusions: Getting with the guidelines and simple quality improvement initiatives are associated with satisfactory rates of acute stroke therapy and ongoing improvement in door to treatment times.

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Views of Emergency Physicians on Thrombolysis for Acute Ischemic Stroke

Journal of brain disease ◽

10.4137/jcnsd.s2231 ◽

2009 ◽

Vol 1 ◽

pp. JCNSD.S2231 ◽

Cited By ~ 3

Author(s):

Bentley J. Bobrow ◽

Bart M. Demaerschalk ◽

Joseph P. Wood ◽

Albert Villarin ◽

Lani Clark ◽

...

Keyword(s):

Ischemic Stroke ◽

Confidence Interval ◽

Acute Ischemic Stroke ◽

Odds Ratio ◽

Internet Survey ◽

Emergency Physicians ◽

Intravenous Tissue Plasminogen Activator ◽

Tissue Plasminogen ◽

Attitudes And Knowledge ◽

Risk Of Hemorrhage

Background The 3-hour window for treating stroke with intravenous tissue plasminogen activator (t-PA) requires well-organized, integrated efforts by emergency physicians and stroke neurologists. Objective To evaluate attitudes and knowledge of emergency physicians about intravenous t-PA for acute ischemic stroke, particularly in primary stroke centers (PSCs) with stroke neurology teams. Methods A 15-question pilot Internet survey administered by the Arizona College of Emergency Physicians. Results Between March and August 2005, 100 emergency physicians responded: 71 in Arizona and 29 in Missouri. Forty-eight percent practiced at PSCs; 48% thought t-PA was effective, 20% did not, and 32% were uncertain. PSC or non-PSC location of practice did not influence endorsement (odds ratio, 0.96; 95% confidence interval, 0.27–1.64). Of those opposing t-PA, 87% cited risk of hemorrhage. Conclusions Most emergency physicians did not endorse t-PA. Improved collaboration between emergency physicians and stroke neurologists is needed.

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Sex and Race‐Ethnic Disparities in Door‐to‐CT Time in Acute Ischemic Stroke: The Florida Stroke Registry

Journal of the American Heart Association ◽

10.1161/jaha.120.017543 ◽

2021 ◽

Author(s):

Sai P. Polineni ◽

Enmanuel J. Perez ◽

Kefeng Wang ◽

Carolina M. Gutierrez ◽

Jeffrey Walker ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Stroke ◽

Acute Ischemic Stroke ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Secondary Analysis ◽

Ethnic Disparities ◽

Stroke Registry ◽

Intravenous Tissue Plasminogen Activator ◽

Tissue Plasminogen

Background Less than 40% of acute stroke patients have computed tomography (CT) imaging performed within 25 minutes of hospital arrival. We aimed to examine the race‐ethnic and sex differences in door‐to‐CT (DTCT) ≤25 minutes in the FSR (Florida Stroke Registry). Methods and Results Data were collected from 2010 to 2018 for 63 265 patients with acute ischemic stroke from the FSR and secondary analysis was performed on 15 877 patients with intravenous tissue plasminogen activator‐treated ischemic stroke. Generalized estimating equation models were used to determine predictors of DTCT ≤25. DTCT ≤25 was achieved in 56% of cases of suspected acute stroke, improving from 36% in 2010 to 72% in 2018. Women (odds ratio [OR], 0.90; 95% CI, 0.87–0.93) and Black (OR, 0.88; CI, 0.84–0.94) patients who had strokes were less likely, and Hispanic patients more likely (OR, 1.07; CI, 1.01–1.14), to achieve DTCT ≤25. In a secondary analysis among intravenous tissue plasminogen activator‐treated patients, 81% of patients achieved DTCT ≤25. In this subgroup, women were less likely to receive DTCT ≤25 (0.85, 0.77–0.94) whereas no significant differences were observed by race or ethnicity. Conclusions In the FSR, there was considerable improvement in acute stroke care metric DTCT ≤25 in 2018 in comparison to 2010. However, sex and race‐ethnic disparities persist and require further efforts to improve performance and reduce these disparities.

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Abstract 3967: Interdisciplinary Emergency Department (ED) Acute Stroke Case Review Decreases Door to Needle (DTN) Times

Stroke ◽

10.1161/str.43.suppl_1.a3967 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Melissa T Fritz ◽

Sandy Fritzlar

Keyword(s):

Ischemic Stroke ◽

Acute Stroke ◽

Acute Ischemic Stroke ◽

The United States ◽

Case Review ◽

Intravenous Tissue Plasminogen Activator ◽

Stroke Team ◽

Process Oriented ◽

Stroke Case ◽

Iv Tpa

Background: Stroke is one of the leading causes of death and the leading cause of disability in the United States. Previous studies suggest that the quicker that intravenous tissue plasminogen activator (IV tPA) is administered, the safer and more effective it is, thus lowering the odds of in hospital mortality and symptomatic intracranial hemorrhage. Objective: To investigate whether implementing a process oriented, interdisciplinary bimonthly review of acute ischemic stroke cases would decrease DTN times and ultimately lead to the consistent administration of IV tPA within 60 minutes of arrival to the ED. Methods: To decrease the IV tPA DTN times, the stroke team at United Hospital in St. Paul, Minnesota developed a new ED stroke review process in July 2010 to analyze each acute ischemic stroke case. The cases were compiled into a document that contained time specific goals for each step of the acute stroke code process. Members of the stroke team would review the data prior to the meeting and if there was a delay (ie outside of the timed goal for lab result) in their department they would investigate the cause. At the meeting, the team would identify best practice efficiencies and barriers, leading to changes in the process. Formal follow up with each department and key learnings were sent to staff on a monthly basis. Results: In 2010, there were 82 patients admitted with an acute ischemic stroke, within 3.5 hours from time last known well, and 28 patients received IV tPA 34% (28/82). From January to June, 2011 there have been 46 acute ischemic stroke patients and 18 patients received IV tPA (18/46) 39%. The mean DTN time was 88 minutes in 2010 vs. 70 minutes in 2011; mean age was 64 vs. 66.5; % female was 46% (13/28) vs. 67% (12/18); median NIH Stroke Scale was 6 vs. 6. The percentage of patients treated with IV tPA within 60 minutes of hospital arrival increased from 21.4% (6/28) in 2010 to 50% (9/18) from January to June 2011 (p=0.022). Conclusions: The DTN times significantly decreased after the implementation of a process oriented, interdisciplinary ED acute stroke case review. The percentage of patients receiving IV tPA within 60 minutes increased from 21.4% to 50% over a 18 month period.

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Endovascular therapy in acute ischemic stroke: The way forward after results from the IMS 3, SYNTHESIS and MR Rescue trials

Indian Journal of Neurosurgery ◽

10.4103/2277-9167.118108 ◽

2013 ◽

Vol 02 (02) ◽

pp. 115-118 ◽

Cited By ~ 2

Author(s):

Bijoy Menon ◽

Mayank Goyal

Keyword(s):

Ischemic Stroke ◽

Acute Stroke ◽

Acute Ischemic Stroke ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Endovascular Therapy ◽

Current Status ◽

Intravenous Tissue Plasminogen Activator ◽

Tissue Plasminogen ◽

Iv Tpa

AbstractEndovascular therapy (EVT) has gained vogue in the management of patients with acute stroke. Newer stent-retriever devices have led to better recanalization rates. In many centers, EVT is slowly being used as an add on to or in some instances, even as an alternative to intravenous tissue plasminogen activator (IV tPA). The publication of the results of the SYNTHESIS expansion, Interventional Management of Stroke III and Mechanical Retrieval Recanalization of Stroke Clots Using Embolectomy trials in 2013 has questioned the enthusiastic use of EVT in acute stroke. They demonstrate that EVT (using a variety of devices) is no superior to IV tPA in the management of acute stroke. In the light of these controversial findings, we review the current status of EVT in the management of acute stroke.

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