Ischemic Stroke Patient Case Study

Introduction

We have not yet completed clinical hours for primary care so I am using a compilation of examples from work. I currently work in the emergency department in Minot, ND and we often care for ischemic stroke patients. Determining when the stroke symptoms began is one of the most important and most challenging questions to answer. Some patients wake up with stroke symptoms, some have a witnessed incident, and some are found after an unknown amount of time. Depending on the timetable, and whether or not patients meet criteria determines whether the patient will be treated with intravenous tPA or mechanical removal of the clot or tPA placed specifically on the clot via intra-arterial access. I decided to compare mechanical removal with

intravenous tPA to determine which method produced better patient outcomes.
My literature search involved Google, Google Scholar, and Welder Library eResource Cochrane. I used a variation of key words including: “tPA vs. mechanical clot removal,” “efficacy of mechanical clot removal in ischemic stroke,” “efficacy of tPA in ischemic stroke” “ischemic stroke treatment,” and “tissue plasminogen activator.” I found only a handful of studies that pertained specifically to my research topic. Many of the articles I found dealt with specific patient groups but I wanted a broad range of ischemic stroke patients included in the study. The three studies I will present in this paper best represent the efficacy of tPA as well as the efficacy of mechanical removal of the blood clot. These studies compare multiple studies and have some crossover comparisons with each other.
PICO question: For ischemic stroke patients, does medication treatment with tissue plasminogen activator offer improved quality of life compared to mechanical treatment to physically remove the clot?
Annotated Bib
del Zoppo, G., Saver, J., Jauch, E., & Adams, H. (2009). Expansion of the Time Window
for Treatment of Acute Ischemic Stroke With Intravenous Tissue
Plasminogen Activator. AHA/ASA Science Advisory (40), 2945-2948.

I believe this article is a level 7, opinion of authorities and expert committees according to the Pyramid of Evidence provided in the syllabus of this course. This evidence guideline regarding the time in which tPA treatment must be initiated is provided by staff members of the American Heart Association/American Stroke Association.
This article compiled results from the ECASS-3, SITS-MOST, and SITS-ISTR studies/research centers regarding outcomes of ischemic stroke patients treated with intravenous tPA within 4.5 hours from onset of symptoms during a five year time period. This compilation of research focused on approximately 13,350 patients who were treated with tPA within 3 hours, treated with tPA between 3 and 4.5 hours, and treated with a placebo. All of these patients were under the age of 80, were not taking anticoagulant medications, had an NIHSS score less than or equal to 25, and did not have a history of stroke and diabetes.
The population characteristics were appropriate because they follow the American Stroke Association guidelines for treatment with tPA. Using patients from both the United States and Europe increases the validity of this study because it makes the results more globally accurate. The fact that over 13,000 people were studied and placebos were used also increases the validity and reproducibility of the results. The main weakness in the internal validity of this study is minimal time for follow-up after treatment. The subjects of this study were only followed for 90 days after treatment, which is sufficient enough for the purpose of the study but doesn’t provide enough information for long-term prognosis, such as recurrent stroke or subsequent hemorrhagic stroke. The external validity is supported by the size of the subject pool but weakened by the narrow population characteristics.
This research article is current because it was written within the last ten years and newer research does not dispute the findings. The relevancy perfectly fits the PICO question mentioned at the beginning of this paper. The authority, accuracy and purpose of this article are validated because it was written and published by the AHA/ASA who are the leading research and guideline associations for cardiovascular disease and stroke. This study is limited by the population characteristics and time frame of follow up. This article found that the use of tPA on eligible ischemic stroke patients within 4.5 hours from onset of symptoms provided a decrease in morbidity and mortality as well as increased quality of life.
Annotated Bib
Lansberg, M., Bluhmki, E., & Thijs, V. (2009). Efficacy and Safety of Tissue
Plasminogen Activator 3 to 4.5 Hours After Acute Ischemic Stroke. Journal of
the American Heart Association (40), 2438-2441.

I believe this article is a level 1, systematic review of multiple random controlled trials according to the Pyramid of Evidence provided in the syllabus of this course. This metaanalysis provides evidence and results from several studies done on Europe and the U.S.
This article compiled and compared results from the ECASS-1, ECASS-2, ECASS-3 and ATLANTIS studies. Approximately 1,622 subjects were studied. These patients were treated with tPA within 3-4.5 hours from onset of symptoms. These subjects were followed for 90 days after initial treatment. All four randomized control trials showed increased quality of life for these patients.
This study, like the previously discussed article, followed the AHA/ASA guidelines for eligibility of tPA treatment. This means that all patients in the study were younger than 80, were not taking anticoagulant medications, had an NIHSS score less than or equal to 25, and did not have a history of stroke and diabetes. The results are validated because each of the four studies has significantly similar results. One weakness for internal validity is the difference of doses for tPA used. One study used a does of 1.1mg/kg whereas the other three used the standard 0.9mg/kg dose of tPA. Another internal validity weakness is the small sample size. The previously discussed study involved over 13,000; whereas this study only contained 1,622, which is approximately 12% of the previous article subjects. External validity is narrowed because, once again, the population characteristics are narrowed by the AHA/ASA guidelines for eligibility.
This study is current because it was conducted within the last ten years without being disputed by newer research. The relevancy is proven because the article provides information directly involving the PICO question. The article was written and published by the AHA/ASA who are the utmost respected authorities for stroke research and guidelines. The accuracy and purpose of the article are clearly stated in the introduction and discussion sections. The research is limited by the small sample size, the narrowed population characteristics due to national guidelines, and the short follow up period. This meta-analysis determined advantageous outcomes with the use of tPA in patients meeting the national guideline criteria within 4.5 hours from onset of symptoms.
Annotated Bib
Smith, W., Sung, G., Starkman, S., Saver, J., Kidwell, C., Gobin, P., et al. (2005). Safety
and Efficacy of Mechanical Embolectomy in Acute Ischemic Stroke. Journal of
the American Heart Association (36), 1432-1438.

I believe this article is a level 2, single random controlled trial according to the Pyramid of Evidence provided in the syllabus of this course. This article is an evidence summary from the MERCI trial.
Unlike the two previously discussed articles, this research involves the use of mechanical removal of the clot in ischemic stroke patients. These patients are outside of the previously mentioned guidelines. The subjects of the MERCI study were over the age of 80, possibly taking anticoagulant medications, has an NIHSS score of 25 or higher, and beyond the 4.5 hour window from onset of stroke symptoms. The procedure was not performed beyond eight hours after onset of symptoms because previous research showed decline in patient outcome past eight hours. This study was conducted using 151 patients from 25 stroke centers in the U.S. No more than six passes with the device were allowed in order to be deemed successful. The study was conducted over an 18-month period.
The results of the study are partially valid because they can likely be reproduced using a similar sized sample with the same guidelines. The internal validity is challenged by the size of the subject population. The other two studies discussed used far more patients, which makes them stronger. The small sample size in this study calls for further research with a larger group. On the contrary, the external validity is stronger because it allowed a wider guideline for eligibility. I believe the sample size was smaller because fewer ischemic stroke patients meet the criteria for mechanical clot removal compared to treatment using tPA.
Although this study would be more reliable if it were more current, I could not find newer research that gave conflicting results. The authority level of this article is increased because it was published by the AHA/ASA but is still at a lower level of authority than the two previously discussed articles because AHA/ASA staff members did not write it. The accuracy and purpose are acceptable because the theme of the study specifically pertains to the PICO questions of this paper. Limitations of the study include small sample size and narrow population characteristics. I believe that further research should be done to see if mechanical removal of the blood clot on patients meeting tPA eligibility guidelines provides similar quality of life outcomes for patients.
Summarization of Findings
The studies outlined above show the efficacy and positive prognosis of tPA treatment for eligible patients within the 4.5 hour window after stroke symptoms begin as well as the efficacy and positive prognosis of those not eligible for tPA through mechanical removal of the clot. Both methods of treatment had similar results, showing between 45% and 66% of patients having significant improvement, despite the severe difference in patient acuity levels. Mechanical removal of blood clot is only performed on patient who are outside the 4.5 hour timeframe, over the age of 80, taking anticoagulants, or the stroke is too severe for tPA treatment; and yet the outcome results for patients were nearly identical for younger patients, not taking anticoagulants, within the 4.5 hour window treatment with intravenous tPA. I think this means it is possible for mechanical removal of blood clots on patients meeting requirements for intravenous tPA to have better outcomes than those who are treated with tPA. This is just a guess at this point because the research to prove it does not exist.
Application
I believe that more research needs to be done to actually compare intravenous tPA with mechanical removal of the clot.

These methods have been thoroughly researched on their own but a comparison study with similar patient populations would be the best way to show which method has better patient outcomes. The studies reviewed in this paper used patients of different acuity but had similar results. I think this means mechanical removal of the clot could be more efficacious that intravenous tPA in lower acuity stroke patients. I could not find research on this specific subject for comparison. I don’t often see patients past the point of initial treatment; therefore I don’t know the outcomes. I have seen many patients undergo each type of treatment for ischemic stroke, some begin to show improvement within the first hour of beginning tPA treatment in the ER. Without more research, I will continue to follow the AHA/ASA guidelines for tPA treatment in my clinical practice.

References

del Zoppo, G., Saver, J., Jauch, E., & Adams, H. (2009). Expansion of the Time Window

for Treatment of Acute Ischemic Stroke With Intravenous Tissue

Plasminogen Activator. AHA/ASA Science Advisory (40), 2945-2948.

Lansberg, M., Bluhmki, E., & Thijs, V. (2009). Efficacy and Safety of Tissue

Plasminogen Activator 3 to 4.5 Hours After Acute Ischemic Stroke. Journal of

the American Heart Association (40), 2438-2441.

Smith, W., Sung, G., Starkman, S., Saver, J., Kidwell, C., Gobin, P., et al. (2005). Safety

and Efficacy of Mechanical Embolectomy in Acute Ischemic Stroke. Journal of

the American Heart Association (36),

1432-1438.