In the US, a person suffers from stroke every 40 seconds, while someone dies from stroke every 4 minutes.1 As one of the leading causes of disability nationally, stroke is an evergreen field for research regarding care and treatment of this patient demographic.
According to researchers from a recent CERENOVUS study, first-pass effect is an independent predictor of good functional outcomes in the endovascular treatment of acute ischemic stroke. Findings also indicated that mechanical thrombectomy significantly lessens health care spending during the first year following ischemic stroke when complete or near complete reperfusion is achieved at the first pass, compared with when achieved at more than 1 attempt.2
We spoke with Dr Tom Yao, a neurosurgeon affiliated with Norton Health and consultant at Johnson & Johnson Pharmaceuticals, to discuss the future and challenges of stroke research, first-pass effect, and findings from the recent CERENOVUS study.
What do you believe is the future of stroke research in the upcoming 5 years?
There are many aspects of stroke research that have the potential to improve patient outcomes; however, mechanical thrombectomy (MT) — a minimally invasive procedure — is a high-impact part of stroke care that could have immediate impact on good patient outcomes. The goal of stroke treatment is preventing brain cells from dying, because once brain cells die, they do not regenerate — leading to disability and death.
Stroke is still a leading cause of disability and death in the [US].1 However, over the past decade, advancements in MT have improved the safety, success, and efficacy of MT, which has decreased the overall death and disability for those who suffer from strokes.3 Recent randomized clinical trials have even transformed MT into first-line stroke treatment. In short, the faster the blockage is removed from the brain during a stroke, the more brain cells can be saved, leading to a better clinical outcome.
We can impact patients’ and families’ quality of life by limiting neuronal death. We can do this by affecting time to complete restoration of blood flow, which can be done in many ways. Stroke research should focus on innovation of devices and catheter access devices.
Improving speed, success, and efficacy of revascularization in the shortest amount of time lead to a significantly improved patient outcome (both quality and quantity of life).4 Each generation of devices has led to the conclusion known as the first-pass effect (FPE). Yet, even with the success of MT has brought to the stroke world, patient outcomes can always be better.
Together with MT we need improved community awareness and education. These aspects are often overlooked in [favor of] increasing the speed of treatment and access to comprehensive stroke care. Improved symptom recognition for patients would lead directly to decreased time to receiving definitive treatment. Knowing that there are specialized hospital systems that are certified Comprehensive Stroke Centers (CSC) would decrease the need for patient transfers from centers that do not offer the complete spectrum of care that CSC offer, as these transfers directly delay definitive care for many stroke patients.
Continuing to streamline the process from the field evaluation to the correct hospital will improve the clinical outcomes, because time is brain — and the sooner a stroke is recognized and treated, the better the clinical outcome. By focusing on and investing in research with this multi-pronged approach, we can help to prevent deaths, improve the overall outcome of patients that suffer from strokes, and improve the quality of life for survivors.
Can you explain the importance of the first-pass effect (FPE) and results from the recent CERENOVUS study? What are the clinical implications of these findings?
[FPE] describes patients who underwent MT and showed improved outcomes with single pass at restoring blood flow to the brain, compared to those that require multiple pass attempts.
Repeated thrombectomy passes may be associated with an increased risk of vessel injury and an increased time to restoration of blood flow, which can potentially impact clinical outcomes. Due to this, FPE should be the procedural goal in the endovascular treatment of acute ischemic stroke, as it demonstrates the most favorable patient outcomes, as well as positively impacts health care spending. Therefore, increased research on device efficacy and delivery would help us achieve FPE more frequently.
The recent CERENOVUS study published in the Journal of NeuroInterventional Surgery highlights the patient and economic benefits of achieving FPE during mechanical thrombectomy.5 Specific results include:
- Reduced risk of vessel injury and irritation, lower rate of complication, and shortened procedure time
- Significantly earlier hospital discharge, with length of stay reduced from 9.48 days to 6.10 days
- Potential per-patient cost savings of up to $6,575 during the acute care phase in the hospital
Beyond hospitalization, additional cost savings are projected in the first year after stroke at around $4,116.
What areas of stroke research remain in need of attention? Why is continued innovation in these areas important?
Continued research and innovation into the devices that are being used and how they are delivered, patient and community education, and health care infrastructure are critically important to help patients and improve outcomes. Streamlining and developing improvements in these areas will directly lead to new technologies and procedures that physicians can use in practice to help our stroke patients.
Effectiveness, safety, and the ability to deliver devices should continue to be a main focus of stroke research. This will allow us to improve the time to complete blood flow restoration without causing unwanted injury. For example, continued innovation and research into FPE will help us better understand FPE predictors, as well as how we can make more effective use of this marker for success in stroke treatment.
The other aspect of stroke which requires continued support is getting the patient to the hospital sooner. This involves community awareness, as well as community infrastructure. Our communities need to understand that there are only certain hospitals or comprehensive stroke centers certified to handle all aspects of stroke care and the complexity of neurovascular care.
Many people outside of healthcare aren’t aware that not all hospitals offer a complete complement of stroke care professionals. CSCs are centers that offer:
- Availability of advanced imaging techniques, including MRI/MRA, CTA, DSA, and TCD
- Availability of personnel trained in vascular neurology, neurosurgery, and endovascular procedures
- 24/7 availability of personnel, imaging, operating room, and endovascular facilities
- ICU/neuroscience ICU facilities and capabilities
- Experience and expertise treating patients with large ischemic strokes, intracerebral hemorrhage and subarachnoid hemorrhage including research contributions
What challenges have there been in this field of research, and how have they been addressed?
The treatment of stroke has exponentially improved over the past 10 to 15 years. In fact, 10 years ago, we were still trying to figure out which devices would be safe for deployment in the brain. We would spend hours trying to get a vessel open, and 50% of the time we were unsuccessful.
Today, it is a far cry from when we were first performing MT. We used to say “if we could get the vessel open.” As catheters and devices have improved, we now can say “when we get the vessel open.”
Research now needs to focus on:
- How we can get the patient to the right hospital (CSC) faster (community awareness of both the disease process and hospitals that can treat)
- How surgeons can perform the surgery more quickly, effectively, and safely (improvements in catheters, approaches, and devices).
How has the COVID-19 pandemic impacted this direction in research?
COVID-19 has captured the attention of the world and impacted the progress of other health initiatives. For instance, many laboratory values and tests have been limited because there were not enough materials to perform them, and these shortages often directly affect patient care. Additionally, several research studies had to halt or slow down because we are unable to continue enrollment in studies, secondary to limitations of meeting in person.
Now that there is a better understanding of this virus and widespread vaccination efforts are in place, we must begin to push forward with other initiatives and refocus on areas like stroke care.
Do you have anything else you would like to add regarding R&D therapy, the direction of stroke research, or the implications thereof given the ongoing pandemic?
As an industry, we need to keep striving to do what is best for the patient. If we continue to advocate for patient care, the necessary improvements in research and development will have a positive impact on their treatments.
1. “Stroke Facts.” The Centers for Disease Control and Prevention. March 2021. www.cdc.gov/stroke/facts.htm
2. Zaidat OO, Ribo M, Mattle HP, et al. Health economic impact of first-pass success among patients with acute ischemic stroke treated with mechanical thrombectomy: a United States and European perspective. J Neurointerv Surg. Published online December 21, 2020. doi:10.1136/neurintsurg-2020-016930
3. McCarthy, David J, et al. Long-term outcomes of mechanical thrombectomy for stroke: a meta-analysis. ScientificWorldJournal. Published online May 2, 2019. doi:www.ncbi.nlm.nih.gov/pmc/articles/PMC6521543/
4. Zaidat OO, Castonguay AC, Lifante I, et al. first pass effect. a new measure for stroke thrombectomy devices. Stroke. 2018;49(3):660-666. doi:10.1161/STROKEAHA.117.020315
5. New CERENOVUS study demonstrates cost-savings associated with first-pass effect in mechanical thrombectomy for treating acute ischemic stroke in the US and Europe. Irvine, CA: Johnson & Johnson. January 11, 2021. Accessed May 13, 2021.