International Research Led by UH Physician-Scientist Shows Endovascular Thrombectomy Benefits Patients with Large Strokes, Paradigm Shift to Support Greater Use of EVT for Improved Outcomes

UH Research & Education Update | June 2024

The incisive neurology research led by Amrou Sarraj, MD, shows patients with large ischemic strokes benefit from endovascular thrombectomy, challenging current knowledge and medical practices to improve outcomes, life expectancy, and quality of life.

Amrou Sarraj, MD

Dr. Sarraj is the Global Principal Investigator for "SELECT2: A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke." The award-winning trial established the efficacy and safety of endovascular thrombectomy in patients with large core strokes. The research, published in the New England Journal of Medicine on Apr. 6, 2023, demonstrated better clinical and functional outcomes in patients undergoing mechanical thrombectomy at the 90-day follow-up compared to those who received standard medical management only. Dr. Sarraj and the trial were recently honored by the Clinical Research Forum in Las Vegas, NV, with a 2024 Top Ten Clinical Research Achievement Award on Apr. 2, 2024 for significantly advancing clinical research.

Subsequent analysis of SELECT2 data has affirmed the benefits of thrombectomy in patients once considered too high risk to undergo the minimally invasive procedure. Earlier this year, Dr. Sarraj and his team reported that patients had a dramatically better recovery after thrombectomy plus medical management at the one-year follow-up. The findings appeared in the Feb. 9, 2024 issue of The Lancet to coincide with its presentation at the International Stroke Conference (ISC 2024) in Phoenix.

"Undoubtedly, patients with large strokes benefit from thrombectomy, which improves their functionality at three months and improves their likelihood of being independent and able to walk without assistance at one year," Dr. Sarraj says. The continued functional and quality of life improvement exceeds what would be possible with the best medical management.

SELECT2 Trial Provided a Firm Foundation for Evidence-Based Clinical Practices to Take Root

The SELECT2 trial was a groundbreaking global effort, spanning 31 comprehensive stroke centers and tertiary hospitals in the U.S., Canada, Europe, Australia, and New Zealand, with UH as the coordinating center. Conducted between September 2019 and September 2022, it comprised a total of 352 patients, ages 18-85, with large ischemic strokes. Participants were randomly assigned treatment with thrombectomy or standard medical management alone. Ultimately, patients with large strokes experienced significantly better outcomes after thrombectomy plus medical management than patients who only received only standard medical management.

Studies in Japan, China and Europe have also demonstrated outcomes similar to SELECT2, signaling a major advancement in stroke therapy worldwide by raising the potential for more hospitals to evaluate and revise their stroke guidelines to use thrombectomy more widely in severe stroke patients to improve clinical outcomes and long-term function, says Dr. Sarraj. University Hospitals is among those that have changed its protocols to extend thrombectomy eligibility to large stroke patients.

“Where does the Benefit Lie?” – Insights from SELECT2 Sub-analyses

Furthermore, a sub-analysis involving imaging examined whether the effectiveness of thrombectomy varied by the extent of ischemic injury and evidence of salvageable brain tissue on neuroimaging. According to the researchers, thrombectomy improved clinical outcomes in patients across a broad spectrum of ischemic injury, with or without advanced imaging evidence of salvageable brain tissue. However, as the extent of stroke injury increased, functional outcomes worsened. Patient age, time elapsed between imaging and procedure, and the extent of ischemic injury were prognostic factors. The research appeared online in JAMA on Feb. 7, 2024.

In another SELECT2 analysis evaluating outcomes for large core stroke patients who were transferred from referring hospitals to thrombectomy-capable medical centers, researchers found that despite longer transfer times and deterioration in neuroimaging among these patients, thrombectomy still produced better clinical outcomes in transferred patients. These findings appeared online in the Feb. 8 issue of JAMA Neurology.

A lot of patients present to hospitals without thrombectomy capabilities and then are transferred to hospitals with higher level of care for EVT considerations. However, patients with large core strokes may be excluded from transfers because of plausibly poor outcomes. SELECT2 analysis demonstrated that even those with established large core at outside hospitals demonstrated benefit of EVT. Sarraj said, “These findings open the door for large core patients presenting at outside hospitals to be transferred for EVT consideration. This will have significant impact on current stroke systems of care, which need to be rethought and reorganized to efficiently deal with increased volume and potential needs for higher level of support during transfer.”

Long-term Outcomes from SELECT2 Study Demonstrate Sustained Benefits of Thrombectomy in Treating Severe Strokes

Well-designed studies yield critical insight and drive more detailed research analysis. The primary SELECT2 study is no exception. For instance, long-term outcomes for large core stroke patients treated with thrombectomy were unknown, though they were expected to take longer to achieve optimal stroke outcomes. Analysis of long-term follow-up of SELECT2 trial indicated that patients with large strokes who undergo thrombectomy achieve statistically better functional outcomes at the one-year post-stroke follow-up compared to those who received medical care only. In fact, patients receiving thrombectomy demonstrated close to three times higher rates of independent living and twice the rates of independent walking, according to the SELECT2 one-year follow-up. Likewise, thrombectomy appeared to reduce mortality at the one-year point but not to a statistically significant degree. Notably, thrombectomy patients achieved better quality of life scores, with fewer signs of depression and cognitive decline.

“This is irrefutable evidence that patients are more likely to benefit from endovascular thrombectomy than they are likely to be harmed, and they should be treated,” says Dr. Sarraj. “Big changes on CT or perfusion scans should not deter physicians from treating these patients” because they are still likely to do better than those medically managed without thrombectomy intervention. “While the data on rehabilitation following the discharge was not available, the fact that patients continued to improve ill one year highlights the need to provide means of support, as in rehabilitation, to give these patients their best chance towards recovery".

The breadth and depth of the research Dr. Sarraj leads reframes how physicians diagnose and treat patients with large strokes, irrespective of the size of their infarction, or whether a patient is transferred from another medical facility for treatment.

Next Steps

Moving forward, Dr. Sarraj and his team will work to refine their research, evaluating patient care variables and prognostic factors to weigh the potential benefit of thrombectomy more accurately and predict long-term outcomes in large stroke patients. Of particular interest is developing a randomized trial to study the effectiveness of thrombectomy more than 24 hours after the onset of severe stroke symptoms.

A frequent presenter at national and international clinical trial plenaries, he was awarded the Mordecai Y. T. Globus New Investigator Award in Stroke in 2013 and the Stroke Care in Emergency Medicine Award in 2020 from the American Heart Association/American Stroke Association.