On the basis of findings from the SELECT2 Clinical Trial, for which Penn Medicine was a top-enrolling study site, the Penn Comprehensive Stroke Center is now performing endovascular thrombectomy for acute ischemic stroke (AIS) in patients with large regions of early injury up to 24 hours after stroke onset.
Figure 1: CTA demonstrating open vessels on the patient's left and occlusion of the middle cerebral artery on the right.
In the setting of acute ischemic stroke, the infarct core is the territory that is generally believed to be irreversibly injured. Trials prior to SELECT2 excluded patients with large infarct cores because they were thought to be beyond the point of recovery. Further, patients with large cores were expected to be at greater risk of harm from cerebral hemorrhage and edema if treated with mechanical thrombectomy.
SELECT2 (Randomized Controlled Trial to Optimize Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke), a phase 3 international, randomized, open-label clinical trial, was led at Penn Medicine by Scott Kasner, MD, chief, division of Vascular Neurology at Penn Neurology.  SELECT2 randomly assigned patients to receive thrombectomy plus medical care, versus medical care alone. The study’s primary outcome was a modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability).
Eligible candidates included individuals with acute ischemic stroke due to occlusion of the internal carotid artery (either cervical or intracranial) or the M1 segment (main trunk) of the middle cerebral artery or both. Candidates also had a large ischemic core on noncontrast CT (defined as an ASPECTS value of 3 to 5), or an estimated ischemic-core volume of 50 ml or greater on CT perfusion imaging. ASPECTS (the Alberta Stroke Program Early CT Score) is a system used to estimate the volume of infarcted tissue. Scores range from 0 to 10, with lower scores indicating a larger area.
The final selected population assigned 178 patients to the thrombectomy group and 174 to the medical-care group. A total of 85% of enrolled patients had an ASPECTS value of 5 or less; 87% had an ischemic-core volume of 50 ml or greater; 78% of patients had a large stroke according to both measures.
SELECT2 was stopped early for overwhelming efficacy having achieved the study’s primary outcome following a shift in the distribution of modified Rankin scale scores toward better outcomes with thrombectomy. The odds of a more favorable outcome were 1.51-fold higher in the endovascular thrombectomy plus medical care population than medical care alone.
Functional independence was achieved in 20% of patients in the thrombectomy group and 7% in the medical-care group at 90 days. Further, 38% of those treated with thrombectomy could walk without assistance or supervision compared to 19% in the medical-care group. Intracranial hemorrhage was infrequent in both groups, but patients having thrombectomy saw a greater incidence of vascular injury and access-site complications. Mortality was similar in both groups.
Conclusions for Patients at Penn Medicine
As a prominent study site for SELECT2, and with demonstrated evidence of the benefits of its findings, Penn Medicine immediately expanded access to thrombectomy plus standard medical care for the vast majority of patients with stroke due to large vessel occlusion who present within 24 hours of the time they were last known to be well, including those with the full range of infarct sizes.
Of note, patients who came to Penn Medicine were able to benefit from treatment within the SELECT2 trial as early as its initiation in 2019, evidencing an institutional commitment to offer new treatment strategies through voluntary participation in stroke studies years before they are incorporated into standard care.
Penn Medicine currently offers thrombectomy for stroke at the Hospital of the University of Pennsylvania and at Lancaster General Hospital. More information about acute stroke research at the Penn Comprehensive Stroke Center is available at clinicaltrials.gov.
Mrs. L, a 64-year-old female, was found on the kitchen floor of her house by her husband after he rose to go to work. When it became clear that she couldn’t get up, Mr. L called 911. He reported to the EMS that Mrs. L worked nights, and he could only say she seemed well the previous evening.
Figure 2: CT perfusion of the core (presumed to be permanently injured area) on the left in pink, measuring 90 mL, and the penumbra (the territory expected to die if blood flow is not restored) on the right in green, 354 mL.
Mrs. L was evaluated by Drs. Donna George and Sahily Reyes-Esteves at the Penn Comprehensive Stroke Center. There, her examination was notable for right gaze preference, slurred speech, and left-sided hemiparesis, yielding an NIH stroke scale score of 12. A CT of the brain revealed an ASPECTS value of 7 with subtle hypodensity in the right hemisphere. CT angiography (CTA) demonstrated occlusion of the distal M1 branch of the right middle cerebral artery and mild atherosclerotic disease involving the carotid (Figure 1). CT perfusion demonstrated a large infarct core of 90 mL as well as a large perfusion mismatch indicating salvageable territory (Figure 2).
In the angiography suite at the Penn Comprehensive Stroke Center, Mrs. L underwent mechanical thrombectomy by neurosurgeon Dr. Jan-Karl Burkhardt using an aspiration catheter. A post-thrombectomy angiogram of the right middle cerebral artery (Figure 3) demonstrated recanalization and near complete reperfusion (TICI 2C).
Following her procedure, Mrs. L was transferred to the intensive care unit under the care of Dr. Monisha Kumar. Despite the large size of her stroke, she showed early improvement in her functional status with mild left-sided weakness. She quickly regained the ability to walk with a cane and was discharged to acute inpatient rehabilitation for about two weeks.
Figure 3: Post-thrombectomy angiogram demonstrating recanalization and near complete reperfusion of the right middle cerebral artery.
Over the next few months, she continued to improve and became independent in her activities with the exception of the inability to drive due to visual processing impairment.
About the Penn Comprehensive Stroke Center
The Joint Commission-certified Penn Comprehensive Stroke Center offers patients access to the most advanced resources available for the treatment of stroke. In addition to participating in stroke research, the Comprehensive Stroke Center offers dedicated neuro-intensive care unit beds for complex stroke patients 24/7; care for patients with diagnosed subarachnoid hemorrhage, acute ischemic stroke or aneurysm; advanced imaging capabilities and techniques; and management of post-hospital care. The Stroke Center faculty includes highly skilled vascular neurologists, neurosurgeons and neuroradiologists, who are supported in their efforts by the dedicated teams from PennSTAR, the intensive care units and the neuro-rehabilitation program.
- Sarraj A, Hassan AE, Abraham MG, Ortega-Gutierrez S, Kasner SE, Hussain MS, Chen M, Blackburn S, Sitton CW, Churilov L, Sundararajan S, Hu YC, et al, for the SELECT2 Investigators. Trial of Endovascular Thrombectomy for Large Ischemic Strokes. N Engl J Med 2023;388:1259-1271.