This engaging session, presented by Joseph McCall, MD, MBA, the division chief of the neurohospitalist division and clinical assistant professor at Thomas Jefferson University in Philadelphia, provided an overview of the past, present, and future in the world of stroke care. Globally, approximately one in six individuals will experience a stroke in their lifetime. Given that roughly 87% of strokes are ischemic, most of the session focused on ischemic strokes, from acute presentation to chronic management.1 The presentation combined foundational studies, clinical questions, and recent trials that may influence future care and guidelines.
For many attendees, the most striking study was the ZODIAC trial (zero-degree head positioning in hyperacute large artery ischemic stroke). In this study, 92 patients with a newly diagnosed large vessel occlusion, awaiting thrombectomy across 12 U.S. hospitals, were randomized to either a 0-degree or standard 30-degree head elevation group.
The primary endpoint was early neurological deterioration (END), defined as an increase of two or more points on the National Institutes of Health Stroke Scale (NIHSS). END was assessed every 10 minutes from the initiation of positioning until the start of thrombectomy or for up to two hours, whichever came first. The primary outcomes showed that only 2.2% of patients in the 0-degree group experienced END, compared to 55.3% in the 30-degree group. Surprisingly, 90-day all-cause mortality was significantly lower in the 0-degree group (4.4%) compared to the 30-degree group (21.7%). Furthermore, no cases of intracerebral hemorrhage or aspiration pneumonia were observed in the 0-degree group. The findings resonated with many attendees as the presenter shared cases in which physical exam deficits in acute stroke patients resolved when the patients were lying flat.
For thrombolysis administration, the presenter began by reviewing the landmark 1995 National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study, which was the first to establish the efficacy of thrombolysis within a three-hour time frame for ischemic stroke. Subsequently, in 2008, the ECASS-III (European Cooperative Acute Stroke Study III) broadened the window to four and a half hours from symptom onset. The significant benefit of early reperfusion for those who met criteria was graphically demonstrated in 2010.2 This showed on average, patients treated with tPA recovered two-thirds while placebo patients improved only half of the way toward full normalcy.
More recently, two studies have suggested the possibility of expanding this window further for select patients who are not candidates for thrombectomy. The TIMELESS trial (Thrombolysis in Imaging-Eligible, Late-Window Patients to Assess the Efficacy and Safety of Tenecteplase) found that, in selected patients treated between four and a half and 24 hours after symptom onset, Tenecteplase did not significantly increase the risk of intracranial hemorrhage compared to placebo. Another study, the TRACE-III trial (Tenecteplase for ischemic stroke at 4.5 to 24 hours without thrombectomy), demonstrated that 33% of patients receiving Tenecteplase achieved a modified Rankin Scale score of 0 to 1 at 90 days, compared to 24% in the standard medical therapy group. These findings cautiously suggest that, for certain patients, extending the thrombolytic window may offer benefits without significantly increasing bleeding risk. Upcoming studies are anticipated given these results and the notable disability burden in survivors of ischemic stroke who are unable to receive care within four and a half hours of symptom onset.
For reducing recurrent stroke risk in patients with minor ischemic stroke or high-risk transient ischemic attack (TIA), the class IIa American Heart Association/American Stroke Association guideline for dual antiplatelet therapy remains at 21 days, and prolonged therapy increases the risk of major bleeding without significant additional benefit. Two landmark trials shaped this recommendation: The CHANCE (Clopidogrel in High-Risk Patients with Acute and Non-Disabling Cerebrovascular Events) trial and the POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial.
The ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke) trial, published in 2024, examined whether apixaban reduces the risk of recurrent stroke compared to low-dose aspirin in patients with cryptogenic ischemic stroke and evidence of atrial cardiopathy, but without atrial fibrillation. The randomized controlled trial, which included approximately 1,000 patients, showed no significant difference as both groups had an annual recurrent stroke rate of approximately 4.4%.
Clinical questions during the session reinforced key points, such as avoiding routine repeat imaging in stable ischemic stroke patients unless there is neurological deterioration. Additionally, the importance of ruling out hypoglycemia in patients presenting with stroke-like symptoms was highlighted, along with maintaining target glucose levels of 140 to 180 mg/dL in patients with confirmed ischemic stroke.
Dr. Singh is an associate professor at the University of New Mexico-Sandoval Regional Medical Center in Rio Rancho, N.M., and currently serves as the past president for SHM’s New Mexico chapter.
References
- Feigin VL, et al. Global burden of stroke. Circ Res. 2017;120(3):439-448. doi:10.1161/CIRCRESAHA.116.308413.
- Saver JL, et al. Graphic reanalysis of the two NINDS-tPA trials confirms substantial treatment benefit. Stroke. 2010;41(10): 2381-2390. doi: 10.1161/STROKEAHA.110.583807