ISC 2026 Data Showcase New Horizons for Stroke Prevention, Recovery

The 2026 International Stroke Conference (ISC), held February 4-6 in New Orleans, Louisiana, delivered potentially practice-shifting clinical trial results that could reshape approaches to both acute stroke management and secondary prevention.

The meeting's overarching themes centered on novel pharmacologic agents for preventing recurrent events, a renewed focus on neuroprotection strategies, and optimization of recovery following mechanical interventions.

Secondary Prevention Enters New Era With Factor XIa Inhibition

The OCEANIC-STROKE trial (NCT05686070) was arguably the most anticipated presentation of the conference, introducing a fundamentally different approach to anticoagulation in stroke prevention.

The phase 3 trial evaluated asundexian, a factor XIa (FXIa) inhibitor, for recurrent stroke prevention in patients with noncardioembolic ischemic stroke or high-risk transient ischemic attack (TIA).¹ Results demonstrated a 26% relative risk reduction in recurrent ischemic stroke compared with standard antiplatelet therapy. Notably, this benefit was achieved without the increased bleeding risk traditionally associated with anticoagulation; no significant difference in major bleeding events was observed between treatment arms.

“Asundexian holds the potential to reduce the risk of a recurrent stroke over the long term without an increased safety risk. This is a major advance in our ability to prevent strokes in people at risk of stroke recurrence,” principal OCEANIC-STROKE investigator Mike Sharma, MD, MSc, the Michael G. DeGroote Chair in Stroke Prevention and professor of medicine at McMaster University in Ontario, Canada, said in a statement.²

Postthrombectomy Care Refinement

Two significant trials addressed the critical question of how to optimize outcomes after successful mechanical thrombectomy, the standard intervention for large-vessel occlusion strokes.

The CHOICE2 trial (NCT05797792) investigated adjunctive intra-arterial alteplase administration following successful recanalization.³ Patients receiving the direct cerebral delivery of thrombolytic therapy showed significantly improved functional outcomes at 90 days compared with thrombectomy alone. Investigators hypothesized that treating residual microthrombi in distal vessels—beyond what mechanical devices can reach—may be important for maximizing tissue salvage and functional recovery.

Meanwhile, late-breaking and concurrently published ESCAPE-MeVO trial (NCT05151172) data on endovascular thrombectomy for medium vessel occlusions (MeVO) showed no improvement in clinical outcomes along with higher serious adverse event rates.⁴ However, another late-breaking trial conducted in patients with moderate to severe medium-sized artery occlusions showed improved functional independent scores.⁵

Neuroprotection Makes a Comeback

After decades of stagnant progress in neuroprotection trials, ISC 2026 showcased renewed interest in this area.

The phase 3 LAIS trial (NCT06517173) evaluated loberamisal, a new neuroprotective agent, in patients with acute ischemic stroke. When initiated within 48 hours of symptom onset, loberamisal produced a 13% absolute increase in the proportion of patients achieving excellent functional outcomes (defined as modified Rankin Scale 0-1) at 90 days.⁶

Hemorrhagic Stroke Management Advances

Intracerebral hemorrhage management also saw important developments, though with mixed results.

The FASTEST trial (NCT03496883), which had overall neutral results, tested ultra-early recombinant factor VIIa administration (within 2 hours) for spontaneous intracerebral hemorrhage. Subgroup analyses found that while the intervention successfully limited hematoma expansion, this radiographic benefit did not translate into improved functional outcomes.⁷ Additionally, a small but statistically significant increase in arterial thromboembolic complications was observed, raising questions about the risk-benefit profile in routine practice.

More encouraging results came from the EMBOLISE trial (NCT04402632), which evaluated middle meningeal artery embolization for chronic subdural hematoma. This minimally invasive endovascular procedure demonstrated superiority over medical observation alone, significantly reducing the need for subsequent surgical intervention.⁸ The findings support broader adoption of this technique for a condition that frequently affects older patients on anticoagulation.

Looking Ahead After ISC 2026

The 2025 ISC annual meeting delivered on multiple fronts, offering both immediate practice implications and promising avenues for future investigation. As factor XIa inhibition moves toward regulatory review, neuroprotection is reconsidered, and intervention strategies potentially expanding to smaller vessels, the stroke care landscape appears poised for continued evolution.

References

1. McNulty R. Asundexian reduces risk of stroke recurrence in phase 3 OCEANIC-STROKE trial. AJMC^®. February 5, 2026. Accessed February 12, 2026. https://www.ajmc.com/view/asundexian-reduces-risk-of-stroke-recurrence-in-phase-3-oceanic-stroke-trial

2. New medication may reduce chances of a second clot-caused stroke without bleeding risk. News release. American Stroke Association. February 5, 2026. Accessed February 12, 2026. https://newsroom.heart.org/news/new-medication-may-reduce-chances-of-a-second-clot-caused-stroke-without-bleeding-risk

3. McNulty R. Intraarterial alteplase after thrombectomy may improve stroke recovery: CHOICE2. AJMC. February 4, 2026. Accessed February 12, 2026. https://www.ajmc.com/view/intraarterial-alteplase-after-thrombectomy-may-improve-stroke-recovery-choice2

4. Goyal M, Ospel JM, Ganesh A, et al. Endovascular treatment of stroke due to medium-vessel occlusion. N Engl J Med. 2025;392(14):1385-1395. doi:10.1056/NEJMoa2411668

5. #ISC26 Closing Main Event reports on SPAN2, I-ACQUIRE, LAIS, LUMOSA, CONCERN, MeVO, DISTALS and BCI-REHAB trials. International Stroke Conference Coverage. February 9, 2026. Accessed February 12, 2026. https://isc.hub.heart.org/daily-coverage/article/22960319/latebreaking-science-reports-on-potential-cerebroprotective-interventions-and-more

6. Started within 48 hours of stroke, neuroprotective medication helped brain cells, recovery. News release. American Stroke Association. February 6, 2026. Accessed February 12, 2026. https://newsroom.heart.org/news/started-within-48-hours-of-stroke-neuroprotective-medication-helped-brain-cells-recovery 

7. CHOICE-2, FASTEST and CREST 2 results revealed during Opening Main Event. International Stroke Conference Coverage. February 5, 2026. Accessed February 12, 2026. https://isc.hub.heart.org/daily-coverage/article/22960059/choice2-fastest-and-crest-2-results-revealed-during-opening-main-event

8. Knopman J, Davies JM, Harbaugh RE, et al. The EMBOLISE study: embolization of the middle meningeal artery with Onyx Liquid Embolic System in the treatment of subacute and chronic subdural hematoma. Presented at: International Stroke Conference; February 7-9, 2024; Phoenix, AZ. LB28