The 2026 International Stroke Conference was full of energy on the eve of Mardi Gras in the host city of New Orleans.   This year’s meeting brought brand new acute stroke management guidelines, “fireside” chats, and several high impact positive clinical trials.

Early Management of Acute Ischemic Stroke Guidelines 2026

There are about 40 new statements included in this update to the guidelines.  The scope of the guideline expanded to include Pediatric Stroke for the first time, including guidance regarding treatment of children age 28 days and over with tPA, and consideration of mechanical thrombectomy for children age 6 and older.  There is also a revision to contraindications to thrombolytics, as well as extension of the thrombolytic window using MRI DWI-FLAIR mismatch (per WAKE-UP) or perfusion mismatch (per EXTEND, TRACE-III, EPTHET, others).  There is also a new recommendation for EVT in basilar artery occlusion patients presenting within 24 hours with NIHSS ³10.  There are many more statements to review in the full publication available on the Stroke Journal website.

CHOICE2 (CHemical OptImization of Cerebral Embolectomy 2)

CHOICE2 was a larger follow up study to CHOICE1, which was terminated early during the COVID-19 pandemic.  The purpose of the trial was to further evaluate the effect of intra-arterial thrombolysis for patients after successful reperfusion of LVO with mechanical thrombectomy.  Patients were included if they had LVO with eTICI 2b-3 post MT, 4.5 to 24 hours from onset, age ³18, ASPECTS ³ 6.  Notable exclusion criteria included NIHSS ³ 25 or contraindications to tPA.  A total of 440 patients were randomized to thrombectomy with IA alteplase (0.225mg/kg, max 20mg, over 15 mins) vs thrombectomy alone.  Median NIHSS score was 15 for both groups with predominantly cardioembolic stroke etiology (50% vs 48%).  For the primary outcome measure, the treatment group had statistically significant increase in mRS 0 to 1 at 90 days (57.5 vs 42.9%) with an adjusted risk difference of 15% (P=0.002) and NNT of 7 patients.  The safety outcome data should be taken into consideration, as sICH at 36±24h was not significant (1.4% vs 0.5%) but the mortality rate was significantly higher in the treatment arm (12.1% vs 6.4%, P=0.04).  CHOICE2 adds to prior evidence from ANGEL-TNK and PEARL trials with similar results.

OCEANIC-STROKE (Oral faCtor Eleven A iNhibitor asundexian as novel antithrombotiC)

Asundexian is an investigational novel factor XI (Xia) inhibitor, which works upstream in the extrinsic coagulation cascade relative to NOACs.  This study investigated whether adding Asundexian to antiplatelet (SAPT or DAPT) therapy can prevent recurrent stroke after non-cardioembolic stroke or high-risk TIA.  Inclusion criteria were adult patients within 72 hours of mild to moderate ischemic stroke (NIHSS £ 15) or high-risk TIA (ABCD2 6 or 7). This international study randomized 12,327 patients to receive Asundexian plus anti-platelet, vs placebo plus anti-platelet.  Results demonstrate a significant reduction in recurrent ischemic stroke incidence (HR 0.74, P<0.001), as well as reduction in all strokes (P<0.001) and in the combined outcome of CV death, MI, or stroke (P<0.001).  There was no increase in ISTH major bleeding in the treatment vs control groups (1.9% vs 1.7%).  This was met with a standing ovation during the Main Event; it remains to be seen how this translates into our routine practice.

OPTION

OPTION was a trial conducted in China to evaluate the efficacy and safety of IV TNK in patients who are not thrombectomy candidates (no LVO target) presenting within 4.5-24 hrs from last known well time, with evidence of penumbra based on perfusion imaging.  They randomized 570 patients prospectively in an open-label, blinded endpoint (PROBE) trial.  Patients were included with mRS 0-1, NIHSS 4-5 with disabling deficits or NIHSS 6-25, with CT perfusion criteria of core (rCBF<30%) <50 mL, mismatch ratio ³1.2, and mismatch volume ³10 mL.  Patients with occlusion of ICA, MCA-M1, vertebral artery, or basilar artery were excluded.  For the primary outcome of mRS 0-1 at 90 days, they were able to show a significant benefit to TNK over standard medical treatment, with an unadjusted risk ratio of 1.28 (P=0.02).  Extended window TNK also appeared to be safe with no change in systemic bleeding or death within 90 days, however a small increase in sICH within 36 hrs (2.8 vs 0%, P=0.004).  The results of this trial were published concurrently with the meeting in JAMA.

The Effect of Treatment on Cognitive Function in Patients with Asymptomatic Carotid Artery Stenosis: The CREST-2 Trial

The primary results of the CREST-2 trial were previously published last year.  This secondary analysis was specifically to evaluate whether cognition was improved after revascularization.  Previous studies with smaller sample sizes have demonstrated mixed results.  The investigators utilized a telephone battery of tests with multiple domains.  When comparing CAS or CEA to medical management, there was no difference in cognitive outcomes up to and at 4 years post procedure.

FASTEST

FASTEST is a randomized, double blind, controlled efficacy trial of rFVII vs placebo in addition to best standard therapy for patients with spontaneous ICH.  Inclusion criteria are ICH volume 2-59cc, no or small IVH, and treated within 120 minutes of onset.  Initial results did not show a significant change in mRS at 180 days in by intention-to-treat or per-protocol analyses.  Secondary outcome did demonstrate reduced growth of ICH and ICH plus IVH volumes, however with increased rate of life-threatening thromboembolic complication (p=0.02).  The investigators reported trend toward improved mRS in the intervention group <90 mins from onset or with CT spot sign within 120 mins from onset, and thus plan to continue enrollment with modified inclusion criteria as “FASTEST part 2”.

EMBOLISE

EMBOLISE was a US-based trial of 600 patients undergoing MMA embolization using Onyx LES for symptomatic subacute or chronic SDH.  Embolization in addition to surgery was shown to reduce recurrence of SDH compared to surgery alone and was previously published in NEJM 2024.  The non-surgical cohort of the study was presented at ISC, which included 200 patients randomized to MMA embolization vs observation.  Patients did not meet criteria for surgery, thus a key inclusion criterion was midline shift <5mm and hematoma thickness £ 15 mm.  The primary endpoint was 90-day composite of adjudicated need for surgery, poor clinical outcome, or clinical deterioration.  MMA embolization showed significant benefit over observation alone with Relative Risk 0.51 (P=0.04, 95% CI 0.25-0.98), and NNT of 9 patients. 

In summary, there were many high impact trials presented as well as lively debate on how to best integrate updated guidelines into individual practice.