If you trained in stroke neurology a decade ago, the field is recognizable but no longer identical. The bones are the same: the NIHSS, the four-and-a-half-hour window for intravenous thrombolysis, the basic anatomy of an arterial territory. The flesh has changed. The thrombolytic agent has shifted. The catheter is doing more work. The window has stretched. And the way we select patients has moved from a clock to a tissue clock — from "when did this start" to "what does the brain still look like."

What follows is a review of the major shifts in acute stroke practice since 2020, organized around the trials that drove each change. None of them, individually, will overturn a stroke program. Together, they describe a field that is unmistakably moving. Current recommendations are in the 2026 stroke guideline changes.

Tenecteplase became an evidence-supported alternative

The most consequential change in acute thrombolysis is not a new drug — it is one we have had in cardiology for two decades. Tenecteplase is a genetically modified variant of alteplase with three relevant pharmacologic differences: 14-fold greater fibrin specificity, an 80-fold greater resistance to plasminogen activator inhibitor 1, and a longer half-life that permits single-bolus dosing rather than a 60-minute infusion.1

The pivotal trial was AcT (Menon et al., Lancet 2022), a Canadian pragmatic randomized non-inferiority study of 1,577 patients with acute ischemic stroke within 4.5 hours of symptom onset.1 The proportion of patients achieving an excellent functional outcome (mRS 0–1) at 90 days was 36.9% with tenecteplase versus 34.8% with alteplase, meeting the pre-specified non-inferiority margin. Rates of symptomatic intracerebral hemorrhage and mortality were comparable between groups.

TRACE-2 (Wang et al., Lancet 2023), conducted in 1,430 patients in China, replicated the finding: 62% of tenecteplase-treated patients reached mRS 0–1 versus 58% with alteplase, again meeting non-inferiority.2 The TASTE-A trial demonstrated that mobile-stroke-unit administration of pre-hospital tenecteplase produced superior early reperfusion compared with alteplase.3

A simpler workflow is valuable, but it does not by itself establish superior clinical outcomes.

For current recommendations, use the 2026 AHA/ASA guideline summary and its linked full guideline. Older trial findings explain how practice evolved; they do not establish a current institution’s preferred agent or complete eligibility criteria.

Large-core thrombectomy is now evidence-based

For nearly a decade after the 2015 thrombectomy trials, ASPECTS 6 or greater (i.e., a small ischemic core on baseline CT) was a near-absolute requirement for endovascular therapy. Three trials published between 2022 and 2023 fundamentally changed that boundary.

RESCUE-Japan LIMIT (Yoshimura et al., NEJM 2022) randomized 203 patients with ASPECTS 3–5 and demonstrated that the proportion achieving mRS 0–3 at 90 days was 31.0% with thrombectomy versus 12.7% with medical management alone (relative risk 2.43; 95% CI 1.35–4.37).4

SELECT2 (Sarraj et al., NEJM 2023) enrolled 352 patients with ischemic core volumes of 50 mL or greater, or ASPECTS 3–5. The thrombectomy arm had a generalized odds ratio of 1.51 for shift toward lower disability on the modified Rankin Scale, with 20.3% achieving functional independence (mRS 0–2) versus 7.0% with medical management.5

ANGEL-ASPECT (Huo et al., NEJM 2023) studied 456 patients with ASPECTS 3–5 or large core volumes and demonstrated a similar shift toward better outcomes with thrombectomy.6

The European TENSION trial (Bendszus et al., Lancet 2023) extended the finding to clinical practice in its trial population: in patients with ASPECTS 3–5, mRS shift analysis favored thrombectomy with a generalized odds ratio of 2.58.7

What changed in practice

Large-core trials expanded the evidence base. Apply the current guideline’s complete selection criteria rather than treating an ASPECTS value as sufficient by itself. See who qualifies for thrombectomy.

Basilar artery thrombectomy is standard of care

Posterior-circulation stroke has historically lagged the anterior circulation in trial evidence. Two 2022 trials closed the gap.

ATTENTION (Tao et al., NEJM 2022) randomized 340 Chinese patients with basilar artery occlusion within 12 hours of symptom onset. Good functional outcomes (mRS 0–3) at 90 days occurred in 46% of the thrombectomy arm versus 23% of the medical-management arm — a more than doubling of the favorable outcome rate.8

BAOCHE (Jovin et al., NEJM 2022) extended the window to 6–24 hours from estimated time of basilar occlusion. Good outcomes occurred in 46% with thrombectomy versus 24% with medical management.9

These trials support thrombectomy in selected basilar occlusion patients — a substantial reversal from the equivocal BEST and BASICS trials of the prior decade, and one of the most clinically important pieces of evidence in posterior-circulation stroke in twenty years.

Early anticoagulation after cardioembolic stroke

For most of the past two decades, the timing of anticoagulation initiation after cardioembolic stroke in atrial fibrillation was governed by a heuristic — the 1-3-6-12-day rule — indexed to infarct size. Four contemporary trials have replaced that heuristic with data.

ELAN (Fischer et al., NEJM 2023) randomized 2,013 patients to early (within 48 hours for minor or moderate stroke; days 6–7 for major stroke) versus later (days 3–4 for minor, days 6–7 for moderate, days 12–14 for major) initiation of a direct oral anticoagulant. The composite outcome of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days occurred in 2.9% of early-treatment patients versus 4.1% of later-treatment patients — a non-significant trend favoring early initiation, with no excess intracranial hemorrhage.10

OPTIMAS (Werring et al., Lancet 2024) enrolled 3,648 patients and tested non-inferiority of early (≤4 days) versus standard (7–14 days) DOAC initiation. Early initiation met non-inferiority for the primary composite of recurrent stroke, systemic embolism, symptomatic ICH, or unclassifiable stroke at 90 days, with no increase in symptomatic intracranial hemorrhage.11

Do not convert a trial’s “early” arm into a universal day-two prescription. Infarct size, hemorrhagic transformation, other bleeding risks and the indication for anticoagulation must be considered. The schedules differed between trials, and stroke-risk scores do not determine the start date.

Late-window thrombectomy by tissue selection

DAWN (2018) studied selected patients 6–24 hours from last-known-well using a clinical–core mismatch. DEFUSE 3 (2018) studied selected patients 6–16 hours using perfusion-based criteria. These trials expanded eligibility within defined time and imaging limits; they did not abolish the clock.1213

These trials remain practice-defining for the late-window population. Their indirect effect on the rest of acute stroke practice has been to shift the conceptual frame: the question is no longer whether a patient is too late, but whether the imaging tells us that they are not.

Mobile stroke units

BEST-MSU (2021) was a prospective controlled study using alternating service weeks, not individual randomization. It associated mobile stroke-unit care with better 90-day outcomes among thrombolysis-eligible patients. Its primary measure was the utility-weighted modified Rankin Scale.14

The European B_PROUD study (Ebinger et al., JAMA 2021) reached parallel conclusions: MSU dispatch was associated with lower 90-day disability scores in thrombolysis-eligible patients.15

Implementation still depends on the local emergency system, availability and resources. Families should call emergency services rather than wait for a particular ambulance type.

Artificial intelligence in stroke imaging

Automated tools can assist with selected imaging tasks. Performance and clinical effect depend on the product, task, population and workflow; a single claim cannot describe every commercial platform. Clinicians must review the underlying images and recognize potential errors.

Software output supplements clinical and imaging assessment. It must not be treated as an independent treatment authorization.

What is not changing

The bedside exam still matters. The NIHSS still anchors clinical decisions in settings where imaging is delayed or ambiguous. Risk-factor management — blood pressure, lipids, glucose, smoking, atrial fibrillation detection — is still where most secondary prevention actually lives. The most sophisticated thrombectomy program in the world will not outrun a community that does not control blood pressure.

So: the field is moving, but not abandoning its center of gravity. The work is the same work it was. The tools are sharper. The windows are longer. The thrombolytic pours from a single syringe. The brain is, fractionally, getting more of itself back. After the acute phase, see the stroke recovery timeline and why early stroke rehabilitation matters. For ongoing coverage, see the latest stroke research updates.