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.

Tenecteplase has replaced alteplase as the default IV thrombolytic

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

The drug that wins on workflow wins on outcomes. The pharmacology is not the whole story.

The 2024 American Heart Association/American Stroke Association focused update on stroke thrombolysis upgraded tenecteplase (0.25 mg/kg, maximum 25 mg) to a Class IIa recommendation as a reasonable alternative to alteplase. Most US comprehensive stroke centers have now adopted tenecteplase as the default agent.

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 11 European countries: in patients with ASPECTS 3–5, mRS shift analysis favored thrombectomy with a generalized odds ratio of 2.58.7

What changed in practice

The 2024 AHA/ASA guideline update gives a Class I recommendation for thrombectomy in patients with ASPECTS 3–5 who meet other selection criteria. Centers that previously excluded these patients are now treating them — though with attention to hemorrhagic transformation risk, which remains higher than in small-core populations.

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

Both trials terminated early for benefit. Together they establish basilar thrombectomy as standard of care — 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

TIMING and START have produced concordant signals. The aggregate evidence supports earlier-than-traditional anticoagulation initiation, with the trade-off being modestly higher hemorrhagic transformation risk balanced against measurable reduction in recurrent ischemia. The cardioembolic patient who in 2015 waited a week now leaves on apixaban on hospital day two or three.

Late-window thrombectomy by tissue selection

DAWN (Nogueira et al., NEJM 2018) and DEFUSE-3 (Albers et al., NEJM 2018) reframed the question of who could be treated by replacing the clock with the brain. Patients selected by perfusion imaging — with small ischemic cores and large salvageable tissue volumes — benefited from thrombectomy out to 24 hours from last-known-well.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 (Grotta et al., NEJM 2021) randomized patients in seven US cities to mobile stroke unit dispatch versus standard EMS. Among 617 thrombolysis-eligible patients, 55.0% achieved an excellent 90-day outcome (utility-weighted mRS) with MSU care versus 44.4% with standard EMS — a clinically and statistically significant improvement.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

The clinical question is settled. The remaining questions concern population density, EMS volume, and the cost-effectiveness math by which a given community decides whether to deploy an MSU.

Artificial intelligence in stroke imaging

Automated perfusion software is no longer the exotic tool it was in 2015. Most thrombectomy-capable centers, and an increasing number of primary stroke centers, now run automated post-processing for ASPECTS scoring, large-vessel-occlusion detection, and perfusion-based core/penumbra estimation. Commercial platforms (RAPID, Viz.ai, e-ASPECTS, Brainomix) have been validated against human readers and shortened door-to-puncture times in real-world deployment studies.

None of this replaces a careful eye on raw imaging. All of it shortens the time between scanner and decision — and, in transfer networks, between hub and spoke.

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.