Highlights
– In a 523‑patient international cohort (2010–2024), IV thrombolysis (IVT) alone was associated with higher odds of favorable 3‑month outcome (mRS 0–3) and lower mortality than endovascular thrombectomy (EVT) with or without IVT after inverse probability weighting adjustment.
– Adjusted effect sizes: mRS 0–3 aOR 2.33 (95% CI 1.31–4.12); mRS 0–2 aOR 1.93 (95% CI 1.12–3.30); mortality aOR 0.53 (95% CI 0.29–0.97). Symptomatic intracranial hemorrhage rates did not differ significantly.
– Findings are hypothesis‑generating; residual confounding and nonrandomized treatment allocation limit causal inference. Prospective randomized trials comparing IVT and EVT in BAO are needed.
Background and clinical context
Basilar artery occlusion (BAO) causes brainstem ischemia with very high morbidity and mortality if recanalization is not achieved promptly. Clinical presentations range from vertigo and cranial nerve deficits to coma and “locked‑in” syndrome, and outcomes correlate strongly with time to reperfusion, baseline deficit severity, and extent of brainstem ischemia. Treatment options for acute BAO include intravenous thrombolysis (IVT) with alteplase (or tenecteplase where available) and endovascular thrombectomy (EVT) using stent‑retrievers or aspiration techniques.
Randomized controlled trials have established a clear benefit for EVT in anterior circulation large‑vessel occlusion. For BAO the evidence base has been more heterogeneous: a mix of observational series and several randomized trials have reported varying results, and many trials enrolled only a minority of patients treated with prior IVT. Consequently, optimal initial reperfusion strategy for BAO—IVT, EVT, or a strategy that prioritizes IVT when eligible—remains an unsettled clinical question.
Study design and methods
Räty et al. conducted an international, observational, retrospective cohort study across six centers, including consecutive patients with acute BAO who received either IVT alone or EVT (with or without prior IVT) between January 2010 and March 2024. The analysis included 523 patients: 151 (28.9%) treated with IVT alone and 372 (71.1%) treated with EVT ± IVT.
Primary outcome: functional independence defined as modified Rankin Scale (mRS) score 0–3 at 3 months. Secondary outcomes: mRS 0–2, ordinal shift in mRS, 3‑month mortality, and symptomatic intracranial hemorrhage (sICH).
Because treatment allocation was nonrandomized and baseline characteristics differed, the investigators used inverse probability‑weighted regression adjustment (IPWRA) to control for confounders. Models adjusted for established predictors of outcome in BAO (including baseline National Institutes of Health Stroke Scale [NIHSS], age, imaging ischemic extent, onset‑to‑treatment time) and variables that differed between groups. Interaction tests assessed whether treatment effect varied by symptom severity or onset‑to‑treatment time.
Key findings
Baseline characteristics
Median age across the cohort was 69 years and 35.2% were women. Patients receiving IVT alone had lower median NIHSS (11 vs 15), indicating milder presentation on average versus the EVT group. Baseline imaging showed similarly extensive ischemic changes between groups, however.
Primary and secondary outcomes (adjusted)
After IPWRA adjustment, IVT alone was associated with superior outcomes:
- mRS 0–3 at 3 months: adjusted odds ratio (aOR) 2.33 (95% CI 1.31–4.12)
- mRS 0–2 at 3 months: aOR 1.93 (95% CI 1.12–3.30)
- Ordinal shift to lower (better) mRS: aOR 1.81 (95% CI 1.21–2.71)
- Lower mortality at 3 months: aOR 0.53 (95% CI 0.29–0.97)
There was no statistically significant difference in symptomatic intracranial hemorrhage between groups (aOR 0.81; 95% CI 0.28–2.36).
Interaction analyses
No significant interactions between treatment group and baseline symptom severity or onset‑to‑treatment time were observed for the primary outcome, suggesting the association favoring IVT was not limited to a particular NIHSS stratum or treatment delay cohort within this dataset.
Interpretation and mechanistic considerations
At face value, the adjusted findings suggest that IVT alone was associated with better functional outcomes and lower mortality than EVT ± IVT in this large, multicenter, real‑world BAO cohort. Several, not mutually exclusive explanations should be considered.
- Selection bias and residual confounding. Patients chosen for IVT alone had lower NIHSS and may have had occlusions more likely to lyse with systemic thrombolysis (e.g., distal basilar or embolic occlusions) or better collateral flow. Although IPWRA adjusts for measured confounders, unmeasured factors (clot composition, occlusion location within the basilar artery, pre‑morbid status, center EVT expertise, or other clinical judgments) can bias results in favor of IVT.
- Heterogeneity of EVT outcomes in BAO. Thrombectomy for BAO can be technically challenging because of tortuosity, underlying atherosclerotic stenosis, tandem disease, and risk of perforator occlusion that disproportionately affects brainstem nuclei. In some centers or cases, EVT may not restore robust microvascular reperfusion even after large‑vessel recanalization, limiting clinical benefit.
- Time and reperfusion biology. IVT is rapid to administer and may achieve early partial reperfusion that limits infarct progression. EVT involves patient transfer, angiography setup, and procedural time; in BAO where even short delays can be critical, the advantage of prompt IVT may carry greater weight in some presentations.
- Complications and rescue treatments. EVT can require rescue stenting or angioplasty for underlying stenosis, increasing risk. On the other hand, IVT may be less effective in large or organized thrombi and could delay definitive EVT when needed; such dynamics are complex and case‑specific.
Safety
Observed rates of symptomatic intracranial hemorrhage were similar between groups after adjustment, indicating that differential bleeding risk likely does not account for the better outcomes with IVT in this cohort. Nonetheless, bleeding remains a central safety consideration when comparing reperfusion strategies and should factor into clinical decision‑making.
Strengths and limitations
Strengths:
- Large, international, multicenter sample reflecting contemporary practice over 14 years.
- Robust statistical approach (IPWRA) to account for measured confounding and baseline imbalances.
- Comprehensive outcomes including functional status, ordinal shift, mortality, and sICH.
Limitations:
- Nonrandomized, retrospective design — treatment allocation was clinician‑directed and susceptible to selection bias and unmeasured confounding.
- Incomplete capture of certain procedural variables (device type, recanalization quality such as modified Thrombolysis in Cerebral Infarction score, operator experience), clot characteristics, and in‑hospital process times that influence outcomes.
- Heterogeneity across centers in imaging protocols, EVT threshold, and post‑procedural care may limit generalizability.
- Temporal changes in EVT devices and technique between 2010 and 2024 could introduce confounding by era.
How this fits with existing evidence
Randomized trials and meta‑analyses in anterior circulation large‑vessel occlusion have established EVT as standard of care when performed promptly and in appropriate patients. For BAO the evidence is less uniform: some trials and registries favor EVT, but results vary by trial design, eligibility windows, and rates of prior IVT. Importantly, some positive BAO trials enrolled many patients treated beyond early time windows and included few who received IVT prior to EVT. Räty et al.’s findings highlight the need to explicitly address initial reperfusion strategy in BAO through trials that ensure adequate IVT use in both arms when eligible.
Clinical implications
For practicing clinicians, key practical takeaways include:
- Do not reflexively equate EVT superiority in anterior circulation with universal superiority in BAO. Individualized assessment is essential.
- When eligible, IVT should remain a time‑sensitive option for BAO and is not contraindicated when EVT is planned — systemic thrombolysis may achieve early reperfusion or facilitate later EVT.
- Decision pathways should consider severity, imaging findings (extent of brainstem ischemia, collaterals), occlusion location, transfer and procedural delays, and center EVT expertise. Rapid multidisciplinary decision‑making is crucial.
Research and policy implications
The study supports the need for randomized controlled trials that directly compare an initial IVT‑first strategy to primary EVT in BAO, or that randomize IVT‑eligible patients to IVT alone versus EVT ± IVT with stratification by time window and occlusion characteristics. Trials should prespecify imaging selection criteria, ensure standardized EVT techniques, and collect granular procedural and technical data (reperfusion grade, passes, rescue therapy, clot histology) to elucidate mechanisms.
Conclusion
In this large, multicenter retrospective cohort, IV thrombolysis alone was associated with better functional outcomes and lower mortality than EVT ± IVT for acute basilar artery occlusion after adjustment for measured confounders. While provocative, these findings are not definitive because of the nonrandomized design and potential for residual confounding. They underscore the urgency of well‑designed randomized trials to define the optimal reperfusion strategy in BAO and remind clinicians to preserve IVT as a rapid, effective option when patients are eligible.
Funding and clinicaltrials.gov
The study authors report funding details in the original publication; anonymized individual patient data are available on reasonable request to the corresponding author per national legislation. No ClinicalTrials.gov registration applies to this retrospective cohort study. Readers should consult the original paper for detailed funding disclosures.
References
1. Räty S, Strambo D, Gomez‑Exposito A, Marto JP, Ramos JN, Krebs S, Virtanen P, Ritvonen J, Abdalkader M, Klein P, Sairanen T, Sykora M, Lindsberg PJ, Poli S, Michel P, Nguyen TN, Strbian D. Intravenous thrombolysis versus endovascular thrombectomy in acute basilar artery occlusion—A multicenter cohort study. Int J Stroke. 2025 Oct;20(9):1114–1122. doi:10.1177/17474930251344451. PMID: 40356017; PMCID: PMC12521756.
2. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46–e110.
Thumbnail prompt for AI image generation
A high-resolution clinical illustration: a neuroradiologist and stroke neurologist reviewing axial CT angiography and perfusion maps on dual monitors, with an inset schematic of a basilar artery clot and a syringe labeled “tPA” and a microcatheter — muted blues and grays, clinical lighting, modern hospital setting.
