Clinical outcomes before and after the introduction of clazosentan in aneurysmal subarachnoid hemorrhage: a multicenter retrospective study of clipping and endovascular treatment.
Takeuchi I, Muraoka S, et al. • Neurosurgical review • 2026
Favorable functional outcomes were significantly more frequent in the EVT group than in the clipping group overall, but the between-group difference observed in the fasudil era was not statistically significant in the clazosentan era, though formal interaction testing did not confirm significant effect modification.
Key Findings
Results
Overall, favorable outcomes at discharge (mRS 0-2) were significantly more frequent in the EVT group than in the clipping group.
59.2% of EVT patients vs 48.4% of clipping patients achieved mRS 0-2 at discharge (p = 0.004).
A total of 496 patients were analyzed from the RECOVER registry between 2021 and 2024.
57.5% of patients underwent microsurgical clipping; the remainder underwent endovascular treatment.
Multivariable analyses adjusted for age, WFNS grade, Fisher group, anterior circulation aneurysm, and use of cerebrospinal fluid drainage.
Results
In the fasudil era, the EVT group showed a significantly higher proportion of favorable outcomes than the clipping group, but this difference was not statistically significant in the clazosentan era.
The apparent reduction in between-group differences in the clazosentan era should be interpreted with caution as formal interaction testing did not identify statistically significant effect modification.
The authors describe these era-based observations as 'hypothesis-generating.'
Results
Functional outcomes appeared more favorable in both the clipping and EVT groups during the clazosentan era compared to the fasudil era.
Clipping group favorable outcomes increased from 41.5% (fasudil era) to 62.7% (clazosentan era).
EVT group favorable outcomes increased from 59.0% (fasudil era) to 72.6% (clazosentan era).
Clazosentan has been available in Japan since 2022, whereas fasudil was the traditional perioperative pharmacological agent for cerebral vasospasm prevention.
The study period was divided into the fasudil era and clazosentan era corresponding to before and after clazosentan's introduction.
Results
The incidence of vasospasm-related delayed cerebral ischemia (DCI) was not significantly different between the EVT and clipping groups, although it was numerically lower in the EVT group.
Vasospasm-related DCI was a prespecified secondary endpoint.
No statistically significant between-group difference was reported for DCI incidence.
Delayed cerebral ischemia is described as 'one of the most important determinants of clinical outcomes after treatment for aneurysmal subarachnoid hemorrhage.'
Secondary endpoints also included cerebral vasospasm, pulmonary complications, hypotension, cerebral edema, and new intracranial hemorrhage.
Methods
The study used a multicenter retrospective registry design analyzing patients who underwent definitive treatment within 48 hours of aSAH onset.
Data were drawn from the RECOVER registry, covering the period 2021–2024.
Inclusion criteria required definitive treatment (clipping or EVT) within 48 hours of onset and receipt of either fasudil or clazosentan.
The primary endpoint was favorable functional outcome at discharge defined as mRS score of 0–2.
The retrospective design and absence of statistically significant interaction testing limit causal interpretation of era-based differences.
What This Means
This research examined outcomes for patients who suffered a brain bleed caused by a ruptured aneurysm (aneurysmal subarachnoid hemorrhage) and were treated with either surgical clipping or a minimally invasive endovascular procedure. The study also looked at whether the introduction of a newer medication called clazosentan—used to prevent dangerous blood vessel narrowing (vasospasm) in the brain after such bleeds—changed the comparison between these two treatment approaches. Data from 496 patients treated at multiple centers in Japan between 2021 and 2024 were analyzed.
Overall, patients treated with endovascular methods were more likely to have a good functional recovery at hospital discharge (about 59%) compared to those who had surgical clipping (about 48%). Before clazosentan became available, this gap was large and statistically significant (59% vs 42%). After clazosentan was introduced, both groups appeared to do better, and the gap between them narrowed and was no longer statistically significant (73% vs 63%). However, the authors caution that formal statistical testing did not confirm that clazosentan specifically changed the relationship between treatment type and outcome, so this finding should be considered preliminary and hypothesis-generating rather than definitive.
This research suggests that the availability of clazosentan may be associated with improved outcomes for aSAH patients regardless of whether they receive surgical or endovascular treatment, and potentially narrows the outcome difference between the two approaches. However, because this was a retrospective (look-back) study without randomization, definitive conclusions cannot be drawn. The authors call for prospective studies to confirm whether clazosentan is truly responsible for the observed improvements and whether it specifically affects the relative benefit of one treatment over the other.
Takeuchi I, Muraoka S, Kinoshita F, Izumi T, Ishii K, Nishihori M, et al.. (2026). Clinical outcomes before and after the introduction of clazosentan in aneurysmal subarachnoid hemorrhage: a multicenter retrospective study of clipping and endovascular treatment.. Neurosurgical review. https://doi.org/10.1007/s10143-026-04469-6