The research team, led by Martin Vychopen of University Hospital Leipzig together with colleagues including neuroradiologist Karl-Titus Hoffmann and neurosurgeons Erdem Güresir and Johannes Wach, pooled data from six randomized controlled trials encompassing up to 3,044 patients treated for ruptured intracranial aneurysms. Rather than simply averaging outcomes across all patients, as many earlier meta-analyses have done, the investigators stratified their analysis by aneurysm location and by the neurological severity of the hemorrhage at admission, measured on the World Federation of Neurosurgical Societies scale. This anatomically informed approach matters because an aneurysm tucked into the delicate branches of the middle cerebral artery presents a fundamentally different surgical and endovascular challenge than one sitting on the internal carotid artery near the skull base.

The headline finding concerns functional outcome at one year, assessed with the modified Rankin Scale, the standard yardstick of disability after stroke. When the researchers defined a favorable outcome as a score of 0 to 2, meaning the patient is independent in daily life, coiling came out clearly ahead. Across the pooled cohort of 3,044 patients, the odds of achieving independence at one year were 60 percent higher after endovascular coiling than after microsurgical clipping, an odds ratio of 1.60 with a 95 percent confidence interval of 1.36 to 1.88 and a p-value below 0.00001. Critically, heterogeneity across the six trials was essentially zero, indicating that the trials told a remarkably consistent story despite spanning more than two decades of practice.

But here is where the analysis turns provocative. When the team re-ran the numbers using a broader cut-off, defining favorable outcome as a modified Rankin Scale score of 0 to 3, the statistically significant advantage of coiling evaporated entirely. In that analysis of 2,278 patients from three trials, the odds ratio shrank to 1.19 with a p-value of 0.12, well short of significance. The implication is striking: much of the celebrated benefit of coiling may hinge on where exactly the disability scale is divided. This echoes long-standing critiques of the original International Subarachnoid Aneurysm Trial, or ISAT, whose landmark 2005 result established coiling as the preferred treatment in many centers worldwide. Commentators had previously argued that the binary 0-to-2 versus 3-to-6 split was insufficiently sensitive, and the new pooled data, which incorporate the more recent ISAT-2 trial by Darsaut and colleagues, lend quantitative weight to that concern.

The location-specific results are arguably the most clinically actionable part of the study. For aneurysms of the internal carotid artery, coiling delivered a decisive advantage in functional outcome, with an odds ratio of 0.44 favoring coiling, a difference that was highly significant with a p-value below 0.00001 and zero heterogeneity. The authors attribute this to the particular hazards of microsurgical access in this territory: internal carotid artery aneurysms, especially those arising at the ophthalmic segment or the carotid bifurcation, sit in a region where achieving proximal control of the vessel during open surgery can be difficult and may require additional measures to reduce blood flow, raising the morbidity of the surgical approach.

In contrast, no significant difference in one-year functional outcome emerged for aneurysms of the anterior cerebral artery and anterior communicating artery, the middle cerebral artery, or the posterior circulation. For anterior communicating aneurysms, which frequently rupture at small sizes and are associated with complex anatomy such as hypoplasia of the A1 segment, the pooled data support an individualized, anatomy-based decision rather than a default preference for either technique. For posterior circulation aneurysms, which carry elevated in-hospital mortality and a higher incidence of acute hydrocephalus, the analysis was limited by the underrepresentation of basilar and cerebellar aneurysms in prospective randomized trials, a caveat the authors acknowledge openly.

Where clipping decisively reasserts itself is in the durability of aneurysm closure. When the researchers examined complete occlusion confirmed on angiography twelve months after treatment, pooling four trials and 1,889 patients, surgical clipping was clearly superior, with an odds ratio of 0.35, a 95 percent confidence interval of 0.28 to 0.44, and again no heterogeneity. This overall effect, however, was driven almost entirely by one subgroup: middle cerebral artery aneurysms, where the odds of complete occlusion after clipping were more than five times those after coiling, an odds ratio of 5.21 with a p-value of 0.007. For internal carotid, anterior cerebral, and posterior circulation aneurysms, complete occlusion rates did not differ significantly between the two modalities. The anatomical explanation is compelling: middle cerebral artery aneurysms often resemble complex bifurcation lesions rather than simple sacs, frequently involving wide necks and critical branch vessels, and clipping in this location allows the surgeon to preserve distal flow while minimizing the risk of injury to small perforating arteries.

Why does complete occlusion matter so much? Because an incompletely closed aneurysm can reopen, and a reopened aneurysm can bleed again, sometimes catastrophically. The ARETA study found that roughly 20 percent of coiled aneurysms exhibit reopening or neck remnants, with about half of those requiring retreatment, while the CARAT investigation linked the risk of early rebleeding directly to the degree of aneurysm occlusion achieved. The Barrow Ruptured Aneurysm Trial further demonstrated that complete clip occlusion offers superior treatment durability, significantly reducing the need for repeat procedures, and both endovascular and microsurgical retreatment carry higher perioperative complication rates than the original intervention. Achieving complete obliteration in a single procedure therefore remains one of the central therapeutic goals in this disease.

Mortality, meanwhile, refused to pick a side. Across six trials and 2,921 patients, all-cause mortality did not differ between coiling and clipping, with an odds ratio of 0.89 and a p-value of 0.35. The severity-stratified analysis added another layer: among patients with good clinical grades, defined as WFNS grade 3 or better, coiling was associated with significantly better functional outcomes across 2,213 patients, whereas among the 168 patients with the worst grades, WFNS greater than 3, neither technique showed a significant advantage, likely reflecting the dominant influence of the initial brain injury itself on prognosis in severely affected patients.

The authors are careful about the limits of their work. The included trials span more than two decades, during which both endovascular devices and microsurgical techniques have evolved considerably, and modern adjuncts such as the Woven EndoBridge device and stent-assisted coiling are not yet represented in randomized subgroup data. Patients with posterior circulation aneurysms and high-grade hemorrhage remain underrepresented, and complete occlusion was a secondary endpoint in the original trials rather than a pre-specified primary one, introducing the possibility of distribution bias since aneurysm location was not randomly balanced across treatment arms. Risk-of-bias assessment using the Cochrane 2.0 tool rated ISAT and the Barrow Ruptured Aneurysm Trial as low risk across all domains, while other trials raised concerns ranging from unclear randomization to selective reporting. Even so, the core message stands with unusual clarity for a field long divided by tribal loyalties: for a ruptured internal carotid artery aneurysm, the catheter likely holds the edge in preserving independence at one year; for a ruptured middle cerebral artery aneurysm, the clip remains the gold standard for sealing the lesion completely and durably; and for everything in between, the decision deserves to be made aneurysm by aneurysm, patient by patient, balancing the promise of functional recovery against the imperative of permanent closure.

Subject of Research: Comparative effectiveness of endovascular coiling versus microsurgical clipping for ruptured intracranial aneurysms

Article Title: Efficacy and safety of endovascular coiling compared to microsurgical clipping in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of randomized trials

Article References: Vychopen, M., Hoffmann, K.-T., Güresir, E., & Wach, J. (2026). Efficacy and safety of endovascular coiling compared to microsurgical clipping in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of randomized trials. Journal of Neurology, 273(10), Article 650. https://doi.org/10.1007/s00415-026-14150-z

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14150-z

Keywords: aneurysmal subarachnoid hemorrhage, endovascular coiling, microsurgical clipping, intracranial aneurysm, meta-analysis, randomized controlled trials, modified Rankin Scale, middle cerebral artery, internal carotid artery, complete occlusion, ISAT, neurosurgery