A randomised controlled trial (RCT) involving more than 200 patients has indicated that stent-assisted coiling (SAC) is not superior to coiling alone in unruptured intracranial aneurysm cases with a high risk of recurrence.
Reporting results from the STAT trial in the American Journal of Neuroradiology (AJNR), William Boisseau (Centre Hospitalier de l’Université de Montréal, Montreal, Canada) et al detail that the approach was unable to demonstrate better treatment failure-related outcomes than standard coiling across patients with wide-neck, large or recurrent aneurysms.
“The use of stents for the treatment of unruptured intracranial aneurysms is an example of the failure of our community to use randomised trials to safely introduce innovations in neurovascular care,” Boisseau et al state. “We must find ways to integrate clinical research into practice to optimise care in real time. Future trials on SAC should probably be integrated into ongoing randomised clinical trials.”
The authors also note that, while their study excluded patients with ruptured aneurysms; patients subjectively adjudged to be “untreatable” without stent placement; and the majority of patients with small unruptured aneurysms, it ultimately showed “no large benefit” to a policy of stent placement plus coiling. Additionally, they feel the trial “raises concerns” regarding potential thromboembolic complications—particularly in patients with small aneurysms at a low risk of rupture, “for whom the crucial question remains: should they be offered preventive treatment at all?”
Backdrop to STAT
While they affirm at the outset of their AJNR paper that SAC may be associated with improved angiographic results in endovascular unruptured aneurysm treatments, as compared to coiling alone, the authors aver “this has never been shown in a randomised trial”.
With this in mind, the investigator-led, parallel STAT RCT was set up and conducted across four university hospitals in Canada and France. The trial saw patients with intracranial aneurysms at risk of recurrence (defined as large aneurysms [≥10mm], post-coiling recurrent aneurysms or small aneurysms with a wide neck [≥4mm]) undergo 1:1 randomisation to either SAC or coiling alone.
The trial’s primary efficacy outcome was a composite endpoint of ‘treatment failure’—defined as initial failure to treat the aneurysm; aneurysm rupture or retreatment during follow-up; death or dependency (modified Rankin scale [mRS] >2); or an angiographic residual aneurysm adjudicated by an independent core laboratory at 12 months.
Boisseau et al also detail that their primary hypothesis was that SAC would decrease treatment failure rates from 33% to 15%, with an intention-to-treat population of 200 patients being required to sufficiently assess this. This differed from an initial efficacy hypothesis that SAC would decrease angiographic recurrences by 20% at 12 months, as per the trial’s original 2011 protocol, which was modified in July 2021 “before any knowledge of the data”.
New coiling data
Of 205 patients recruited between 2011 and 2021, 94 were allocated to SAC and 111 to coiling alone, the authors report. The key results from STAT are as follows:
- The primary outcome, ascertainable in a total of 203 patients, was reached in 28/93 patients allocated to SAC (30.1%) versus 30/110 allocated to coiling alone (27.3%; p=0.66).
- Poor clinical outcomes (mRS >2) occurred in 8/94 SAC patients (8.5%) compared with 6/111 coiling-only patients (5.4%; p=0.38).
- There were no incidences of aneurysm rupture during follow-up and three patients—all in the SAC group—were retreated.
- Five deaths were related to treatment complications (three with SAC and two with coiling alone), while adverse events occurred in 25/94 SAC patients (26.6%) and 23/111 coiling-only patients (20.7%; p=0.323).
- Secondary outcomes, including immediate and 12-month angiographic outcomes; days of hospitalisation; discharge disposition; and mRS at discharge and at 12 months; were all similar between groups too.
Boisseau et al also note that predefined subgroup analyses of the primary outcome found no significant interactions, with similar results across different subgroups, and “only by redefining a good angiographic outcome as complete occlusion [rather than a combination of complete and near-complete occlusion]—and only by looking at as-treated analyses—could SAC be shown superior to coiling alone”.
What are the implications?
“The clinical significance of this finding remains questionable, but it may be a signal in favour of the capacity of stent placement to improve angiographic results of coiling in the long term,” they continue. “This capacity may come at a cost in terms of complications: as-treated analyses also showed complications to be more frequent with SAC, particularly for small aneurysms. Although in some of these cases complications occurred when stents were being used as a rescue strategy, thromboembolic complications with stent placement remain a concern.”
Reflecting on their results, the authors also posit that STAT was only powered to show a ‘large effect’, claiming that “we cannot exclude that, with the inclusion of a larger number of patients, a more modest but still clinically significant benefit could have been demonstrated”. They further state that a substantial number of crossover patients could have diluted the contrast between treatments in the trial, and that “perhaps, the groups being compared could have been more precisely defined” as SAC (if possible) versus coiling alone plus bailout stent placement (only if necessary).
The overall morbidity and mortality rates in STAT were within the investigators’ initial estimate of 6–12%, as per a secondary hypothesis suggesting stent placement “would not double” the number of dead or dependent (mRS >2) patients at 12 months—a hypothesis that was also dropped in July 2021. However, while safety endpoints were similar between the two groups in intention-to-treat analyses, the authors concede that the trial was “underpowered to draw any conclusions about the safety of SAC over coiling alone”.
STAT is the only RCT to date comparing SAC and coiling alone, according to Boisseau et al. Nevertheless, owing to the many questions it failed to answer conclusively, as well as other limitations present in the trial—including small numbers of centres and patients stunting the generalisability of the data, and the fact that clinical practices evolved over the 10-year study period—they conclude that more randomised data are needed to determine the role of SAC in the treatment of aneurysms. The authors further note that, as such, the “context of uncertainty” within which STAT was launched in 2011 persists today.