Subarachnoid hemorrhage (SAH) is a rare subtype of stroke, constituting 2–5% of all stroke cases. Among SAH cases, 85% are attributed to the rupture of intracranial aneurysms (ICA), known as aneurysmal subarachnoid hemorrhage (aSAH) (1). The annual incidence rate of aSAH is approximately 7.9 per 100,000 individuals, with the highest occurrence observed between the ages of 40 and 60 (2–4). Despite advancements in diagnostic and treatment approaches that have led to a reduced mortality rate for aSAH, a significant proportion of survivors are left with long-term consequences (5). Cerebral vasospasm (CV) is a common complication of aSAH, typically manifesting between the 3rd and 14th day following SAH, with the highest incidence observed between the 7th and 10th day (6–8). Approximately 30–70% of aSAH patients may develop angiographic vasospasm, and among them, half may experience delayed cerebral ischemia (DCI). Ultimately, even with maximal treatment, approximately 15–20% of patients face infarction or mortality (9).

The treatment of CV remains a subject of extensive debate, with limited available treatment options (10). According to the American Heart Association (AHA) guidelines, all patients with aSAH should receive oral nimodipine (Class I; Level of Evidence A) as it reduces the risk of DCI and improves neurological outcomes. For refractory cases that do not respond to standard treatment, AHA suggests that endovascular therapy may be a reasonable option (Class IIa; Level of Evidence B) (11). Over time, endovascular therapy has gained widespread clinical application and has emerged as an alternative treatment for CV, challenging the traditional standard therapy (12–14). Endovascular therapy encompasses two methods: transluminal balloon angioplasty (TBA) and intra-arterial vasodilator infusion (IAV/IAVI). TBA is suitable for acute-phase CV and provides rapid and direct effects, but is limited to proximal vessels and focal cerebral vasospasm (15, 16). IAVI is another commonly used endovascular treatment for CV, involving the direct delivery of vasodilatory drugs into the spastic vessel via a catheter. This approach aims to dilate the narrowed vessel and increase cerebral blood flow. Commonly used drugs include nitroprusside, calcium channel blockers (such as nimodipine, nicardipine, and verapamil), and the selective phosphodiesterase-3 inhibitor milrinone, et al. (17–19). IAVI can be employed during the acute or subacute phase and is suitable for managing more distal and diffuse vessel spasms.

Currently, the superiority of endovascular therapy over standard treatment remains a subject of controversy, despite it being considered as a salvage treatment after standard therapy failure. The clinical literature reports considerable variation in the outcomes. Given these discrepancies, we conducted a systematic review and meta-analysis to compare the effects of endovascular therapy and standard treatment on post-aSAH cerebral vasospasm. The objective is to provide recommendations for clinicians in selecting treatment strategies and offer guidance for the design of future clinical trial protocols.

Cerebral vasospasm is a prevalent and severe complication following aneurysmal subarachnoid hemorrhage (1, 31, 32). This condition imposes a significant burden on patients’ prognosis and economic status, with studies reporting that 25–50% of patients may experience disabilities, while only 30–45% are able to recover to their previous work status (33). Additionally, patients undergoing treatment for CV face an additional economic burden of up to 30% compared to those without CV (34). Hence, timely and effective treatment for cerebral vasospasm is crucial in improving patients’ prognosis and quality of life. Currently, there is no consensus on the treatment approach for CV in the existing treatment guidelines. Therefore, we conducted this meta-analysis to assess the efficacy and safety of endovascular therapy compared to standard treatment in patients with CV. Our objective is to furnish novel insights and recommendations for the management of CV through this meta-analysis, ultimately aiming to enhance patients’ recovery and survival outcomes in the future.

The results of this study indicate that endovascular therapy leads to a perioperative mortality rate that is only half of that observed with standard treatment. Subgroup analysis reveals that this outcome is primarily driven by the IAVI group, where patients receiving both IAVI and TBA exhibit no significant difference in in-hospital mortality compared to standard treatment. This highlights the significant advantage of IAVI in reducing the risk of in-hospital mortality, effectively halving the rate and holding crucial implications for saving patients’ lives. However, it is noteworthy that no significant differences are observed between the IAVI and standard treatment groups concerning the discharge favorable outcomes and follow-up favorable outcomes. In secondary outcomes, patients receiving IAVI show no significant differences in terms of major infarction, ICU stay duration, and total hospital stay when compared to those undergoing standard treatments. This indicates that, although IAVI can reduce perioperative mortality compared to standard treatment, it does not significantly improve patients’ recovery and long-term prognosis, nor does it completely eliminate or reduce the risk of severe infarctions. Nevertheless, this does not imply that IAVI lacks potential benefits. Other factors may have contributed to these results, such as insufficient sample size or inadequate follow-up duration. Furthermore, patients’ recovery and prognosis may be influenced by multiple factors beyond the treatment method. Despite the lack of long-term advantages in prognosis, the clear short-term efficacy of IAVI is evident. Its ability to lower in-hospital mortality is undeniably beneficial for patients and represents a critical clinical achievement, leading us to recommend IAVI as a valuable option for treating cerebral vasospasm. On the other hand, the neurological functional recovery provided by IAVI for cerebral vasospasm is limited, necessitating its combination with other rehabilitation and support measures to optimize treatment strategies and improve patients’ quality of life and functional recovery.

Currently, there is significant controversy in the clinical setting regarding the effectiveness of TBA treatment for CV (20, 35). Some studies have conducted retrospective evaluations to explore the feasibility and efficacy of TBA treatment. Tsogkas et al. (36) conducted a study retrospectively evaluating 17 patients who received Scepter C balloon catheter treatment between 2014 and 2018. These patients were successfully treated for CV after failed medical therapy, with no associated complications. Some researchers have also conducted a similar study, demonstrating the feasibility of Scepter C balloon catheter treatment for CV (37). Another research supports TBA as a therapeutic option for severe proximal vessel spasm and reduced tissue perfusion and suggests considering more frequent use of TBA in conjunction with PW/DW imaging, rather than solely as a last-resort treatment measure (38). However, existing research only provides single-group follow-up results for TBA treatment in CV, and there have been no cohort studies in the clinical setting to compare the differences between TBA and standard treatment. The subgroup analysis in this meta-analysis reveals that receiving both IAVI and TBA only prolongs patients’ ICU stay duration and total hospital stay, with no apparent benefit in terms of therapeutic efficacy for CV compared to the standard treatment group. Our research findings did not indicate a beneficial effect of TBA on patients’ prognosis, but it is important to note that this conclusion is based on the results of only two studies. In the future, high-quality, large-scale clinical studies are still needed to provide compelling evidence regarding the effectiveness of TBA in treating CV. It is noteworthy that the combination therapy of IAVI with TBA demonstrated lower efficacy in improving primary outcomes compared to IAVI monotherapy. This discrepancy may be attributed to multiple factors. Firstly, the increased procedural complexity and the risk of complications associated with dual therapy might negate the individual advantages of IAVI and TBA, especially in patients with complex vascular anatomy or severe vasospasm. Secondly, the timing and criteria for selecting patients for combined therapy versus monotherapy could influence treatment outcomes, as those undergoing combined treatment may have more severe or intractable vasospasm, leading to inferior results. Additionally, the variation in technical expertise and procedural practices across different treatment centers could impact the success rates and clinical outcomes of these therapies. Therefore, conducting further research is essential to gain a more accurate understanding of the optimal timing and patient selection for each treatment modality.

Our meta-analysis revealed nuanced outcomes, with no clear differences between endovascular therapy and standard care, highlighting the need for an in-depth analysis. Contributing to this are the diverse patient demographics and the variability in both the severity and timing of CV treatment, which may obscure outcome disparities. The range of endovascular techniques applied, encompassing various devices and procedural nuances, could lead to outcomes that do not decisively favor one treatment approach over another. Additionally, inconsistencies in clinical practices among different treatment centers and the absence of standardized protocols for CV management could lead to uneven results. The timing of the intervention relative to symptom onset also plays a pivotal role; if not optimally aligned within the therapeutic window, it may result in subdued treatment benefits. These aspects highlight the need for meticulous design in future studies to clarify the effects of endovascular therapies on CV, emphasizing the importance of standardized treatment approaches and optimal timing of intervention.

There are several methods used for the prevention of CV caused by aSAH. The widely used “triple-H” therapy, which includes induced hypertension, hypervolemia, and hemodilution, was once commonly employed. However, research failed to demonstrate the benefits of prophylactic triple-H treatment, possibly due to its association with other complications, leading to its current disuse. Presently, oral nimodipine is the only treatment method recommended in guidelines for all aSAH patients. Although it does not improve CV, it has been proven effective in enhancing neurological outcomes. Other prophylactic uses of CCB, corticosteroids, and magnesium sulfate have not shown clinical significance (11, 39). Current guidelines do not recommend prophylactic hypervolemia or TBA before angiographic spasm occurs. Research results on TBA are inconsistent, with some studies indicating a reduced risk of DCI and CV recurrence, but failing to demonstrate clinical benefits (40, 41). Some studies suggest that intraventricular drainage may have application value in preventing CV, especially in reducing the incidence of vasospasm, mortality rate, and the need for endovascular rescue therapy following procedures such as thrombus removal and ventriculostomy (42–44). Overall, prophylactic treatment should still be chosen based on physicians’ experience and treatment center conditions. Postoperative measures such as active blood volume management, monitoring of patients’ neurological status, enhanced imaging review, and continued oral nimodipine administration remain relatively recommended preventive measures. Recent evidences indicate that several diagnostic tools, such as perfusion CT scan, continuous electroencephalography, xenon-CT scan and brain microdialysis and elevated CSF lactate and glucose levels in the first 3 days following aSAH are predictors of subsequent DCI-related neurological impairment (45–48). Further research is still necessary to determine the most effective preventive approaches.

This study encompasses certain limitations that may affect the interpretation of results. Primarily, it includes only 7 studies, each with limited sample sizes, which may not adequately represent the broader patient population, thereby necessitating larger-scale studies for more definitive validation. These studies originate from diverse clinical centers across different countries, introducing potential variability in data source processing and treatment protocols. Moreover, the generally short follow-up period in these studies restricts our ability to comprehensively analyze long-term outcomes post-discharge. Although we endeavored to apply unified evaluation criteria to mitigate the impact of heterogeneity, the variability in treatment approaches, timing, and endovascular techniques used across different centers remains a challenge. Notably, the lack of RCTs addressing this specific condition underscores a significant gap in high-quality evidence. Therefore, future research needs to overcome these limitations to improve the reliability and generalizability of the study.

Endovascular therapy, especially IAVI, is a promising treatment option for reducing in-hospital mortality in patients with CV. However, no significant improvement has been observed in long-term prognosis and functional recovery. Further research with larger sample sizes and randomized controlled trials is necessary to validate the study findings and optimize the treatment strategy for cerebral vasospasm in aSAH patients.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

Y-HM: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. RS: Data curation, Investigation, Methodology, Software, Supervision, Writing – original draft. S-HL: Data curation, Formal analysis, Methodology, Software, Writing – review & editing. TW: Data curation, Formal analysis, Investigation, Methodology, Software, Writing – review & editing. SL: Formal analysis, Investigation, Software, Writing – review & editing. C-WZ: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing.