Discussion

HBC is the use of core platinum coils coated with hydrogel material containing several characteristics that are not available with standard BPC. HBC allows for the absorption of fluid and its subsequent expansion, resulting in higher packing densities.^{Reference Ferral13} While many intracranial aneurysms were occluded with the use of BPC, HBCs are gaining popularity as a potential alternative treatment. However, very limited research has been done to analyze the efficiency and safety profile of HBC. Xue et al.^{Reference Xue, Chen, Lin, Xu, Shen and Wang14} was one of the first groups to systematically evaluate RCTs that aimed to analyze the differences between HBC and BPC.^{Reference Xue, Chen, Lin, Xu, Shen and Wang14} The final version of the manuscript included 4 RCTs, which included 1,526 patients in total (HBC = 767; BPC = 759). Xue et al.^{Reference Xue, Chen, Lin, Xu, Shen and Wang14} also focused on periprocedural events including but not limited to failed procedure, coiled migration and perforation. It was found that HBC had no difference in terms of reducing these events. While it may be argued that this may be subject to physician expertise acting as a confounding variable, similar results to our paper in the post-procedural outcomes were reported. For example, no significant differences were seen in mid-term efficacy outcomes, which included intracranial aneurysm recurrences, complete occlusion and excellent functional outcomes (mRS = 0). Interestingly, HBC patients actually reported significantly better good functional outcomes (mRS = 0–2) post-procedure when compared with their BPC counterparts. Finally, while BPC patients revealed lower rates of recurrence (p = 0.008) and residual aneurysm (p = 0.002), both cohorts showed comparable results in stroke, morbidity and mortality rates. Xue et al.^{Reference Xue, Chen, Lin, Xu, Shen and Wang14} had shown that even though HBC may offer better results in some outcomes, its safety profile and overall efficacy were no different than BPC. A similar systematic review and meta-analysis was conducted 7 years later by Cortese et al.^{Reference Cortese, Ghozy and Zarrintan4} This time, 5 RCTs were included in the final version of the analysis with 2,126 patients (HBC = 1064 and BPC = 1062). In line with our findings, significant differences emerged only when assessing major recurrences (p = 0.03) and residual aneurysms (p = 0.01), both of which favored the HBC cohort. In addition, HBC trended toward better complete occlusion at follow-up, yet the results were still not significant (OR 1.21; 95% CI 0.99–1.48; p = 0.06). That said, after discovering substantial heterogeneity between the included studies (I ² = 54%, p = 0.09), an outlier study was removed. Once the outlier was removed, a significantly higher rate of complete occlusion at the last follow-up was revealed in favor of the HBC group (OR 1.29; 95% CI 1.18–1.42; p = 0.001).

Results from Cortese et al.^{Reference Cortese, Ghozy and Zarrintan4} and Xue et al.^{Reference Xue, Chen, Lin, Xu, Shen and Wang14} helped shape our understanding of HBC’s safety profile and efficacy in treating patients.^{Reference Cortese, Ghozy and Zarrintan4,Reference Xue, Chen, Lin, Xu, Shen and Wang14} However, a key consideration is that these studies analyzed a total of nine RCTS, with four overlapping studies. In other words, only five RCTs comparing HBC to BPC in intracranial aneurysms were conducted and analyzed to this day. Therefore, the generalizability of both of these results remains limited, and further research would help strengthen these findings. Our study helps add to these findings by evaluating a sixth RCT conducted in 2024, adding 432 patients to be analyzed.^{Reference Imamura, Sakai and Sakai9}

Previous non-RCT studies have also evaluated the differences between HBC and BPC in the past. As early as 2006, Gaba et al. compared 50 HBC aneurysms (17 small, 26 medium and 5 large) to 57 BPC aneurysms (29 small, 24 medium and 4 large) and looked to analyze many metrics including volume percentage occlusion (VPO) and length of hospital stay.^{Reference Gaba, Ansari, Roy, Marden, Viana and Malisch15} It was found that HBC yielded higher VPO compared to BPC (p = 0.016). On the other hand, no differences in length of hospital stay were detected. This study also found that although HBC incurred higher initial costs, these were balanced by reduced recurrence rates, something that clinicians may want to consider. This is especially relevant when discussing centers with limited resources. Therefore, it requires careful evaluation from the clinicians on site to judge whether the implementation of HBC for reducing recurrence rates is feasible. In 2014, Lee et al. tested both coiling methods in a single-center experience.^{Reference Lee, Seo and Lee16} This time, 430 and 253 intracranial aneurysms were compared in the HBC and BPC cohorts, respectively. Similar to our findings, the HBC cohort had lower recurrence rate (p < 0.001). The HBC cohort also had lower retreatment rate (p = 0.004) and higher packing density (p < 0.001) compared to the BPC group. Comparable results were observed when MacDonell et al. (2022) contrasted both coiling methods in treating the anterior communicating artery.^{Reference MacDonell, Field and Entezami17} Moreover, when conducting a subanalysis of only ruptured aneurysms, MacDonell et al. (2022) showed significantly lower recurrence rates in the BPC cohorts, suggesting a potential advantage of HBC in the treatment of ruptured aneurysms.

Other studies focused on comparing different generations of HBC. The first-generation hydrogen-based coil included a platinum core with an outer hydrogel coating. Second generations were then developed. These included three main parts: framing, filling and finishing coil. In addition, these coils had an inner hydrogel core with an outer platinum core, allowing it for similar usage and deployment compared to BPC.^{Reference Abi-Aad, Rahme and Patra3,Reference Ferral13} When Abi-Aad et al. (2022) compared both generations to BPC, it was revealed that first-generation HBC offered significantly lower recurrence rates (p = 0.02) (length of follow-up 7.5–18 months).^{Reference Abi-Aad, Rahme and Patra3} Moreover, first-generation HBC offered a packing density of 58.5%, while BPC only offered 24.1% (p < 0.001). Initial occlusion rates trended toward first-generation HBC but were not significant (48.4% HBC vs. 42.9% BPC, p = 0.08). When evaluating second-generation HBC, the authors also revealed significantly lower recurrence rates with HBC (p = 0.007). Additionally, patients treated with second-generation HBC were 28% less likely to experience residual aneurysm neck (p = 0.02) and 58% less likely to obtain retreatment therapy (p = 0.01)

It is essential to acknowledge the rapid progress being made in the development of HBC technologies. Specifically, the ability of hydrogel-based coils to undergo phase transitions in response to physical or chemical stimuli is an area of interest. One of the most recent inventions is a photo-modifiable, shear-thinning liquid embolic that can span multiple embolic categories. This system is mainly composed of HBC material and laser. Once coiling takes place, a microcatheter-like laser probe is shined at the liquid (inside of the aneurysm), rendering it semi-solid. This phase change ensures immediate complete occlusion of the area covered by liquid. It also enables reduction in the liquid escaping the aneurysm before occlusion.

While our study offers deeper understanding of HBC compared to BPC, it is important to recognize some of its limitations. Our study included approximately 2500 patients in total with an almost even split between HBC and BPC cohorts. Although this represents the largest patient cohort among systematic reviews to date, the sample size still limits the generalizability of the findings. Another limitation of this study is the possibility of the presence of confounding variables that may have affected statistical results. For example, the size of aneurysms as well as the neck sizes are variables that differ from one study to the other. These variations may act as confounding variables on the outcomes of HBC and BPC patients in the studies. Previous literature has shown that larger aneurysms and neck have been associated with worse outcomes.^{Reference Fukuda, Hyohdoh and Kawada18–Reference Futami, Misaki, Uno, Kamide and Nakada20} Additionally, while HBC is considered to be revolutionary in the field of interventional treatment, first-generation hydrogen-based coils were considered stiff, had limited versatility and were difficult to deploy and reposition. Therefore, centers with limited resources and without access to second-generation HBC should interpret our findings, as well as those from previous studies, with diligence. Challenges encountered by clinicians using first-generation HBC may lead to poorer outcomes, including higher complication, recurrence and retreatment rates compared with standard BPC. A subgroup analysis comparing first-generation to second-generation hydrogel coils was to be included in this study due to its value in helping us understand our results. It may assist in understanding more clearly whether the observed advantages differ between hydrogel coil generations. However, due to the unavailability of data in the included studies comparing hydrogel coil generations to BPC, this objective was aborted.