Compared to large vessel occlusion in the anterior circulation, acute basilar artery occlusion in the posterior circulation has higher mortality and disability rates with drug therapy alone, but there has been a lack of high-level evidence to support the efficacy and safety of posterior circulation thrombolysis. For this reason, the BAOCHE study, a multicenter randomized controlled study from China, has been attracting much attention, and the industry expects it to provide more high-quality clinical findings for clinical work and even guideline development on posterior circulation embolization.

On May 6, 2022, the results of the Basilar Artery Occlusion: Chinese Endovascular Trial (BAOCHE), led by Prof. Dr. Ji, Xunming of Xuanwu Hospital Capital Medical University, with Prof. Dr. Tudor Jovin of Cooper University Medical Center as co-PI, were presented at the European Stroke Conference (ESOC 2022). The BAOCHE study adds high-level clinical evidence for EVT treatment of patients with acute basilar artery occlusion within the 6-24 hour time window, bridging the gap of lack of high-quality studies on posterior circulation embolization, and will have a profound impact on the clinical management of BAO.

Stroke Vision invited Prof. Dr. Ji Xunming, the initiator of the BAOCHE study, and Dr. Li Chuanhui, a key member of the research team, for an interview to discuss the design and findings of the BAOCHE study, as well as the future development of posterior circulation embolization.

Question 1

What was the original intention and purpose of the initiation of the BAOCHE study?

Prof. Dr. Ji, Xunming: In 2015, with the publication of the five major RCT studies on anterior circulation embolization, the guidelines were updated and there is a sufficient evidence-based basis for embolization of anterior circulation large vessel occlusions. Compared to large vessel occlusion in the anterior circulation, acute basilar artery occlusion in the posterior circulation has a higher mortality and disability rate with drug therapy alone, especially in the Asian population. The aim of the BAOCHE study was to investigate the efficacy and safety of embolization in stroke patients with posterior circulation large vessel occlusion through a multicenter RCT.

Question 2

What are the core conclusions obtained from the BAOCHE study, which lasted for almost 7 years?

Prof. Dr. Ji, Xunming: The BAOCHE study has now concluded that in patients with acute basilar artery occlusion with onset/last normal at 6-24h (baseline NIHSS ≥6; infarct size meets inclusion criteria), the application of Solitaire™ intracranial thrombolysis stent thrombolysis benefits patients, with a significantly higher proportion of patients achieving an mRS score of 0-3 at 90 days than in the drug treatment group.

Question 3

What are the main differences in the design of BAOCHE compared to the other two posterior circulation studies - BEST and BASICS - and the reasons for the positive results obtained?

Prof. Dr. Ji, Xunming: The time window for enrolling patients was 8 hours for the BEST study and 6 hours for the BASICS study. The BAOCHE study was designed to include patients with a time window of 6-24 hours, thus complementing the first two RCT studies. Compared with the BEST and BASICS studies, the BAOCHE study applied the pc-ASPECT score and pontocerebral midbrain index to screen and include patients in the study design to accurately guide enrollment, and all included patients were those who underwent rigorous imaging screening and had small posterior circulation supply areas, especially the core brainstem infarct area; the actual enrollment process of BAOCHE had close to 1/3 This made the assessment of posterior circulation infarction more accurate during the enrollment process, which should be an important reason for the positive results of the BAOCHE study. Secondly, the BAOCHE study was conducted with strict protocol implementation and maintained a low cross-group rate, which also led to a positive ITT analysis in the BAOCHE study.

Question 4

With the publication of the results of the BAOCHE study, is it safe to assume that strong evidence has been obtained for the efficacy and safety of thrombolysis for acute occlusion of the basilar artery in the posterior circulation? Is it possible to change the guidelines in the future?

Prof. Dr. Ji, Xunming: Before the results of the BAOCHE study were published, thrombectomy had been used as a routine treatment for acute BAO (basilar artery occlusion) in many centers, but clinicians still had doubts about the exact benefit of thrombectomy for stroke patients with basilar artery occlusion, and the indications were based on the clinical experience of the attending physician. There is a lack of evidence to support the results of high-quality clinical studies.

With the release of the BAOCHE study, clinicians will be more confident in screening patients for acute BAO thrombolysis and in performing thrombolysis. According to the results of the study, aggressive intervention with the Solitaire™ Intracranial Thrombectomy Stent for patients who meet the BAOCHE study entry criteria may provide significant benefits to patients.

BAOCHE is a scientifically designed and rigorously executed high level RCT and should have an impact on future guideline development as the results of subsequent studies are published.

Question 5

In the BAOCHE study, 92.7% of the stents used for thrombolysis were Solitaire™ , why this design?

Prof. Dr. Ji, Xunming: In the 2015 update of the ischemic stroke guidelines, stent retrieval with Solitaire™ received the highest level of recommendation. Therefore, the design of the BAOCHE study also specified that the Solitaire™ intracranial stent, which is the most commonly used and most accepted device by clinicians, should be used for embolization.

In the Chinese population, the percentage of patients with basal occlusion based on intracranial atherosclerotic stenosis is significantly higher compared to the European and American populations. Some patients may require intracranial stenting after mechanical embolization, and the Solitaire™ intracranial embolization stent can be released for stenting, making it ideal for embolization treatment in the Chinese population.

Of course, over the course of the BAOCHE study, there was a lot of evidence-based evidence that aspiration was an effective means of embolization. Overall, the Solitaire™ intracranial stent was used in more than 90% of the patients in the BAOCHE embolization group. Further studies are needed to confirm whether other embolization devices, such as the Trevo stent, or other means of embolization, such as aspiration, still benefit patients and their efficacy compared to the Solitaire™ intracranial embolization stent.

Question 6

The Solitaire™ intracranial stent was involved in five major RCTs that rewrote the guidelines for acute stroke in 2015, recommending stent retrieval therapy at the highest level of "Class I recommendation, Level A evidence". Can you tell us about your understanding of the Solitaire™ stent series from the trial itself and from a clinical perspective?

Prof. Dr. Ji, Xunming: We have been using Solitaire™ intracranial stents for many years, and they are versatile, easy to use, have a short learning curve, and have a guaranteed revascularization rate. The Solitaire™ intracranial stent is now available in more styles and models, providing clinicians with a wide range of options to choose the right stent according to the patient's vascular status and improve the efficiency of revascularization.

Question 7

In your opinion, which patients with acute occlusion of the basilar artery would benefit most from mechanical embolization? For example, the choice of time window, initial NIHSS score, branch compensation, infarct size, etc.?

Prof. Dr. Ji, Xunming: Currently, patients who meet the inclusion criteria of the BAOCHE study can benefit from mechanical embolization. From the specific data of the BAOCHE study, patients with a time window of 6-12 h, NIHSS score of 10-20, pc-ASPECT score of 6-8, and pontocerebral midbrain index of 2 benefited the most from embolization.

Dr. Chuanhui Li: Specifically, according to the subgroup analysis of the BAOCHE study, those with an onset/last normal time window of 6 to 12 hours are more likely to benefit than those with 12 to 24 hours; those with an NIHSS score of 10-20 are more likely to benefit than those with a score of less than 10 or more than 20, for example, for patients with particularly severe symptoms, especially coma, whether embolization or not may have a prognosis is worse. In addition, patients with a pc-ASPECT score of 6-8 and a pontocerebral midbrain index of 2 have been shown in previous studies to benefit most from embolization, as confirmed by the results of the BAOCHE study subgroup analysis. The results of these subgroup analyses are very similar to the results of previous studies.

Question 8

We know that the NIHSS score was 10 in the original design and was changed to greater than or equal to 6 later. Does the positive result of the BAOCHE study also apply to patients with a score below NIHSS 6?

Prof. Dr. Ji, Xunming: The BAOCHE study did not enroll patients with mild disease with NIHSS scores below 6, and there is no evidence to support this. Based on clinical experience, there is a theoretical benefit for patients with progressive stroke, but because there is no clear evidence, bolus retrieval for this group of patients should still be done with caution and further studies are needed.

Question 9

The BAOCHE study provided a rationale for mechanical embolization in BAO patients in the 6-24 hour time window, what about patients in any other time window?

Prof. Dr. Ji, Xunming: The BAOCHE study did not include patients outside the 6-24h time window, so there is no strong evidence to support the same embolization for other patients. From our experience with the BAOCHE study, it is not infeasible to give thrombolysis to patients with other time windows of basilar occlusion, including some other studies that have confirmed the benefit of circulating thrombolysis after the 0-12h time window. For mechanical embolization beyond 24h, future studies are needed to further expand the time window for embolization therapy. I believe that with the continuous improvement of neuroprotective technology and clinical treatment experience, it will be possible to continuously expand the time window of embolization treatment to benefit more patients.

Question 10

Is there anything else that needs to be noted for mechanical embolization in BAO patients, such as how to reduce the bleeding tendency?

Prof. Dr. Ji, Xunming: Through the BAOCHE study, we believe that strict patient screening is an important prerequisite for patients with acute basilar artery occlusion to benefit from thrombolysis, and an important guarantee for reducing postoperative complications.  It is important to promote the homogenization of stroke thrombolysis across the country through rigorous patient assessment and screening on the one hand, and strict and uniform training on the other hand, to improve the medical standard and thus reduce the tendency of bleeding. Stroke, especially posterior circulation stroke, has a high mortality and disability rate, and is difficult to refer because of its condition, which requires the establishment of county-based thrombolysis and retrieval training centers to train more and more independent operators, as well as remote guidance, to effectively improve the treatment of posterior circulation stroke.

Question 11

The study on posterior circulation RCT is a difficult study, what do you think are the most critical factors for the success of the BAOCHE study? What experience and suggestions do you have to share for everyone to conduct high quality RCT bolus retrieval studies in the future?

Prof. Dr. Ji, Xunming: The most critical factor is the scientific design of the study protocol and the strict implementation of the study protocol during the project, as well as the concerted efforts of our team members and the full cooperation of the enrolled centers. The fundamental reason is that there is a lack of evidence to guide the treatment of acute basilar artery occlusion in the posterior circulation, a disease with a poor clinical prognosis, and it is the duty of the physicians to carry out the study because of the real clinical needs.

We currently believe that the key to high-level RCT research is still the IDEA, the selection of the scientific question. Aiming at a clinical pain point, after scientific design of the study and strict implementation of the design plan, we can get the data to answer the pain point problem. In the future, we must focus on the "urgent, difficult, and worrying" problems of the academic community to carry out research, and the research guided by this idea is the most practical value.