Our analysis, which included data from 7 RCTs and 2419 patients, demonstrated that the aggregate efficacy outcome of stroke during the non-periprocedural stroke did not differ significantly between STA-MCA bypass and BMT groups. ICAO stroke, the ravages of atherosclerosis [14, 15], accounts for 15% of all strokes, and the rate of ipsilateral stroke is 2.1~3.8% per year due to non-selective carotid artery occlusion in the USA. The mechanisms include downstream embolus production and residual embolism, among which cortical artery compensation after carotid artery occlusion may determine the recurrence of stroke . Clinical symptoms of this kind of stroke are regularly associated with intracranial emboli in the distal carotid or middle cerebral arteries.
The extracranial section of the internal carotid artery occlusion (ICAO) was handled by surgical way for extracranial-intracranial vascular bypass, striding the lesion area, and improving distal vascular blood flow to reduce the risk of stroke and enhance local brain nerve function. In 1967, Yasargil performed the first procedure for a patient with middle cerebral artery (MCA) occlusion of Marfan’s syndrome. In 1985, Sundt et al.  retrospectively analyzed 415 cases of ischemic cerebrovascular patients undergoing STA-MCA bypass surgery in 8 years, showing the patency rate reached 99%, which was confirmed by digital subtraction angiography and transcranial Doppler. This series of retrospective studies strongly demonstrated the safety and efficacy of this procedure. This research continues to languish. However, considering that for a specific patient, Schmiedek et al.  thought ICAO does not always result in cerebral hemodynamic disorder due to the existence of compensatory mechanisms such as collateral circulation. It has become a key issue in relevant studies to evaluate the hemodynamic status of the patient and as one of the indications for intervention. In order to certify the above opinion, the team of Grubb et al.  conducted a prospective blind longitudinal cohort study, indicating that the incidence rate of all stroke in patients with oxygen extraction fraction (OEF) elevation was higher than that in patients with normal OEF, and the relative risk of all stroke and ipsilateral stroke caused by OEF elevation was 6.0 and 7.3, respectively, meaning that symptomatic ICAO of the extracranial segment is associated with a higher risk of subsequent ischemic stroke, particularly in patients with elevated OEF. For high-risk patients, extracranial-intracranial (EC-IC) bypass surgery could theoretically benefit from vascular bypass technology, since it reduces the percentage of OEF to normal levels.
When designing the Carotid Occlusion Surgery Study (COSS) study scheme, 40% of the incidence of stroke in the drug group was set according to previous studies, and the improvement of drug treatment resulted in a significant reduction of the incidence of stroke, resulting in the deviation of the original study scheme. COSS funded by the National Institutes of Health (NIH), showing 40% of the incidence of stroke in the drug group, was set according to previous studies. However, the improvement of drug treatment resulted in a significant reduction of the incidence of stroke, which led to the deviation of the original study scheme and the failure of COSS study. And this is the reason why we did not include this study in our discussion. Therefore, we conducted a subgroup analysis according to literature impact factor. In terms of relatively high-quality literature (IF> 5), there was no heterogeneity between STA-MCA bypass and BMT groups (I2 = 28%, P = .24). The random effect model was adopted to analyze and test for overall effect, Z = .29 (P = .77), manifesting that there was no significant difference between STA-MCA bypass and BMT in symptomatic ICAO. As for relatively poor-quality literature (IF < 5), heterogeneity existing between STA-MCA bypass, and BMT groups (I2 = 50%, P = .13), the random effect model was adopted to analyze and test for overall effect (Z = .72 (P = .47)) proving the same conclusion. In the aspect of the design of the test scheme of COSS, the patients with the highest potential risk of ischemia fail to be screened out due to the inclusion time of patients [19, 20] and the inclusion criteria of PET examination .
Some surgeons with 2-day training or less than 10 bypass surgeries were also admitted to the COSS, which may lead to an abnormal increase in the incidence of perioperative adverse events. To reduce the impact of surgical techniques on recurrent stroke and the effects of anesthesia, perioperative intensive care, and nursing strategies in our meta-analysis, we also carried out subgroup analysis with literature from the last decade. No obvious heterogeneity between the two groups (I2 = 28%, P = .24). Overall effect (Z = .61 (P = .54)) also pointed out that STA-MCA bypass was not superior to BMT in symptomatic ICAO.
Chronic hypoperfusion may generate plenty of adverse effects such as brain softening, decreased number of neurons, reduced brain volume, language impairment, and decreased cognitive function [22, 23]. A great part of previous clinical trials had focused only on severe stroke as the endpoint event but had failed to give equal weight to the life outcomes of long-term hypoperfusion or recurrent ischemic events. As far as our team is concerned, several possible reasons may be responsible for this phenomenon. First, although many clinical trials have been done using surgical techniques that were very sophisticated at the time, the technique of bypass surgery was still limited by the surgical capabilities of the surgeons and surgical facilities. Secondly, included clinical trials of EC-IC bypass did not distinguish end-to-end or end-to-side anastomosis. If end-to-side anastomosis is used, there is still a possibility of occlusion of the distal thrombus and abscission to the intracranial. Finally, previous studies did not analyze hemodynamic damage after bypass as an independent risk factor. As to whether such patients can benefit from bypass surgery, subsequent studies should not only devote to the recurrence rate of stroke in the short and long term, but also take other factors closely related to patients’ quality of life, such as cognitive function, as important indicators.
To sum up, our results are subject to the limitations inherent to meta-analyses involving the pooling of data from different trials with different study protocols, definitions of clinical outcomes, and baseline characteristics of patients. New multicenter randomized controlled studies will be conducted in evaluation of patients’ cerebral hemodynamic status, establishing accurate indicators of illness and efficacy as the endpoint and perfecting detailed inclusion criteria to improve the study protocol. Our meta-analysis has several advantageous features, including a greater number of patients and restriction to only large RCTs that are less likely to be subject to publication bias.