Therapeutic strategies for acute basilar-artery occlusion

To the Editor: Acute basilar-artery occlusion (aBAO) is one of the most severe forms of stroke, with an incidence of severe disability and death of up to 80%.[1–3] Although several previous prospective multicenter randomized controlled trials (RCTs) involving patients with acute stroke due to large-artery occlusion in the anterior circulation have shown that endovascular thrombectomy (EVT) dramatically improves prognosis over best medical management (BMM),[4,5] the efficacy and safety of EVT for aBAO remain controversial. To date, neither of the two RCTs published has shown an overwhelming advantage of EVT over BMM for patients with aBAO.[6,7] The Basilar Artery Occlusion Endovascular Intervention versus Standard Medical Treatment trial was terminated early due to poor recruitment and high crossover.[6] Although EVT showed better efficacy compared with BMM in both per-protocol (44% vs 25%; adjusted odds ratio, 2.9; 95% confidence interval [CI], 1.20–7.03) and as-treated (47% vs 24%; adjusted odds ratio, 3.02; 95% CI, 1.31–7.00) populations, there were no differences in the intention-to-treat analysis (42% vs 32%; adjusted odds ratio, 1.74; 95% CI, 0.81–3.74). Similarly, the Basilar Artery International Cooperation Study (BASICS) trial did not indicate any significant differences between EVT and BMM (44% vs 38%; risk ratio [RR], 1.18; 95% CI, 0.92–1.50).[7] Only a subgroup analysis in which patients’ National Institutes of Health Stroke Scale (NIHSS) score was required to be 10 or above revealed that EVT might provide better results. The long duration (2011–2019), slow enrollment, underlying selection bias (29.2% of eligible patients were treated outside the trial) of the trial and imbalance of patients with atrial fibrillation in the two treatment groups limited some analyses of the BASICS. However, two real-world cohort studies from China indicated that receiving EVT in 24 hours led to better functional outcomes at 90 days than BMM for patients with aBAO.[1,3] Therefore, more well-designed RCTs are necessary to compare the efficacy of EVT and BMM on basilar-artery stroke. Two RCTs in China recently published in the New England Journal of Medicine provide new evidence for the endovascular treatment of aBAO.[8,9] The Endovascular Treatment for Acute Basilar-Artery Occlusion (ATTENTION) trial enrolled 340 patients from 36 centers in China within 12 hours after the estimated time of aBAO from 2021 to 2022 and randomly assigned them into two groups: 226 (31% received thrombolysis) to the EVT group and 114 (34% received thrombolysis) to the BMM group.[8] All patients had a baseline NIHSS score of 10 or higher. Good functional status (modified Rankin scale score, 0–3) at 90 days was observed in 46% of the patients in the EVT group and 23% in the BMM group (adjusted rate ratio [aRR], 2.06; 95% CI, 1.46–2.91). The incidence of symptomatic intracranial hemorrhage was 5% and 0% in the EVT and BMM groups, respectively. The mortality at 90 days in these two groups were 37% and 55%, respectively (aRR, 0.66; 95% CI, 0.52–0.82). In the Basilar Artery Occlusion Chinese Endovascular (BAOCHE) trial, a total of 217 patients from multiple centers in China underwent randomization from 2016 to 2021.[9] Enrollment was terminated at a prespecified interim analysis due to marked differences in the primary outcomes between the two groups. Ultimately, 110 patients were assigned to the EVT group (14% received thrombolysis) and 107 patients to the BMM group (21% received thrombolysis). All patients had a baseline NIHSS score of 6 or higher. Good functional status (modified Rankin scale score, 0–3) at 90 days showed that EVT was significantly superior to BMM (46% vs 24%; aRR, 1.81; 95% CI, 1.26–2.60). The incidence of symptomatic intracranial hemorrhage in the EVT and BMM groups was 6% and 1%, respectively (RR, 5.18; 95% CI, 0.64–42.18). The mortality at 90 days was 31% in the EVT group and 42% in the BMM group (aRR, 0.75; 95% CI, 0.54–1.04). Compared with previous trials, possible reasons for the positive outcomes of the ATTENTION and BAOCHE trials are that: (1) Both trials were strictly conducted, which kept the crossover rate low (5/217 for BAOCHE, 6/340 for ATTENTION). (2) The inclusion criteria of both trials were even more stringent. Patients were eligible for the enrollment of ATTENTION only when their NIHSS was 10 or higher. Both trials required the posterior circulation Alberta Stroke Program Early Computed Tomography Score to be 6 or higher; the BAOCHE trial restricted enrollment to patients with a Pons-Midbrain Index of more than 2 points, to exclude those with large infarcts in the posterior circulation, particularly in the brain stem. What’s more, both trials extended the time window of aBAO (the time window for Basilar Artery Occlusion Endovascular Intervention versus Standard Medical Treatment and BASICS was 0-6 hours), providing evidence that allowed more patients to be treated with EVT. The two trials also had several drawbacks: First, the enrolled populations were all East Asian, with a high prevalence of large-artery atherosclerosis stenosis (44% in ATTENTION), leading to high rates of intracranial angioplasty or stenting. Therefore, caution should be exercised in generalizing these findings to a larger population. Second, the limited proportion of patients who received thrombolysis (32% in ATTENTION and 18% in BAOCHE) owing to a variety of reasons might have influenced the outcomes in the control group. In a prespecified subgroup analysis of 108 patients who received thrombolysis in ATTENTION, no significant differences in the favorable outcomes were observed between the two treatments (RR, 1.57; 95% CI, 0.97–2.54). Third, neither trials included patients with mild stroke (NIHSS < 6), for whom EVT should be carefully considered. Despite these limitations, ATTENTION and BAOCHE were the first to demonstrate the efficacy of endovascular thrombectomy in the treatment of posterior circulation large-vessel occlusion on a global scale, and provided new strategies for the management of severe stroke in the posterior circulation. In recent years, Chinese neurointerventionalists have published several high-quality RCTs in major international journals such as The New England Journal of Medicine, LANCET, and The Journal of the American Medical Association, despite their extremely heavy clinical workload. Their scientific efforts are to be commended for guiding health policy and clinical practice in China, and also for influencing the treatment of stroke in Western countries. Acknowledgments None. Author contributions MG, PY, and JL designed, wrote and edited the manuscript. JL was the corresponding author. All authors approved the final version of the manuscript. Financial support None. Conflicts of interest The authors declare that they have no conflicts of interest.