The Screening Strategy And Long-term Prognosis Of Endovascular Therapy For Acute Basilar Artery Occlusion

Since the end of 2014,five randomized clinical trials have confirmed the effectiveness and safety of endovascular therapy（EVT）within 6 hours of onset in acute large vessel occlusion of anterior circulation.In 2018,DAWN and DEFUSE-3 trials further demonstrated that patients who meet the imaging criteria within 6-24 hours could benefit from EVT.Therefore,if patients with ischemic stroke are present beyond the time window,it is recommended to select patients for EVT based on their brain tissue imaging（i.e.tissue window）.Several observational studies have shown that EVT significantly improved the rate of recanalization and increased the proportion of functional independence in patients with acute BAO,but the reported rates of functional independence were quite different,ranging from 27.4%to 51.8%.This may because that there are many unsolved problems for EVT in acute BAO.For example,posterior circulation has better collaterals than anterior circulation,and whether is the treatment time window of EVT for acute BAO different from anterior circulation?What imaging criteria should patients meet to benefit from EVT with minimal injury?Also,how is the long-term prognosis of EVT relative to standard medical therapy for acute BAO?These problems are the key factors perplexing decision-making,and are also important factors associated with prognosis of EVT.We explored in depth the time window,tissue window and long-term prognosis of EVT in patients with acute BAO using a nationwide database.Part 1 Association Between Time to Endovascular Therapy and Outcomes in Patients with Acute Basilar Artery OcclusionBackground and purpose:Earlier treatment is significantly associated with better clinical outcomes in acute large vessel occlusion of anterior circulation.However,the relationship between treatment time and clinical outcomes for patients with acute BAO is still unclear.This study aimed to explore whether treatment time modified the efficacy of endovascular treatment（EVT）relative to medical therapy,and assess how and to what extent the treatment time affects the clinical outcomes of EVT in patients with acute BAO.Methods:The EVT for Acute Basilar Artery Occlusion study（BASILAR）was a nationwide registry,which prospectively enrolled consecutive patients with acute BAO within24h of symptom onset between January 2014 and May 2019 in China.Patients were divided into two groups based on the treatment they received:either standard medical therapy alone or standard medical therapy plus EVT（EVT group）.The primary outcome was favorable functional outcome（defined as modified Rankin Scale score[m RS]0-3）at 90 days.Secondary outcomes included functional independence,mortality and symptomatic intracerebral hemorrhage.The treatment effect changing with onset-to-treatment time were determined by adding the onset-to-treatment time and its interaction term with treatment into the model.The associations between onset-to-puncture time（OPT）and outcomes were evaluated using binary logistic regression and restricted cubic spline regression.Results:There were 126 patients receiving standard medical therapy and 461 patients receiving EVT within 6 hours of onset,but 56 cases and 186 cases respectively after 6 hours of onset.The EVT group had higher rates of 90-day favorable outcomes and functional independence but lower mortality than standard medical treatment both within 6 hours and after 6 hours of onset.However,the EVT group had higher risks of symptomatic intracranial hemorrhage.In patients receiving EVT,restricted cubic spline analysis showed that the OPT had L-shaped associations with favorable outcome(P_nonlinearity=0.028)and functional independence(P_nonlinearity=0.025),with the change point around 9 hours of OPT.The benefit of EVT decreased significantly with treatment delay within 9 hours of OPT,but then tended to be stable.Mortality increased significantly with treatment delay within 9 hours of OPT,but then remained stable(P_nonlinearity=0.042).Within the 9-hour time frame,each hour delay from stroke onset to EVT start resulted in a 2.3%decreased probability of favorable outcomes,a2.3%decreased probability of functional independence,and a 2.0%increased probability of mortality.The odds of symptomatic intracerebral hemorrhage did not significantly change with longer delay to EVT.Conclusions:Among patients with acute BAO in routine practice,EVT might be prior to standard medical therapy alone in efficacy and safety both within 6 hours and after 6 hours of onset.For patients treated with EVT,earlier treatment was associated with better prognosis.But the benefit of EVT may sustain stable after 9 hours of onset if patients were properly selected.These results need to be validated in clinical trials or meta-analyses with a larger sample size of patients with acute basilar artery occlusion.Part 2: Effects of Posterior Circulation Acute Stroke Prognosis Early CT Score on Treatment Decision and Clinical Prognosis of Acute Basilar Artery OcclusionBackground and purpose: Several prospective studies have shown that endovascular treatment（EVT）could significantly improve the functional outcomes of patients with acute basilar artery occlusion（BAO）.Nevertheless,these studies did not establish imaging criteria to identify patients most likely to benefit from EVT.The posterior circulation Acute Stroke Prognosis Early Computed Tomography Score（pc-ASPECTS）is a semi-quantitative method for grading irreversible ischemia.This study was sought to examine the safety and efficacy of EVT compared with medical treatment alone according to pc-ASPECTS.Methods: Patients with baseline pc-ASPECTS in the BASILAR（EVT for Acute Basilar Artery Occlusion study）registry were included in this analysis.They were divided into two groups based on the initial treatment intent: standard medical therapy alone（SMT group）or SMT plus EVT（EVT group）.The primary outcome was favorable functional outcome at 90 days.Secondary outcomes included functional independence,mortality and symptomatic intracerebral hemorrhage.The EVT treatment effect modification according to pc-ASPECTS were assessed using Poisson or binary logistic regression models.The associations between baseline pc-ASPECTS and treatment time with prognosis after EVT were also assessed.Results: A total of 823 patients were included.The median（interquartile range,IQR）age,NIHSS score and pc-ASPECTS for the cohort were 65（57-74）years,26（16-33）and 8（7-9）,respectively.Among them,there were 468 patients with pc-ASPECTS 8-10（SMT: 71;EVT: 397）,317 patients with pc-ASPECTS 5-7（SMT: 85;EVT: 232）,and 38 patients with pc-ASPECTS 0-4（SMT: 13;EVT: 25）.Compared with the SMT,EVT was associated with higher rates of favorable outcomes（adjusted RR with 95% CI,4.35 [1.30-14.48] and 3.20 [1.68-6.09];respectively）but lower mortality（60.8% vs 77.6%,P = 0.005 and 35.0% vs 66.2%,P < 0.001;respectively）in the pc-ASPECTS 5-7 and 8-10 subgroups.Continuous benefit curves also showed the superior efficacy and safety of EVT over SMT in patients with pc-ASPECTS ≥ 5.In patients treated with EVT,the effect of onset-to-puncture time on favorable outcome was not significant after adjustment for baseline pc-ASPECTS（adjusted OR,0.98;95% CI,0.94-1.02）.Conclusions: Patients of acute BAO with pc-ASPECTS ≥ 5 could benefit from EVT.The baseline pc-ASPECTS appears more important for decision-making and predicting prognosis than time from onset to EVT.These findings need to be confirmed by studies or randomized trials with a larger sample size in future.Part 3 One-Year Outcome After Endovascular Treatment for Acute Basilar Artery OcclusionBackground and Purpose: The BASILAR study has shown that the endovascular therapy improves outcomes at 90 days than standard medical therapy in patients with acute BAO.However,whether the observed benefit is sustained in the long term remains unknown.We reported the results of 1-year follow-up among patients in the BASILAR registry.Methods: Patients of acute BAO within 24 h of symptom onset were divided into the standard medical therapy alone group or standard medical therapy combined with endovascular therapy group（EVT group）according to the treatment they received.The primary outcome was the score of modified Rankin Scale at one year,assessed using ordinal logistic regression analysis.Secondary outcomes included the favorable outcome,functional independence,excellent outcome and all-cause death,assessed using binary logistic regression analysis.Results: In the BASILAR registry,44 patients were lost to follow up at one-year and 785 patients（94.7%）were included in this analysis.The median of age was 65 years,73.6% were men,and the median baseline NIHSS was 27.The distribution of outcomes on the modified Rankin Scale favored EVT over standard medical therapy（adjusted common odds ratio,4.50;95% CI,2.81 to 7.29;P < 0.001）.Patients in the EVT group had higher proportions of favorable outcome（35.6% vs 11.8%;adjusted odds ratio,4.54 [2.61-8.28],P <0.001）,functional independence（30.9% vs 10.0%;adjusted odds ratio,4.15 [2.32-7.83],P < 0.001）,and excellent outcome（22.6% vs 7.6%;adjusted odds ratio,3.21 [1.69-6.56],P < 0.001）at 1-year.In addition,the cumulative one-year mortality rate was 54.6% in the EVT group versus 83.5% in the standard medical therapy group（adjusted odds ratio,4.36;95% CI,2.69 to 7.29;P < 0.001）.Conclusions: EVT administered within 24 hours of onset is also associated with better functional outcomes and reduced mortality at 1 year follow-up in patients with acute basilar artery occlusion,indicating sustained benefit of EVT.This result needs to be verified by a meta-analysis or clinical trial with a larger sample size of patients with acute basilar artery occlusion.