Medical management with interventional therapy versus medical management alone for unruptu red brain arteriovenous malformations (ARUBA): final follow-up of a multicentre, non-blinded, randomised controlled trial
Medical management with interventional therapy versus medical management alone for unruptu red brain arteriovenous malformations (ARUBA): final follow-up of a multicentre, non-blinded, randomised controlled trial
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DOI：
10.1016/s1474-4422(20)30181-2
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发表时间：
2020-07-01
期刊：
影响因子：
48
通讯作者：
Moskowitz, Alan J.
中科院分区：
文献类型：
--
作者：
Mohr, Jay P.;Overbey, Jessica R.;Moskowitz, Alan J.
在一项关于未破裂脑动静脉畸形（ARUBA）的随机试验中，在一项预先规定的中期分析显示，在预防症状性卒中或死亡方面，单独的药物治疗上级药物治疗和介入治疗的联合治疗后，平均随访33.3个月时停止了随机化。我们的目的是研究这些差异是否持续通过5年的follow-up.Methods ARUBA是一个非盲，随机试验在39个临床中心在9个国家。诊断为未破裂脑动静脉畸形的成年人（岁），从未接受过介入治疗，并且参与的临床中心认为适合进行干预以根除病变，有资格入选。患者通过基于网络的数据收集系统随机分配（1：1），按临床中心分层，采用随机排列区组设计，区组大小为2、4和6，接受单独的医学管理或联合介入治疗（神经外科手术、栓塞或立体定向放射治疗，单独或以任何组合、顺序或编号）。尽管特定中心的患者和研究者不对治疗分配设盲，但其他中心的研究者和临床协调中心的研究者未被告知任何中心的分配或结局。主要结局是至死亡或经影像学证实的症状性卒中的时间，由不参与者护理管理的每个中心的神经科医生评估，并由独立委员会使用适应性方法进行中期分析进行监测。2007年4月4日开始围手术期，2013年4月15日停止，之后随访持续至2015年7月15日。所有的分析都是通过意向治疗进行的。这项试验在ClinicalTrials.gov注册，NCT 00389181。结果在筛选的1740名患者中，226名被随机分配到单独的药物管理（n=110）或药物管理加介入治疗（n=116）。平均随访50.4个月（SD 22.9），死亡或症状性卒中的发生率在单独药物治疗时较低（15/110，3.39/100患者-年）比药物管理和介入治疗（41/116，12.32/100患者-年;风险比0.31，95% CI 0.17 - 0.56）。随访期间，医疗管理组2例患者和介入治疗组4例患者（2例归因于干预）死亡。与介入治疗相比，药物治疗组患者的不良事件发生率较低（283 vs 369; 58.97 vs 78.73每100患者年;风险差异-19.76，95%CI-30.33至-9.19）。解释在延长随访后，ARUBA表明，在预防未破裂脑动静脉畸形患者的死亡或症状性卒中方面，单纯药物治疗仍优于介入治疗上级。关于结果差异的数据应该影响标准的专家实践和向患者提供的信息。两种治疗方法之间的长期风险和差异仍然不确定。
Background In A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA), randomisation was halted at a mean follow-up of 33.3 months after a prespecified interim analysis showed that medical management alone was superior to the combination of medical management and interventional therapy in preventing symptomatic stroke or death. We aimed to study whether these differences persisted through 5-years' follow-up.Methods ARUBA was a non-blinded, randomised trial done at 39 clinical centres in nine countries. Adults (age years) diagnosed with an unruptured brain arteriovenous malformation, who had never undergone interventional therapy, and were considered by participating clinical centres to be suitable for intervention to eradicate the lesion, were eligible for inclusion. Patients were randomly assigned (1:1) by a web-based data collection system, stratified by clinical centre in a random permuted block design with block sizes of two, four, and six, to medical management alone or with interventional therapy (neurosurgery, embolisation, or stereotactic radiotherapy, alone or in any combination, sequence, or number). Although patients and investigators at a given centre were not masked to treatment assignment, investigators at other centres and those in the clinical coordinating centre were not informed of assignment or outcomes at any of the centres. The primary outcome was time to death or symptomatic stroke confirmed by imaging, assessed by a neurologist at each centre not involved in the management of participants' care, and monitored by an independent committee using an adaptive approach with interim analyses. Enrolment began on April 4, 2007, and was halted on April 15, 2013, after which follow-up continued until July 15, 2015. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00389181.Findings Of 1740 patients screened, 226 were randomly assigned to medical management alone (n=110) or medical management plus interventional therapy (n=116). During a mean follow-up of 50.4 months (SD 22.9), the incidence of death or symptomatic stroke was lower with medical management alone (15 of 110, 3.39 per 100 patient-years) than with medical management with interventional therapy (41 of 116, 12.32 per 100 patient-years; hazard ratio 0.31, 95% CI 0.17 to 0.56). Two patients in the medical management group and four in the interventional therapy group (two attributed to intervention) died during follow-up. Adverse events were observed less often in patients allocated to medical management compared with interventional therapy (283 vs 369; 58.97 vs 78.73 per 100 patient-years; risk difference -19.76, 95% CI -30.33 to -9.19).Interpretation After extended follow-up, ARUBA showed that medical management alone remained superior to interventional therapy for the prevention of death or symptomatic stroke in patients with an unruptured brain arteriovenous malformation. The data concerning the disparity in outcomes should affect standard specialist practice and the information presented to patients. The even longer-term risks and differences between the two therapeutic approaches remains uncertain.