Supplementary Material for: Intracranial Stenosis: Impact of Randomized Trials on Treatment Preferences of US Neurologists and Neurointerventionists

Background and Purpose: Medical and endovascular treatment options for stroke prevention in patients with symptomatic intracranial stenosis have evolved over the past several decades, but the impact of 2 major multicenter randomized stroke prevention trials on physician practices has not been studied. We sought to determine changes in US physician treatment choices for patients with intracranial atherosclerotic stenosis (ICAS) following 2 NIH-funded clinical trials that studied medical therapies (antithrombotic agents and risk factor control) and percutaneous transluminal angioplasty and stenting (PTAS). Methods: Anonymous surveys on treatment practices in patients with ICAS were sent to physicians at 3 time points: before publication of the NIH-funded Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial (pre-WASID survey, 2004), 1 year after WASID publication (post-WASID survey, 2006) and 1 year after the publication of the NIH-funded Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial (post-SAMMPRIS survey, 2012). Neurologists were invited to participate in the pre-WASID survey (n = 525). Neurologists and neurointerventionists were invited to participate in the post-WASID (n = 598) and post-SAMMPRIS (n = 2,080) surveys. The 3 surveys were conducted using web-based survey tools delivered by E-mail, and a fax-based response form delivered by E-mail and conventional mail. Data were analyzed using the χ2 test. Results: Before WASID, there was equipoise between warfarin and aspirin for stroke prevention in patients with ICAS. The number of respondents who recommended antiplatelet treatment for ICAS increased across all 3 surveys for both anterior circulation (pre-WASID = 44%, post-WASID = 85%, post-SAMMPRIS = 94%) and posterior circulation (pre-WASID = 36%, post-WASID = 74%, post-SAMMPRIS = 83%). The antiplatelet agent most commonly recommended after WASID was aspirin, but after SAMMPRIS it was the combination of aspirin and clopidogrel. The percentage of neurologists who recommended PTAS in >25% of ICAS patients increased slightly from pre-WASID (8%) to post-WASID surveys (12%), but then decreased again after SAMMPRIS (6%). The percentage of neurointerventionists who recommended PTAS in >25% of ICAS patients decreased from post-WASID (49%) to post-SAMMPRIS surveys (17%). Conclusions: The surveyed US physicians' recommended treatments for ICAS differed over the 3 survey periods, reflecting the results of the 2 NIH-funded clinical trials of ICAS and suggesting that these clinical trials changed practice in the USA.

背景与目的：近数十年来，症状性颅内狭窄患者卒中预防的内科与血管内治疗方案已发生显著演变，但两项大型多中心随机卒中预防试验对临床医师诊疗实践的影响尚未得到研究。本研究旨在明确两项由美国国立卫生研究院（National Institutes of Health, NIH）资助的临床试验——针对内科治疗（抗血栓药物与危险因素控制）及经皮腔内血管成形术和支架置入术（percutaneous transluminal angioplasty and stenting, PTAS）的试验——开展后，美国医师针对颅内动脉粥样硬化性狭窄（intracranial atherosclerotic stenosis, ICAS）患者的治疗选择变化。
方法：本研究通过三个时间点向临床医师发放针对ICAS患者诊疗实践的匿名调查问卷：①美国国立卫生研究院资助的华法林-阿司匹林症状性颅内疾病（Warfarin-Aspirin Symptomatic Intracranial Disease, WASID）试验发表前（2004年，WASID前调查）；②WASID试验发表后1年（2006年，WASID后调查）；③美国国立卫生研究院资助的颅内狭窄患者卒中复发预防的支架置入与强化药物管理（Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis, SAMMPRIS）试验发表后1年（2012年，SAMMPRIS后调查）。WASID前调查仅邀请神经内科医师参与（n=525）；WASID后及SAMMPRIS后调查则同时邀请神经内科医师与神经介入医师参与（分别为n=598与n=2080）。三项调查均通过网络问卷工具以电子邮件形式发放，同时配套提供通过电子邮件与传统邮寄方式送达的传真应答表单。数据采用卡方检验（χ² test）进行分析。
结果：WASID试验发表前，临床医师在使用华法林与阿司匹林预防ICAS患者卒中方面处于均衡状态。针对前循环与后循环ICAS患者，推荐抗血小板治疗的受访者占比在三项调查中均呈上升趋势：前循环分别为WASID前44%、WASID后85%、SAMMPRIS后94%；后循环分别为WASID前36%、WASID后74%、SAMMPRIS后83%。WASID试验发表后，最常推荐的抗血小板药物为阿司匹林；而SAMMPRIS试验发表后，阿司匹林联合氯吡格雷成为最主流的推荐方案。在神经内科医师中，推荐对超过25%的ICAS患者实施PTAS的占比从WASID前的8%小幅升至WASID后的12%，但在SAMMPRIS试验发表后回落至6%。神经介入医师中，推荐对超过25%的ICAS患者实施PTAS的占比则从WASID后的49%降至SAMMPRIS后的17%。
结论：本研究涉及的美国医师针对ICAS的推荐治疗方案在三个调查周期中存在显著差异，这一变化反映了两项美国国立卫生研究院资助的ICAS临床试验的研究结果，同时提示上述临床试验改变了美国的临床诊疗实践。