Comparative Effectiveness of Carotid Artery Revascularization vs Medical Therapy

描述（由申请人提供）：随机对照试验（RCT）已经证实，颈动脉内膜切除术（CEA）在预防无症状和有症状颈动脉狭窄患者卒中方面上级药物治疗。然而，虽然大多数接受颈动脉血运重建的患者接受无症状疾病的治疗，但无症状疾病患者的血运重建获益相当有限。此外，临床试验开始于大约20年前，在此期间，由于新的药理学进展，如高效他汀类药物，改善的抗血小板方案，以及更好地控制高血压，高脂血症和糖尿病，这种血管疾病的药物治疗有了很大的改善。同时，随着CEA手术并发症发生率的降低，颈动脉支架植入术（CAS）在无症状颈动脉狭窄的治疗中越来越受欢迎。虽然最近的试验只集中在比较CEA和CAS，但与医学管理的颈动脉狭窄相关的卒中率下降导致许多人质疑血运重建术是否上级积极的血管风险因素控制。一个三臂随机对照试验可以回答这个问题，但这样的研究将是非常昂贵的，在很长一段时间内不能提供答案，并且可能只招募最健康的患者的子集通常在随机对照试验中研究。自从发表了第一个证明CEA优于药物治疗的RCT以来，人们一直担心试验中观察到的适度获益可能无法在社区中重现。为了解决无症状颈动脉狭窄患者中CEA是否仍上级于药物治疗以及CAS是否上级于药物治疗的持续争论（从未在RCT中进行过评估），我们建议使用合并的退伍军人健康管理局和医疗保险对6000名患者进行回顾性队列研究，以检查初始药物治疗与早期颈动脉干预的比较有效性数据我们将专门将每种血运重建策略与药物治疗进行比较，并检查许多关键变量（例如年龄、是否存在房颤）对干预与药物治疗相比的相对有效性的影响。我们将使用先进的统计技术来克服药物治疗和干预队列中观察到的和未观察到的差异。我们将比较2005年至2008年入组的3175例药物治疗患者、1500例接受CEA治疗的患者和1325例接受CAS治疗的患者的30天和5年结局。我们的总体假设是，药物治疗已经改善到一定程度，只有某些亚组的患者可能受益于血运重建，对许多患者来说，药物治疗可能是首选的治疗策略。

DESCRIPTION (provided by applicant): Randomized controlled trials (RCTs) have established that carotid endarterectomy (CEA) is superior to medical therapy in preventing stroke in both asymptomatic and symptomatic patients with carotid stenosis. However, while the majority of patients who undergo carotid revascularization receive treatment for asymptomatic disease, the benefit of revascularization for patients with asymptomatic disease is quite modest. In addition, the clinical trials were initiated about 20 years ago, and in the intervening period, medical therapy has greatly improved for this vascular disease due to new pharmacological advances such as high potency statins, improved antiplatelet regimens, and better control of hypertension, hyperlipidemia and diabetes. In parallel, as the surgical complication rate for CEA has decreased, the use of carotid artery stenting (CAS) has been gaining favor in the treatment of asymptomatic carotid stenosis. While recent trials have focused exclusively on comparing CEA to CAS, the declining stroke rate associated with medically managed carotid stenosis has led many to question whether either revascularization procedure is superior to aggressive vascular risk factor control. A three-arm RCT could answer this question, but such a study would be very expensive, not provide answers for a long time, and might only enroll the subset of healthiest patients typically studied in an RCT. Since the first RCT was published that demonstrated the superiority of CEA compared to medical therapy there has been a concern that the modest benefit observed in the trials may not be reproducible in the community. To address the ongoing debate of whether among patients with asymptomatic carotid stenosis, CEA is still superior to medical therapy and whether CAS is superior to medical therapy (which has never been evaluated in an RCT), we propose to examine the comparative effectiveness of initial medical therapy compared to early carotid intervention in a retrospective cohort study of 6000 patients using merged Veteran's Health Administration and Medicare data. We will specifically compare each revascularization strategy to medical therapy and also examine the impact of a number of key variables (e.g. age, presence of atrial fibrillation) on the comparative effectiveness of intervention compared to medical therapy. We will use advanced statistical techniques to overcome observed and unobserved differences in the medical therapy and intervention cohorts. We will compare the 30-day and 5 year outcomes of 3175 patients managed medically, 1500 patients who received CEA, and 1325 patients who received CAS entering the cohort from 2005 to 2008. Our overarching hypothesis is that medical therapy has improved to a degree that only certain subgroups of patients may benefit from revascularization and that for many patients medical therapy may be the preferred treatment strategy.