Comparative Effectiveness of Carotid Artery Revascularization vs Medical Therapy

描述(申请人提供)：随机对照试验(RCT)已经证实，在无症状和有症状的颈动脉狭窄患者中，颈动脉内膜切除术(CEA)在预防中风方面优于药物治疗。然而，虽然大多数接受颈动脉血管重建术的患者都接受了无症状疾病的治疗，但对于无症状疾病的患者来说，血管重建术的益处相当有限。此外，临床试验是在大约20年前开始的，在此期间，由于高效他汀类药物、改进的抗血小板方案以及更好地控制高血压、高脂血症和糖尿病等新的药理进展，这种血管疾病的医学治疗得到了极大的改善。与此同时，随着CEA手术并发症发生率的降低，颈动脉支架置入术(CAS)在治疗无症状颈动脉狭窄中得到了越来越多的青睐。虽然最近的试验只专注于比较CEA和CAS，但与医学管理的颈动脉狭窄相关的中风发生率的下降导致许多人质疑，这两种血管重建手术是否都优于积极的血管危险因素控制。三臂随机对照试验可以回答这个问题，但这样的研究将非常昂贵，在很长一段时间内不能提供答案，而且可能只招募通常在随机对照试验中研究的最健康患者的子集。自从第一次随机对照试验的发表证明了CEA相对于药物治疗的优越性以来，人们一直担心在试验中观察到的适度益处可能无法在社区中复制。对于在无症状颈动脉狭窄患者中，CEA是否仍然优于药物治疗以及CAS是否优于药物治疗(从未在随机对照试验中进行评估)这一持续不断的争论，我们建议使用合并的退伍军人健康管理局和联邦医疗保险数据对6000名患者进行回顾性队列研究，以检验初始药物治疗与早期颈动脉干预的比较有效性。我们将具体地将每种血运重建策略与药物治疗进行比较，并检查一些关键变量(例如，年龄、是否存在心房颤动)对介入治疗与药物治疗的比较效果的影响。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年进入队列的3175名接受内科治疗的患者、1500名接受CEA治疗的患者和第1325名接受CAS治疗的患者的30天和5年结果。我们的主要假设是，医学治疗已经提高到了一定程度，只有某些亚组的患者才能从血管重建术中受益，而对于许多患者来说，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.