Comparative Effectiveness of Carotid Artery Revascularization vs Medical Therapy

描述（由申请人提供）：随机对照试验（RCTs）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）在预防卒中方面优于药物治疗。然而，虽然大多数接受颈动脉血运重建术的患者接受了无症状疾病的治疗，但无症状疾病患者的血运重建术的益处相当有限。此外，临床试验大约始于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，对这种血管疾病的医学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）在治疗无症状颈动脉狭窄中越来越受青睐。虽然最近的试验只关注CEA与CAS的比较，但与医学管理的颈动脉狭窄相关的卒中发生率下降导致许多人质疑血运重建术是否优于积极的血管危险因素控制。三组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，不能提供长时间的答案，并且可能只招募通常在随机对照试验中研究的最健康的患者子集。自从第一项RCT发表证明CEA优于药物治疗以来，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重现。为了解决关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）的持续争论，我们建议在一项6000例患者的回顾性队列研究中，使用合并的退伍军人健康管理局和医疗保险数据，检查初始药物治疗与早期颈动脉干预的比较有效性。我们将特别比较每种血运重建策略与药物治疗，并检查一些关键变量（如年龄，房颤的存在）对干预与药物治疗比较有效性的影响。我们将使用先进的统计技术来克服医学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名医学管理患者、1500名接受CEA的患者和1325名接受CAS的患者的30天和5年结局。我们的首要假设是，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.