肾脏支架置入与单纯药物治疗相比无增益

据美国心脏协会(AHA)年会上公布的肾动脉硬化病变心血管结局(CORAL)试验结果，对动脉硬化性肾动脉狭窄合并高血压或慢性肾病的患者采用综合药物治疗联合肾动脉支架置入在预防临床事件方面并未产生明显收益。该试验结果同步在线发表于《新英格兰医学杂志》。

CORAL试验是由美国托莱多大学的Christopher J. Cooper医生及其同事进行的一项随机、对照、多中心、开标签试验，受试者为有动脉硬化性肾动脉狭窄合并慢性肾病或收缩性高血压(尽管服用了至少2种抗高血压药物)的患者，平均年龄为69岁，招募时间为2005年5月~2010年1月。研究方案规定的强制性用药(除非有禁忌)包括血管紧张素Ⅱ型-1受体阻断剂坎地沙坦联合或不联合氢氯噻嗪，及氨氯地平-阿托伐他汀配伍用药，后两种药物根据血压和血脂状况进行剂量调整。有459例患者被随机分配接受药物治疗联合肾动脉支架置入，472例患者被随机分配接受单纯药物治疗，其主要复合重点由心血管或肾脏原因引起的死亡、心肌梗死、卒中、因心力衰竭住院、进行性肾功能不全或对肾脏置换疗法的需求构成。


Christopher Cooper医生

在43个月的中位随访期中，联合治疗组与单纯药物治疗组之间在主要复合终点的发生率上没有显著差异(分别为35.1%和35.8%；支架置入的危险比，0.94)。并且，治疗组之间在复合主要终点的各项组分的发生率或全因死亡率上也无显著差异。不过，支架置入组患者的收缩压出现一致性的适度改善(与单纯药物治疗组相比，降低2.33 mmHg)。由于肾动脉狭窄在高血压患者中占1%~5%，在65岁以上人群中占7%，因此本研究的结果具有重要意义。

尽管20世纪90年代的控制不佳的研究提示，肾动脉血管成形术或支架置入使收缩压显著降低，并稳定了慢性肾病病情(这些研究结果导致1996~2000年间美国联邦医疗保险受益人的手术量增加364%)，但随后的随机试验并未显示肾动脉血管成形术对血压或肾动脉支架置入对肾功能有任何增益。

当前的研究是首个具体评价临床结局的研究之一，根据其结果判定，未联合支架置入的单纯药物治疗显然是大多数动脉硬化性肾动脉狭窄患者的首选治疗策略。在阐释本研究结果时，一个关键问题就是给予CORAL受试者的药物治疗是否能在临床实践中沿用。本研究的药物治疗包括血管紧张素受体阻断剂联用或不联用噻嗪类利尿药，配伍氨氯地平控制血压。另外，受试者还接受血小板药物治疗和阿托伐他汀控制血脂水平，并根据临床实践指南对糖尿病进行管理。采用这种方案，接受单纯药物治疗的患者获得了极好的心血管和肾脏结局，尽管其年龄偏大，高血压、糖尿病、慢性肾病及其他合并的心血管疾病的发病率高。

美国国家心肺血液研究所和美国国家卫生研究院为本试验提供了资助，另外Cordis公司(捐赠了短头Angioguard装置)和辉瑞公司也为本研究提供了支持。阿斯利康和辉瑞捐赠了药物。Cooper医生无利益冲突的报告。所有研究者的具体披露内容见nejm.org上的全文。

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By: SHARON WORCESTER, Cardiology News Digital Network

Adding renal-artery stenting to comprehensive medical therapy did not confer significant benefit with respect to the prevention of clinical events in patients with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease in the randomized controlled CORAL trial.

During a median follow-up of 43 months in the multicenter, open-label trial, the rate of a primary composite endpoint consisting of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for heart failure, progressive renal insufficiency, or the need for renal replacement therapy did not differ significantly between 459 patients randomized to receive medical therapy plus renal-artery stenting, and 472 patients randomized to receive medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94), Dr. Christopher J. Cooper reported at the American Heart Association scientific sessions.

Furthermore, no significant differences were seen between the treatment groups in the rates of the individual components of the composite primary endpoint, or in all-cause mortality. There was, however, a consistent, modest improvement in systolic blood pressure in the stent group (–2.33 mm Hg vs. the medication only group), noted Dr. Cooper of the University of Toledo (Ohio) and his coinvestigators.

The findings of the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial were published online simultaneously with the Nov. 18 presentation (N. Engl. J. Med. 2013 Nov. 18 [doi:10.1056/NE/NEJMoa1310753]).

CORAL comprised adults with a mean age of 69 years who had atherosclerotic renal-artery stenosis and either chronic kidney disease or systolic hypertension (despite taking at least two antihypertensive drugs). They were recruited during May 2005–January 2010.

Mandated medications as per the study protocol (unless contraindicated) included the angiotensin II type-1 receptor blocker candesartan with or without hydrochlorothiazide, and the combination agent amlodipine-atorvastatin dose-adjusted on the basis of blood pressure and lipid status.

The findings are important because renal artery stenosis is present in 1%-5% of people with hypertension, and in up to 7% of those over age 65 years, the investigators noted.

Although uncontrolled studies in the 1990s suggested that renal-artery angioplasty or stenting results in significant reductions in systolic blood pressure and stabilization of chronic kidney disease (findings which led to a 364% increase in the number of procedures among Medicare beneficiaries between 1996 and 2000), subsequent randomized trials failed to show a benefit of renal-artery angioplasty on blood pressure or of renal-artery stenting on kidney function, they noted.

The current study is among the first to specifically assess clinical outcomes, and based on the findings, "it is clear that medical therapy without stenting is the preferred management strategy for the majority of people with atherosclerotic renal-artery stenosis," they said.

"A key issue in the interpretation of our results is whether the medical therapy that was given to CORAL participants can be replicated in clinical practice. The medical therapy in our study included the use of an angiotensin-receptor blocker, with or without a thiazide-type diuretic, with the addition of amlodipine for blood-pressure control. In addition, participants received antiplatelet therapy and atorvastatin for management of lipid levels, and diabetes was managed according to clinical practice guidelines," they wrote, noting that with this regimen, "patients who received medical treatment alone had remarkably good cardiovascular and renal outcomes, despite their advanced age and the high rates of hypertension, diabetes, chronic kidney disease, and other coexisting cardiovascular conditions."

The National Heart, Lung, and Blood Institute and the National Institutes of Health funded the trial, with support from Cordis – which donated a short-tip Angioguard device – and Pfizer. AstraZeneca and Pfizer donated medications. Dr. Cooper reported having no conflicts of interest. Detailed disclosures for all investigators are available with the full text of the article at nejm.org.