Background: Atherosclerotic renal artery stenosis is a problem with no consensus on diagnosis or therapy. The consequences of renal ischemia are neuroendocrine activation, hypertension, and renal insufficiency that can potentially result in acceleration of atherosclerosis, further renal dysfunction, myocardial infarction, heart failure, stroke, and death. Whether revascularization improves clinical outcomes when compared with optimum medical therapy is unknown. Methods: CORAL is a randomized clinical trial contrasting optimum medical therapy alone to stenting with optimum medical therapy on a composite cardiovascular and renal end point: cardiovascular or renal death, myocardial infarction, hospitalization for congestive heart failure, stroke, doubling of serum creatinine, and need for renal replacement therapy. The secondary end points evaluate the effectiveness of revascularization in important subgroups of patients and with respect to all-cause mortality, kidney function, renal artery patency, microvascular renal function, and blood pressure control. We will also correlate stenosis severity with longitudinal renal function and determine the value of stenting from the perspectives of quality of life and cost-effectiveness. The primary entry criteria are (1) an atherosclerotic renal stenosis of ≥60% with a 20 mm Hg systolic pressure gradient or ≥80% with no gradient necessary and (2) systolic hypertension of ≥155 mm Hg on ≥2 antihypertensive medications. Randomization will occur in 1080 subjects. The study has 90% power to detect a 28% reduction in primary end point hazard rate. Conclusions: CORAL represents a unique opportunity to determine the incremental value of stent revascularization, in addition to optimal medical therapy, for the treatment of atherosclerotic renal artery stenosis.
Bibliographical noteFunding Information:
The primary end point is event-free survival from CV and renal adverse events, defined as a composite of CV or renal death, stroke, MI, hospitalization for CHF, progressive renal insufficiency, or need for permanent renal replacement therapy. The end point will be adjudicated by an independent Clinical Events Committee. The study is designed to detect a threshold of effect size of 25%. This threshold is a clinically reasonable goal for an expensive and invasive treatment with an expected event rate of 30% at 24 months and results in 90% power with a sample of 1080 randomized patients. The study was designed by a consortium of investigators composed of members from the interventional radiology, interventional cardiology, nephrology, and vascular medicine communities, and is funded by the National Heart Lung and Blood Institute of the National Institutes of Health (NIH). In addition, support from the industry has included provision of candesartan and candesartan-hydrochlorothiazide by AstraZeneca (Wilmington, DE), and study devices (Genesis stent and Angioguard RX XP short-tip) by Cordis Endovascular (Warren, NJ), although study governance is independent of industry support. An independent Data and Safety Monitoring Board, appointed by the NIH, will monitor safety and efficacy during the study.