Misleading Results of Randomized Trials: The Example of Renal Artery Stenting

Randomized controlled trials are considered the most reliable form of evidence. However, when their results disagree with clinical experience, the validity of their findings merits critical examination. In the recent randomized multicenter Stenting in Renal Dysfunction Caused by Atherosclerotic Renal Artery Stenosis (STAR) trial that assessed the efficacy of renal artery stenting, Bax and colleagues reported little or no benefit compared with medical treatment. The authors therefore recommended, particularly in view of the risks of the procedure, that stenting be avoided in treating patients with renal artery stenosis. This conclusion, along with the previously reported results of the Dutch Renal Artery Stenosis Intervention (DRASTIC) trial, will likely reduce the use of renal artery stenting and might also affect insurer authorization for such procedures. The purpose of this editorial is to: (1) challenge the conclusion of the STAR trial, and (2) more broadly raise concern about uncritical acceptance of misleading conclusions from randomized trials, particularly when they disagree with clinical experience. Having personally observed many patients who, following renal artery angioplasty with or without stenting, experienced dramatic and nearly immediate amelioration of problems such as refractory hypertension, congestive heart failure, and renal insufficiency, it is inconceivable to us, and to many others, that these procedures are of no benefit. When a renal artery procedure is followed by diuresis of 6 L within 24 hours and a dramatic amelioration of heart failure, or by a rapid and sustained fall in blood pressure and ⁄or serum creatinine level, the benefit of the procedure is indisputable, at least in some patients. This clinical experience is supported by many uncontrolled case series that have documented benefit. Unfortunately, there is also no doubt that renal artery stenting is overused and employed in cases where there is little or no expectation of benefit, while exposing patients to harm. The question that needs to be asked is not whether the procedure can help patients, but how to select patients most likely to benefit from stenting while avoiding the procedure and its associated risks in those least likely to benefit. This trial did not address that important question. An obvious question is: if renal artery stenting does benefit patients, why did this randomized controlled trial not show it? In this case, several factors can explain the misleading negative result. In this and other studies, a crucial issue is the criteria used for selection of patients. In the STAR trial, 62.5% (40 of 64) of the patients randomized to the stenting group and included in the intentionto-treat analysis were predictably unlikely to benefit for the following reasons: (1) 12 patients who met entry criteria of >50% renal artery stenosis, determined largely by noninvasive imaging, turned out to have stenoses of <50% and were not even stented; (2) an additional 22 patients had 50% to 70% stenosis, which usually is not hemodynamically significant; and (3) in 6 other patients, stenting was From the New York Presbyterian Hospital, Weill ⁄ Cornell Medical Center, New York, NY Address for correspondence: Samual J. Mann, MD, New York Presbyterian Hospital, Weill ⁄ Cornell Medical Center, 525 East 68th Street, L-1, New York, NY 10021 E-mail: sjmann@med.cornell. edu