“Re: Renal Artery Stenting is no Longer Indicated After ASTRAL: Pros and Cons”

Abstract

The authors of the ASTRAL trial [1] were interested to read the debate about the trial in CVIR [2]. They have listened with some bemusement to the criticisms that have been levelled at the study in this debate and other publications [3]. Although constructive criticism and intelligent debate is healthy, it appears that many are confused about the methodology and results of the ASTRAL Trial. It is important to be clear that after years of small case series, cohorts, and randomized, controlled trials, ASTRAL succeeded in randomizing a significant number of patients with chronic renal impairment to renal stenting and best medical therapy against best medical therapy alone. It is more than 7.5-times larger than the previous largest reported study [4]. This was quite an achievement. Some critics of ASTRAL did not enter any patients into the trial, either because they were never ‘‘uncertain’’ how to treat their patients (lucky them) or they misunderstood the ‘‘uncertainty principle.’’ Patient eligibility based on the ‘‘uncertainty principle’’ has been widely used in a number of trials [5] and is scientifically and ethically acceptable in those situations where a clinician is uncertain how to treat a patient. This principle resulted in a heterogeneous patient population being entered into the trial, as different clinicians had different areas of uncertainty regarding the use of renal stenting. One of the criticisms levelled at ASTRAL is that many patients (and especially patients considered likely to benefit from renal stenting) were not entered into the trial. However, randomization is only ethically justified if one is unsure of the benefits of intervention to the individual patient. In the event, the patients recruited to ASTRAL did not have trivial disease. The majority had severe renal artery stenosis and/or impaired renal function. Randomization was stratified according to disease severity and the number in each prespecified subgroup was substantial (often larger in patient numbers than the previous trials). We found no evidence of benefit for renal stenting in any of the subgroup analyses or in the post-hoc analysis of the most severe patients. Those who criticize the ASTRAL trial on the basis that it excluded those patients who were likely to benefit from intervention have misunderstood the uncertainty principle. It is impossible to know why individual patients were excluded, but it is likely that many patients with accepted indications for intervention, such as acute anuric renal failure, very rapid decline in renal function, malignant hypertension, and flash pulmonary edema, were not randomized. Fibromuscular disease was a specific exclusion criterion. Critics should recognize that ASTRAL is not at a variance with all the previous small studies mentioned above. In fact many of these results are supported by the ASTRAL analyses. The difference between ASTRAL and these other studies is that nearly all of the patients in ASTRAL were taking best medical therapy. Quite simply, the benefits attributed to angioplasty or stenting in previous studies could be achieved by best medical therapy alone. It is important to recognize that no other study on renal artery N. Chalmers (&) Department of Radiology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK e-mail: Nicholas.chalmers@cmft.nhs.uk