Another day, another negative study… this is getting painful! The large, randomized ASTRAL trial comparing renal revascularization to medical therapy found no benefit, and substantial increased risk, in the interventional arm.
806 patients with atherosclerotic reno-vascular disease were randomized to undergo revascularization in addition to receiving medical therapy or to receive medical therapy alone. After 34 months of follow-up, there were no significant differences between the two groups in the rates of renal events, major cardiovascular events, or death. There were some marginal positive outcomes in the intervention group, including better renal function (p = 0.06) and statistically significant reduction in blood pressure medications. However, 23 patients in the revascularization arm experienced serious complications, including 2 deaths and 3 amputations.
ASTRAL has been criticized on a few fronts. First, the trial design is based on the “principle of equipoise”. Essentially, the investigators only enrolled patients in whom they were uncertain as to whether they would derive clinical benefit from revascularization. As such, many patients enrolled in the trial had lesions of dubious clinical significance, as more high-risk patients would not have been randomized. As an example, 40% of those enrolled had less than 70% stenosis, and some patients with stenoses as low as 60% were included.
Personally, I feel a bit sorry for the authors here. They set out to answer the specific question of what to do with the incidentally discovered, moderate-grade renal artery lesion in a CKD patient, and are then criticized for designing a trial that excludes patients in whom intervention is very likely to benefit. Critics of the trial claim that many of the lesions chosen for intervention were of unclear clinical significance, but I believe that was exactly the point. It’s not as if the management approach to such lesions has been firmly established. The bottom line with intervention in renal arterial disease is that we are doing a poor job in identifying the right kidney in the right patient, and there is a lot more work to do. ASTRAL is step in the right direction.
6 comments:
(The paragraphs below are what I wrote as a comment on jwatch.org. The real fault appears to be with the editors who chose an article title which is hardly supported by the data. Here, the bottom line is that when the clinician is unsure, there is no evident benefit to 'doing something' or at least no loss from treating medically, and, as you point out, this really is a very valuable insight. The diligent authors are not well served by the title.)
The real conclusion seems to be that renal revascularization doesn't help in those cases where the treating physician is 'uncertain' it would help. Unfortunately, the authors did not include the data from patients who were thought to 'require' revascularization. So, it seems that the study design limited the possible conclusions, and the authors rightly acknowledge this. Thus, the title 'Revascularization Is Ineffective for Atherosclerotic Renal Artery Stenosis' is not actually supported by the evidence presented. It'll take a clever editor to create an accurate title for this paper.
Since some 25% of persons in the US over age 65 have some detectable renal artery stenosis, it's obvious that most don't require revascularization. However, if they do have 'renovascular hypertension' (RVH, by the way, is defined as a retrospective diagnosis) or, perhaps more accurately, 'renoprival disease', they may benefit from renal revascularization. Unfortunately, the 'sound bite' view of this article, even the title, may be improperly used by insurers to deny coverage for even those carefully selected patients who may actually benefit from revascularization.
I agree completely. So much of Nephrology rests upon complex clinical judgement, something that has been quite difficult to capture in the design of trials e.g. timing of dialysis, CVVH vs IHD etc...
It's disappointing when a thoughtfully designed trial like ASTRAL comes to grief for the want of a neat soundbite...
I took the Nephrology Boards yesterday....relevant to this post, there were a few questions about management of renal artery stenosis in which one had to choose between medical management versus endovascular revascularization....I personally find it somewhat comical that these questions made it onto the exam, as I don't think anybody has any real conclusive evidence as to what the right answer should be!
I completely agree with your comments Nathan. Notice not a single question about anemia treatment except to recognize chronic inflammation as a cause for epo resistance, but several questions relating to renal artery stenosis Rx.
ASTRAL's investigators designed their trial in a very unuseful way to draw firm conclusions.
Pts enrolled in the revascularization group recieved a better pharmacologic therapy than pts in the medical therapy group. This difference was statistically significant from the beginning and was maintained throughout the study period...
I think you all have a valid point on what you are saying, it a topic of much interest for me, and I enjoyed reading your comments.
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