Stenting for atherosclerotic renal artery stenosis: Another nail in the coffin

Despite a lack of strong evidence, angioplasty and stenting of atherosclerotic renal artery stenosis (RAS) became a common intervention in the last decade. It was often performed on incidental lesions discovered  during “drive-by” angiography in cardiac procedures. In the last few years, enthusiasm has cooled as two randomized trials; the ASTRAL and STAR trials have failed to show any benefit of the procedure.The ASTRAL trial received significant criticism in some corners of the medical press –as headlines like this show! 

The CORAL trial recently reported in the NEJM has added to the weight of evidence against the procedure. It included 947 patients with either systolic hypertension >155mmHg on two agents or an eGFR <60ml/min and RAS of >80% or >60% with a pressure gradient > 20mmHg. All patients received, amlodipine, atorvastatin, and candesartan +/- hydroclorothiazide.

In short there was no difference in the primary and composite endpoints of Death, MI, Stroke, heart failure, progression of CKD and need for RRT. The only exception was for that of BP in which a significant but minor (2mmHg) drop in the intervention arm.

This is another large, RCT demonstrating a lack of benefit or renal artery stenting, therefore for the vast majority of patients with RAS and either hypertension or CKD, management of RAS should be limited to medical therapy.

There remains uncertainty around patient groups in which their may still be benefit such as those with severe stenosis to a single functioning kidney, severe stenosis and AKI and patients flash pulmonary oedema. It is hard to imagine recruitment of these groups in numbers sufficient to adequately power a clinical trial.

Posted by Jonathan Dick

ASTRAL Trial

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.