On the final day of CX32, there was excitement and discussion at the Renal Session. The recent randomised trials which found that renal artery stenting showed no benefits over medical therapy, STAR and ASTRAL, came in for considerable criticism from some speakers. The session was chaired by Jon Moss, principal investigator of ASTRAL. Delegates were told that unless the CORAL trial, the results of which are awaited in early 2011, unveils data clearly showing the benefit of intervention, the future of renal artery stenting is very much in doubt, even though most clinicians believe a subgroup of patients do benefit from revascularisation.
Thomas Zeller, Heart-Center, Bad Krozingen, Germany, presented on the topic: “Critical review of indications for renal artery stenting: Do randomised data give the answer?”
He told delegates,“Do not base your decisions entirely on randomised controlled trials alone because real world registries are more likely to reflect reality.”
Zeller said the randomised controlled trials prior to ASTRAL (Angioplasty and stent for renal artery lesions), which is the largest renal revascularisation trial to date, included 1) Randomised comparison of percutaneous angioplasty vs. continued medical therapy for hypertensive patients with atheromatous renal artery stenosis (n=55) ( Webster et al.: J Hum Hypertens 1998), 2) Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis (EMMA; n=48) ( Plouin et al.: Hypertension 1998 ) and 3) The effect of balloon angioplasty on hypertension in atherosclerotic renal artery stenosis (DRASTIC; n=106). (Van Jaarsveld et al.: NEJM 2000).
Zeller said that the results of these were limited by the fact that in about 50% of lesions, stenosis was less than 70%. “Also, in the DRASTIC trial, 15% of lesions showed less than 50% stenosis. Other limitations included small numbers,“ he said.
Zeller told delegates that STAR and ASTRAL were limited by patient selection bias and poor study design.
Zeller said, “The lesson learned from ASTRAL is that patients with atherosclerotic renal artery stenosis in whom the need for revascularisation is uncertain do not get better with revascularisation, as with optimised drug therapy.”
Also, said Zeller, patients with the highest probability of treatment effect are frequently excluded from randomised trials. To overcome the selection bias of a randomised trial comparing revascularisation with conservative therapy, upcoming studies should include a registry arm enrolling all eligible patients who refused randomisation. The registry arm with the same restrictions in enrollment criteria as the randomised study arm might be more representative for a real world scenario because even the most severe lesions including bilateral stenoses and stenoses of single kidney providing renal arteries will be enrolled in such a registry arm, he said.
Michael R Jaff, Harvard Medical School, Boston, USA, spoke on the patient selection in these trials and said, “We are missing a window of opportunity, at least in the United States, and it is closing really fast. Unfortunately, I am worried that CORAL is not going to solve this problem, because not every patient with RAS was enrolled in CORAL. In clinical trials, We have not selected the right patients properly. We have missed an opportunity, we have not studied renal artery intervention necessarily in the right patient population. Depending on the results of CORAL, the Federal Government will tell us what to do, because we were not able to provide them definitive data.”
Jim Reekers, University of Amsterdam, The Netherlands, presented on “Primary stent placement for renal artery stenosis and renal functional impairment: Outcome of the randomised trials”. He drew attention to the fact that he was speaking on the newer randomised trials – the STAR study, ASTRAL and “NIDER” which is an Italian study.
Reekers identified some of the issues with the STAR study. “There was a very small number in each group, a short follow-up, and no corelab for Quantitative Vessel analysis (QVA). Additionally, 28% randomised to stent, did not receive a stent and medical therapy was poorly defined,” he said.
ASTRAL too came in for some stick. “This trial was underpowered with a short follow-up. Of 403 patients assigned to stent, 23.6% did not receive a stent. Seven percent of patients who were randomised to receive a stent, only had percutaneous transluminal renal angioplasty. Twelve per cent who had a stent had a residual stenosis >50%, there was a high complication rate, medical therapy was poorly defined, there was no corelab adjudication and there was a selection bias toward enrolling asymptomatic or minimally symptomatic patients with non-obstructive renal artery lesions, i.e. patients unlikely to benefit from revascularisation,” he said.
In summary, said Reekers, “Results from the recent randomised controlled trials are inconclusive due to inadequately powered, poorly defined medical treatment, crossovers, short follow-up, inconsistent use of stents, enrollment of patients with < 50% stenosis, use of surrogate endpoints and lack of angiographic corelab adjudication.”
He told CX32 delegates that the questions that still remain are: Does renal stenting improve survival? Does stenting improve the quality of life? Is renal stenting cost-effective? Is there a test that will accurately predict the clinical effects of a renal artery stenosis?
Roger Greenhalgh, chairman of CX32, highlighted he sympathised with the investigators of ASTRAL because the findings are counter-intuitive, just as some other trials had turned out. “EVAR 2 was one such trial,” he said. “There may be a subgroup, as Jon Moss implies, but overall the intervention has not produced the expected result,” he noted.
NOTE: The next issues of both Vascular News and Interventional News will carry an exclusive story on a round-table discussion between Jon Moss, Jim Reekers and Thomas Zeller at CX32.The discussion threw light on the issues raised by the evidence from randomised controlled trials on renal artery stenting and the future of revascularisation. Sign up to receive your free copies, here.