Download Stenting and Medical Therapy for Atherosclerotic Renal

Stenting and Medical Therapy
for Atherosclerotic Renal-Artery
Stenosis
NEJM, Jan 2014,
M Graham-Brown
28/05/14
Background
• RAS – present in 1-5% patients with HTN
• Can also lead to ischaemic nephropathy and
‘flash pulmonary oedema’
• 3 RCT’s show no effect to stenting on BP:
–
–
–
van Jaarsveld BC, Krijnen P, Pieterman H, et al. The effect of balloon angioplasty on hypertension in atherosclerotic renal- artery
stenosis. N Engl J Med 2000;342: 1007-14.
Plouin PF, Chatellier G, Darné B, Raynaud A. Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a
randomized trial. Hyperten- sion 1998;31:823-9.
Webster J, Marshall F, Abdalla M, et al. Randomised comparison of percuta- neous angioplasty vs continued medical therapy for
hypertensive patients with atheromatous renal artery stenosis. J Hum Hypertens 1998;12:329-35.
• 2 RCT’s show no benefit on progression of CKD:
–
–
15. The ASTRAL Investigators. Revascu- larization versus medical therapy for re- nal-artery stenosis. N Engl J Med 2009;
361:1953-62.
16. Bax L, Woittiez AJ, Kouwenberg HJ, et al. Stent placement in patients with atherosclerotic renal artery stenosis and impaired renal function: a randomized trial. Ann Intern Med 2009;150:840-8.
Background
• “No studies designed to assess clinical
outcomes”
• SO… “we performed a randomized clinical trial
to determine the effects of renal-artery
stenting on the incidence of important
cardiovascular and renal adverse events.”
Study oversight
• “The Cardiovascular Outcomes in Renal
Athero- sclerotic Lesions (CORAL) study was a
multi- center, open-label, randomized,
controlled trial that compared medical
therapy alone with medical therapy plus renalartery stenting in patients with atherosclerotic
renal-artery stenosis and elevated blood
pressure, chronic kidney disease, or both.”
Design and population
• Multi-centre
• Lead-in period – to ensure the expertise of the
lead for IR at each centre
• Initially patients with severe RAS were eligible
if they had HTN with systolic BP>155mm/Hg
on +2 anti-hypertensives
• Severe RAS defined as >80%, but <100% OR
60-80% stenosis with a 20mm/Hg systolic
pressure gradient
(Re-)design and population
• The threshold of 155mm/Hg was no longer
specified
• Patients who did not have systolic
hypertension but who had renal-artery
stenosis could be enrolled if they had CKD
(eGFR<60)
• Severe RAS could be identified using duplex
ultrasonography, MRA, or CTA
• All changes were made before the trial
concluded and/or the results were unblinded
Exclusion criteria
• RAS due to fibromuscular dysplasia
• CKD from a cause other than ischemic nephropathy or associated with a serum
creatinine level higher than 4.0 mg per
deciliter (354 μmol/liter)
• Kidney length of less than 7 cm
• A lesion that could not be treated with the use
of a single stent.
Randomised 1:1
• Medical therapy alone
– Anti-platelet, lipid lowering agent, BP medications,
glucose (all protocol driven)
• Medical therapy + stenting
• “Unless otherwise contraindicated, the following
medications were mandated by the protocol: the
angiotensin II type-1 receptor blocker candesartan, with or without hydrochlorothiazide, and
the combination agent amlodipine–atorvastatin,
with the dose adjusted on the basis of blood
pressure and lipid status”
End points
• The primary end point was the occurrence of
a major cardiovascular or renal event:
– Stroke
– MI
– Hospitalization for congestive heart failure
– Progressive renal insufficiency (reduction of 30%
from baseline eGFR, sustained for 60 days or
more)
– The need for permanent RRT
End points
• Secondary end-points were death from
cardiovascular/renal disease and all cause
mortality
Power Calculation
• Calculated that 1080 participants would need
to be enrolled for the study to have 90%
power to test the hypothesis that stenting
would reduce the incidence of the primary
end point by 25% (hazard ratio, 0.75) at 2
years, at a two-sided type I error rate of 0.05.
• Recruitment was slower than anticipated, and
terminated after 947 participants had
undergone randomization
Results – all analyzed on ITT
Event Free survival
Stenting and peri-procedural events
• The most common angiographic complication
was arterial dissec- tion, which occurred in 11
patients
• No one in the stent group (or in the medical
therapy–only group) required dialysis within 30
days after randomization
• One patient (0.2%) in the stent group initiated
dialysis between 30 and 90 days after
randomization
• A patient randomly assigned to medical therapy
alone had a fatal stroke on the day of
randomization
Blood Pressure
• No differences between the groups at end of
study
• BP declined throughout study period in both
groups
• No difference in the number of medications
they were taking
Conclusions
• “The CORAL trial was designed to test whether
renal-artery stenting, when added to protocoldriven contemporary medical therapy, improves
clinical outcomes in persons with atherosclerotic
renal-artery stenosis”
• “We found no benefit of stenting with respect to
the rate of the composite primary end point or
any of its individual components, including death
from cardiovascular or renal causes, stroke,
myocardial infarction, congestive heart failure,
progressive renal insufficiency, and the need for
renal-replacement therapy”
Conclusions
• “From this result, it is clear that medical
therapy without stenting is the preferred management strategy for the majority of people
with atherosclerotic renal-artery stenosis”
SO..
• We just have to get the patients to take their
medications
• #concordance