Transcript Controversies in renal arterial interventions.

Controversies in renal arterial
interventions.
ACHILLES CHATZIIOANNOU, MD
Assoc. Professor of Radiology
American Board of Radiology
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60-year old
male.
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Hypertension
(180/100)
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3 anti-HTN
medications
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Cr: 2,1 mg/dl
•Normotensive with one medication.
•Cr=1.1mg/dl
Herculink 6X18-mm
Renovascular Hypertension (RVH)
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Classic studies by Goldblatt (1930): RAS is the
cause of RVH.
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RAS causing RVH: prevalence 3-5% of the
hypertensive patients.
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Atherosclerosis: 70-90% of RHV. FMD: 10-30%
of RVH.
Atherosclerotic disease
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The prevalence of RAS is increasing because
of population aging, and increased survival.
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>60% RAS in 6.8% of individuals > 65y.
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RAS in pts undergoing coronary DSA: 18%20%.
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RAS in pts undergoing peripheral DSA: 35%50%.
Fibromuscular Dysplasia (FMD)
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Young patients –more
commonly females.
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Medial fibroplasia
(80%).
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Location: distal main
renal artery, 25% into
1st order branches.
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>50% of patients have
bilateral disease.
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Commonly
asymptomatic (3%-6%
in Transplant donors).
Atherosclerotic disease
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Patient 6th decade or older.
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More often male.
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The majority of the lesions are
incidental findings.
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Ostial lesions: within 1-cm
from aorta.
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Truncal lesions (less than
10%): more than 1-cm.
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50% have bilateral disease.
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12%-20% of stenoses>75%
will progress to total occlusion
within one year (?)
Manifestations of Renovascular Disease
(Textor SC, 2004)
Renal Artery
Stenosis
Incidental
RAS
Renovascular
Hypertension
Ischemic
Nephropathy
Accelerated
CV Disease
CHF
Stroke
Endovascular treatment (PTA-stents)
is always indicated in RAS?
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7660 interventions in 1996
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18520 interventions in 2000
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2.8-fold increase by interventional
cardiologists (“drive-by”).
Medicare data
Why should we NOT treat RAS
whenever found?
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Complication rates: 13%-24%.
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Procedure-related mortality: 2%.
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Worsening of renal function (cholesterol
embo).
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Restenosis: 11%-25%.
Indications for
revascularization in RAS
When should we proceed to
revascularization if a patient has
RAS?
Treat RAS whenever found (easier when
early, avoid progression to occlusion).
1.
Progressive nature of ARVD,
progressing at the rate of 10% per
year (45%-60% progression rate in 47 year f-u)
2.
Pre-occlusive lesions (70-90%): risk
of occlusion 40%. .
JVIR 2002
Is there a role for “prophylactic”
treatment of hemodynamically
significant RAS in pts with normal
RF, normotensive, or with easily
controlled HTN?
NO
Renal artery stenting can treat patients
with RAS and hypertension
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In FMD: HTN cured in 40%; improved in
51%; cumulative benefit 87%@10 years.
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In ARVD: cure 11%; improvement 54%
[PTA meta-analysis incl 895 pts].
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Use of stents: benefit in 71% [300 pts
Lederman]; benefit in 43%-54% [163 pts
Dorros].
Ischemic nephropathy
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Kidney damage secondary to RAS.
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Not true “ischemia”, rather renal hypoperfusion
with impaired nephron function.
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RAS is present in 22% of patients >50years entering dialysis.
Ischemic nephropathy
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Progressive disease
– Lesion progression 20% per year.
– Renal atrophy 10% per year.
– Artery occlusion 5% per year.
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RAS is a marker of increased cardiovascular
mortality, predictors:
– Older age
– Impaired renal function
– Bilateral RAS
Acute renal failure in patients with RAS
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1-14 days after the initiation of treatment
with ACE inhibitors.
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After the use of diuterics or other
antihypertensive drugs.
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After major surgery.
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After the spontaneous progression of
RAS to total occlusion.
Results of revascularization for ischemic
nephropathy
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32 patients with unexplained renal
impairment and RAS were treated with
renal artery stent.
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In 70% of the patients the renal function
improved or stabilized (p<0.007).
Harden et al, Lancet
1997
Results of revascularization for ischemic
nephropathy
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33 patients with bilateral RAS or RAS in
solitary kidney.
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Follow up: 20±11 months.
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Significant improvement in 72%; mild
improvement in 28%.
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Preservation of renal size in all patients.
Watson et al. Circulation 2000
Signs that a patient with ischemic nephropathy
will benefit from revascularization
1.
Normal distal arterioles.
2.
Bilateral disease.
3.
Recent onset of renal insufficiency.
4.
Resistive Index (Doppler sonography) <80
5.
Extremely limited renal function (cr>2,5
mg/dl or 220 μmol/l)*
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*Uder M, Huke U CVIR 2005
Percutaneous revascularization
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Technical success:98-100%
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Long term patency rate 85%-98%
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Complications:
– Mortality 1-3%
– Major complications: 3-5%
– Minor complications 10-20%
An analysis of the pooled results of studies of
conventional balloon angioplasty in 1118
patients
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Hospital death 0.5%
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Nephrectomy 0.3%
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Renal surgery 2%
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Occlusion of a side branch of the renal artery
2.2%
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Cholesterol embolization 1.1%
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Injury at the site of vascular access 2.3%
The indications and results of PTA and stenting in renal artery stenosis.
SeminVasc Surg 1996;9:188-197
Evidence
3 randomized controlled trials compared medical
treatment to percutaneous renal
revascularization:
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DRASTIC: Dutch Renal Artery Stenosis
Intervention Cooperative Study Group
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EMMA: Essai Multicentrique Medicaments vs
Angioplastie Study Group
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SNRASCG: Scottish and Newcastle Renal
Artery Stenosis Collaborative Group
Systolic and Diastolic BP
•SNRASCG : no difference
•EMMA: no significant difference
•DRASTIC: no significant difference
•7%(4 patients) in the PTA group vs. none in the
medical treatment group had cure of their HTN
•In the patients that underwent PTA from medical
treatment group due to refractory HTN or
progressive renal dysfunction: there was a
significant decrease in BP (P<0.001)
•Nordman.
Cochrane Library of Systematic Reviews. 2004:;vol 2
Number of Antihypertensive Agents
•SNRASCG : no difference
•EMMA: significant decrease in the defined
daily dose of antihypertensive agents
•DRASTIC: significant decrease in the number
and defined daily dose of antihypertensive
agents at 3 months. This difference was no
longer significant at 12 months after cross over
of medically treated patients to PTA
•Nordman.
Cochrane Library of Systematic Reviews. 2004:;vol 2
Meta-analysis PTRA vs Medical treatment
Ives et al. Nephrol Dial Transplant 2003
Nordmann et al. Am J Med 2003
Change in blood pressure
Renal function
No significant difference in serum
creatinine or creatinine clearance
between the two groups in any of the
trials.
•Nordman.
Cochrane Library of Systematic Reviews. 2004:;vol 2
Meta-analysis PTRA vs Medicatie
Ives et al. Nephrol Dial Transplant 2003
Nordmann et al. Am J Med 2003
Change in renal function
Cardiovascular and
Renovascular Complications
In all studies, the risk of cardiovascular and
renovascular complications were lower in the
PTA vs. Medical treatment group (9.6%
vs24.5%)
•Cardiovascular complications (myocardial infarction, angina, heart failure, stroke,
non-procedure-related symptomatic hypotension, or cardiovascular death)
•Renovascular complications (defined as an increase of serum creatinine of more than
50 per cent, cholesterol embolisation, development of renal failure, total occlusion
of the stenotic artery, dissection of the renal artery, major complication during
balloon angioplasty other than Haematoma at the puncture site, or need for
dialysis)
Conclusions
1.
In patients whose blood pressure could be
controlled with medical therapy alone, no trial was
able to demonstrate a statistically significant
difference in blood pressure between balloon
angioplasty and medical therapy.
2.
In patients with refractory hypertension to
medical therapy, the results of the DRASTIC trial
demonstrated that balloon angioplasty was better
than medical therapy in respect of more efficient
blood pressure control.
PTA vs Stent
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85 patients with ostial RAS.
Intention-to-treat analysis.
Inclusion:
– RAS>50%
– HTN
– Positive captopril renography OR increase Cr after
ACE-I
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Exclusion:
– Renal size < 8cm
– <25% renal function by renography
van de Ven et al. Lancet 1999
PTRA versus Stent
van de Ven et al. Lancet 1999
Cumulative primary patency (%)
Cumulative primary patency
100
Stent
80
60
p < 0.001
40
20
Angioplasty
0
0
1
2
3
4
5
6
Time after procedure (months)
Stent
42
37
37
36
36
35
35
30
PTRA
42
24
23
21
21
21
21
12
PTRA versus Stent
van de Ven et al. Lancet 1999
Blood pressure
Renal function
100%
80%
77%
80%
57%
60%
49%
PTRA
Stent
40%
20%
0%
Cure / improved
Improved / stable
“The majority of patients with significant
RAS and hypertension or renal function
loss can be treated medically without the
risk of mortality or progression to endstage disease”.
Exceptions: Bilateral RAS; RAS in solitary
kidney.
2X mortality risk; 1.5X risk of renal failure.
Care if renal mass loss OR loss of renal function
when ACE inhibitor is used!
Angioplasty and Stent for
Renal Arterial Lesions
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Multicenter Randomized clinical trial.
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Approx 1000 pts will be randomized to
optimal medical therapy or to stenting
with optimal medical therapy
Revascularization versus Medical Therapy for Renal-Artery
Stenosis
The ASTRAL Investigators
Background Percutaneous revascularization of the renal arteries improves patency in
atherosclerotic renovascular disease, yet evidence of a clinical benefit is limited.
Methods In a randomized, unblinded trial, we assigned 806 patients with atherosclerotic
renovascular disease either to undergo revascularization in addition to receiving medical
therapy or to receive medical therapy alone. The primary outcome was renal function, as
measured by the reciprocal of the serum creatinine level (a measure that has a linear
relationship with creatinine clearance). Secondary outcomes were blood pressure, the time to
renal and major cardiovascular events, and mortality. The median follow-up was 34 months.
Results During a 5-year period, the rate of progression of renal impairment (as shown by the
slope of the reciprocal of the serum creatinine level) was –0.07x10–3 liters per micromole per
year in the revascularization group, as compared with –0.13x10–3 liters per micromole per year
in the medical-therapy group, a difference favoring revascularization of 0.06x10–3 liters per
micromole per year (95% confidence interval [CI], –0.002 to 0.13; P=0.06). Over the same
time, the mean serum creatinine level was 1.6 µmol per liter (95% CI, –8.4 to 5.2 [0.02 mg per
deciliter; 95% CI, –0.10 to 0.06]) lower in the revascularization group than in the medicaltherapy group. There was no significant between-group difference in systolic blood pressure;
the decrease in diastolic blood pressure was smaller in the revascularization group than in the
medical-therapy group. The two study groups had similar rates of renal events (hazard ratio in
the revascularization group, 0.97; 95% CI, 0.67 to 1.40; P=0.88), major cardiovascular events
(hazard ratio, 0.94; 95% CI, 0.75 to 1.19; P=0.61), and death (hazard ratio, 0.90; 95% CI, 0.69
to 1.18; P=0.46). Serious complications associated with revascularization occurred in 23
patients, including 2 deaths and 3 amputations of toes or limbs.
Conclusions We found substantial risks but no evidence of a worthwhile clinical benefit from
revascularization in patients with atherosclerotic renovascular disease.
Volume 361:1953-1962 November 2009
Renal Function in Patients with Renal-Artery Stenosis Treated with Revascularization or Medical
Therapy Alone
The ASTRAL Investigators. N Engl J Med 2009;361:1953-1962
Kaplan-Meier Curves for the Time to the First Renal and Cardiovascular Events
The ASTRAL Investigators. N Engl J Med 2009;361:1953-1962
Kaplan-Meier Curves for Overall Survival
The ASTRAL Investigators. N Engl J Med 2009;361:1953-1962
Systolic and Diastolic Blood Pressure
The ASTRAL Investigators. N Engl J Med 2009;361:1953-1962
Last question: why does renal function
may deteriorate after revascularization?
1.
Contrast nephropathy.
2.
Cholesterol embolization.
3.
Exposure of diseased glomeruli to high
blood pressure.
Is there any role for distal
protection?
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65 hypertensive patients with
significant RAS were stented with
distal protection.
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2 protection devices were used:
– Guardwire: 2 sizes [2.5-5mm and 3-6 mm]
– Filterwire: 3.5-5.5 mm]
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Henry et al. Cath and cardio interv 2003
Results
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ASA and plavix for 4 weeks.
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Follow up: average 22 months; DSA if
restenosis suspected by US.
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Cr improved or stabilized in ALL patients.
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The patients with moderate to severe
renal impairment benefited the most.
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Blood pressure control in all.
Distal protection devices
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Visible debris in filter
in all cases.
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Atheromatous
plaques, necrotic
cores, thrombi,
macrophages.
Indications for revascularization of RAS
1.
Hypertensive control.
1. Reasonable likelihood of cure.
1.
2.
3.
Onset before age 30.
Recent onset after age 60.
FMD.
2. Hypertension is “refractory” to medical treatment
with at least 3 different class drugs including 1
diuretic.
3. “Accelerated” hypertension.
4. “Malignant” hypertension [end-organ damage: LV
hypertrophy, CHF, visual or neurological
disturbance, grade III-IV retinopathy].
5. Non compliant patient.
Indications
2.
Renal salvage
1. Unexplained worsening of renal function.
2. Loss of renal mass during anti-hypertensive
therapy.
3. Impairment of renal function secondary to
hypertensive treatment particularly to ACE inhibitor.
4. Progression of RAS under surveillance.
3.
Cardiac Disturbance syndrome
1. Flash pulmonary edema.
2. Unstable angina.
3. Worsening of CHF.
Case #1
S/p EVAR new onset of HTN
Case # 2
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50-year-old male with solitary kidney.
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Smoker.
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Refractory HTN.
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Cr: 3.8 mg/dl
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B/P: 160/80
mmHg
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Cr: 1.8 mg/dl
The patient was re-admitted 18 months
later with Cr: 2.8 mg/dl, and BP:
180/90 mmHg.
Conclusions
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Incidental RAS is not an indication for
revascularization.
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Hypertensive patients with RAS may
benefit from revascularization if HTN is
“refractory” to medical treatment.
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Revascularization is indicated in
hypertensive patients with RAS if renal
mass loss or renal function decline is
observed during hypertensive treatment.