Controversies in renal arterial interventions. ACHILLES CHATZIIOANNOU, MD Assoc. Professor of...

Controversies in renal Controversies in renal

arterial interventions.arterial interventions.Controversies in renal Controversies in renal

arterial interventions.arterial interventions.

ACHILLES CHATZIIOANNOU, MDACHILLES CHATZIIOANNOU, MDAssoc. Professor of RadiologyAssoc. Professor of RadiologyAmerican Board of RadiologyAmerican Board of Radiology

• 60-year old male.

• Hypertension (180/100)

• 3 anti-HTN medications

• Cr: 2,1 mg/dl

• 60-year old male.

• Hypertension (180/100)

• 3 anti-HTN medications

• Cr: 2,1 mg/dl

Herculink 6X18-mmHerculink 6X18-mm

•Normotensive with one medicationNormotensive with one medication..•Cr=1.1mg/dlCr=1.1mg/dl

Renovascular Renovascular

Hypertension (RVH)Hypertension (RVH)

Renovascular Renovascular

Hypertension (RVH)Hypertension (RVH)• Classic studies by Goldblatt (1930): RAS is the Classic studies by Goldblatt (1930): RAS is the

cause of RVH.cause of RVH.

• RAS causing RVH: prevalence 3-5% of the RAS causing RVH: prevalence 3-5% of the hypertensive patients.hypertensive patients.

• Atherosclerosis: 70-90% of RHV. FMD: 10-30% Atherosclerosis: 70-90% of RHV. FMD: 10-30% of RVH.of RVH.

• Classic studies by Goldblatt (1930): RAS is the Classic studies by Goldblatt (1930): RAS is the cause of RVH.cause of RVH.

• RAS causing RVH: prevalence 3-5% of the RAS causing RVH: prevalence 3-5% of the hypertensive patients.hypertensive patients.

• Atherosclerosis: 70-90% of RHV. FMD: 10-30% Atherosclerosis: 70-90% of RHV. FMD: 10-30% of RVH.of RVH.

Atherosclerotic diseaseAtherosclerotic diseaseAtherosclerotic diseaseAtherosclerotic disease

• The prevalence of RAS is increasing The prevalence of RAS is increasing because of population aging, and because of population aging, and increased survival.increased survival.

• >60% RAS in 6.8% of individuals > 65y.>60% RAS in 6.8% of individuals > 65y.

• RAS in pts undergoing coronary DSA: RAS in pts undergoing coronary DSA: 18%-20%.18%-20%.

• RAS in pts undergoing peripheral DSA: RAS in pts undergoing peripheral DSA: 35%-50%.35%-50%.

• The prevalence of RAS is increasing The prevalence of RAS is increasing because of population aging, and because of population aging, and increased survival.increased survival.

• >60% RAS in 6.8% of individuals > 65y.>60% RAS in 6.8% of individuals > 65y.

• RAS in pts undergoing coronary DSA: RAS in pts undergoing coronary DSA: 18%-20%.18%-20%.

• RAS in pts undergoing peripheral DSA: RAS in pts undergoing peripheral DSA: 35%-50%.35%-50%.

Fibromuscular Dysplasia

(FMD)

Fibromuscular Dysplasia

(FMD)• Young patients –more commonly females.

• Medial fibroplasia (80%).

• Location: distal main renal artery, 25% into 1st order branches.

• >50% of patients have bilateral disease.

• Commonly asymptomatic (3%-6% in Transplant donors).

• Young patients –more commonly females.

• Medial fibroplasia (80%).

• Location: distal main renal artery, 25% into 1st order branches.

• >50% of patients have bilateral disease.

• Commonly asymptomatic (3%-6% in Transplant donors).

Atherosclerotic diseaseAtherosclerotic disease

• Patient 6th decade or older.

• More often male.

• The majority of the lesions are incidental findings.

• Ostial lesions: within 1-cm from aorta.

• Truncal lesions (less than 10%): more than 1-cm.

• 50% have bilateral disease.

• 12%-20% of stenoses>75% will progress to total occlusion within one year (?)

• Patient 6th decade or older.

• More often male.

• The majority of the lesions are incidental findings.

• Ostial lesions: within 1-cm from aorta.

• Truncal lesions (less than 10%): more than 1-cm.

• 50% have bilateral disease.

• 12%-20% of stenoses>75% will progress to total occlusion within one year (?)

Manifestations of Renovascular

Disease (Textor SC, 2004)

Manifestations of Renovascular

Disease (Textor SC, 2004)

Renal Artery Stenosis

Incidental RAS

Renovascular Hypertension

Ischemic Nephropathy

AcceleratedCV Disease

CHFStroke

Endovascular treatment (PTA-Endovascular treatment (PTA-

stents) is always indicated in stents) is always indicated in

RAS? RAS?

Endovascular treatment (PTA-Endovascular treatment (PTA-

stents) is always indicated in stents) is always indicated in

RAS? RAS? • 7660 interventions in 19967660 interventions in 1996• 18520 interventions in 200018520 interventions in 2000• 2.8-fold increase by 2.8-fold increase by

interventional cardiologists interventional cardiologists (“drive-by”).(“drive-by”).

• 7660 interventions in 19967660 interventions in 1996• 18520 interventions in 200018520 interventions in 2000• 2.8-fold increase by 2.8-fold increase by

interventional cardiologists interventional cardiologists (“drive-by”).(“drive-by”).

Medicare data

Why should we NOT treat RAS Why should we NOT treat RAS

whenever found?whenever found?

Why should we NOT treat RAS Why should we NOT treat RAS

whenever found?whenever found?

• Complication rates: 13%-24%.Complication rates: 13%-24%.

• Procedure-related mortality: 2%.Procedure-related mortality: 2%.

• Worsening of renal function Worsening of renal function (cholesterol embo).(cholesterol embo).

• Restenosis: 11%-25%.Restenosis: 11%-25%.

• Complication rates: 13%-24%.Complication rates: 13%-24%.

• Procedure-related mortality: 2%.Procedure-related mortality: 2%.

• Worsening of renal function Worsening of renal function (cholesterol embo).(cholesterol embo).

• Restenosis: 11%-25%.Restenosis: 11%-25%.

Indications for Indications for

revascularizationrevascularization in RAS in RAS

Indications for Indications for

revascularizationrevascularization in RAS in RAS

When should we proceed to revascularization if a patient

has RAS?

When should we proceed to revascularization if a patient

has RAS?

Treat RAS whenever found (easier Treat RAS whenever found (easier when early, avoid progression to when early, avoid progression to

occlusion). occlusion).

Treat RAS whenever found (easier Treat RAS whenever found (easier when early, avoid progression to when early, avoid progression to

occlusion). occlusion).

1.1. Progressive nature of ARVD, Progressive nature of ARVD, progressing at the rate of 10% progressing at the rate of 10% per year (45%-60% progression per year (45%-60% progression rate in 4-7 year f-u)rate in 4-7 year f-u)

2.2. Pre-occlusive lesions (70-90%): Pre-occlusive lesions (70-90%): risk of occlusion 40%. .risk of occlusion 40%. .

1.1. Progressive nature of ARVD, Progressive nature of ARVD, progressing at the rate of 10% progressing at the rate of 10% per year (45%-60% progression per year (45%-60% progression rate in 4-7 year f-u)rate in 4-7 year f-u)

2.2. Pre-occlusive lesions (70-90%): Pre-occlusive lesions (70-90%): risk of occlusion 40%. .risk of occlusion 40%. .

JVIR 2002

Is there a role for “prophylactic” Is there a role for “prophylactic”

treatment of hemodynamically treatment of hemodynamically

significant RAS in pts with normal significant RAS in pts with normal

RF, normotensive, or with easily RF, normotensive, or with easily

controlled HTN? controlled HTN?

Is there a role for “prophylactic” Is there a role for “prophylactic”

treatment of hemodynamically treatment of hemodynamically

significant RAS in pts with normal significant RAS in pts with normal

RF, normotensive, or with easily RF, normotensive, or with easily

controlled HTN? controlled HTN?

NONO

Renal artery stenting can treat patients Renal artery stenting can treat patients

with RAS and hypertensionwith RAS and hypertension

Renal artery stenting can treat patients Renal artery stenting can treat patients

with RAS and hypertensionwith RAS and hypertension

• In FMD: HTN cured in 40%; improved in 51%; cumulative benefit 87%@10 years.

• In ARVD: cure 11%; improvement 54% [PTA meta-analysis incl 895 pts].

• Use of stents: benefit in 71% [300 pts Lederman]; benefit in 43%-54% [163 pts Dorros].

• In FMD: HTN cured in 40%; improved in 51%; cumulative benefit 87%@10 years.

• In ARVD: cure 11%; improvement 54% [PTA meta-analysis incl 895 pts].

• Use of stents: benefit in 71% [300 pts Lederman]; benefit in 43%-54% [163 pts Dorros].

Ischemic nephropathyIschemic nephropathyIschemic nephropathyIschemic nephropathy

• Kidney damage secondary to RAS.

• Not true “ischemia”, rather renal hypoperfusion with impaired nephron function.

• RAS is present in 22% of patients >50-years entering dialysis.

• Kidney damage secondary to RAS.

• Not true “ischemia”, rather renal hypoperfusion with impaired nephron function.

• RAS is present in 22% of patients >50-years entering dialysis.

Ischemic nephropathyIschemic nephropathyIschemic nephropathyIschemic nephropathy• Progressive disease

– Lesion progression 20% per year.– Renal atrophy 10% per year.– Artery occlusion 5% per year.

• RAS is a marker of increased cardiovascular mortality, predictors:– Older age– Impaired renal function– Bilateral RAS

• Progressive disease– Lesion progression 20% per year.– Renal atrophy 10% per year.– Artery occlusion 5% per year.

• RAS is a marker of increased cardiovascular mortality, predictors:– Older age– Impaired renal function– Bilateral RAS

Acute renal failure in patients with RASAcute renal failure in patients with RASAcute renal failure in patients with RASAcute renal failure in patients with RAS

• 1-14 days after the initiation of 1-14 days after the initiation of treatment with ACE inhibitors.treatment with ACE inhibitors.

• After the use of diuterics or other After the use of diuterics or other antihypertensive drugs.antihypertensive drugs.

• After major surgery.After major surgery.

• After the spontaneous progression After the spontaneous progression of RAS to total occlusion.of RAS to total occlusion.

• 1-14 days after the initiation of 1-14 days after the initiation of treatment with ACE inhibitors.treatment with ACE inhibitors.

• After the use of diuterics or other After the use of diuterics or other antihypertensive drugs.antihypertensive drugs.

• After major surgery.After major surgery.

• After the spontaneous progression After the spontaneous progression of RAS to total occlusion.of RAS to total occlusion.

Results of revascularization for ischemic Results of revascularization for ischemic

nephropathynephropathy



• 32 patients with unexplained renal impairment and RAS were treated with renal artery stent.

• In 70% of the patients the renal function improved or stabilized (p<0.007).

• 32 patients with unexplained renal impairment and RAS were treated with renal artery stent.

• In 70% of the patients the renal function improved or stabilized (p<0.007).

Harden et al, Lancet

1997

Harden et al, Lancet

1997





• 33 patients with bilateral RAS or RAS in 33 patients with bilateral RAS or RAS in solitary kidney.solitary kidney.

• Follow up: 20±11 months.Follow up: 20±11 months.

• Significant improvement in 72%; mild Significant improvement in 72%; mild improvement in 28%.improvement in 28%.

• Preservation of renal size in all patients.Preservation of renal size in all patients.

• 33 patients with bilateral RAS or RAS in 33 patients with bilateral RAS or RAS in solitary kidney.solitary kidney.

• Follow up: 20±11 months.Follow up: 20±11 months.

• Significant improvement in 72%; mild Significant improvement in 72%; mild improvement in 28%.improvement in 28%.

• Preservation of renal size in all patients.Preservation of renal size in all patients.

Watson et al. Circulation 2000Watson et al. Circulation 2000

Signs that a patient with ischemic nephropathy Signs that a patient with ischemic nephropathy

will benefit from revascularizationwill benefit from revascularization

Signs that a patient with ischemic nephropathy Signs that a patient with ischemic nephropathy

will benefit from revascularizationwill 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)*

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)*

• *Uder M, Huke U CVIR 2005*Uder M, Huke U CVIR 2005• *Uder M, Huke U CVIR 2005*Uder M, Huke U CVIR 2005

Percutaneous Percutaneous

revascularizationrevascularization

Percutaneous Percutaneous

revascularizationrevascularization• Technical success:98-100%Technical success:98-100%

• Long term patency rate 85%-98%Long term patency rate 85%-98%

• Complications:Complications:

– Mortality 1-3%Mortality 1-3%

– Major complications: 3-5%Major complications: 3-5%

– Minor complications 10-20%Minor complications 10-20%

• Technical success:98-100%Technical success:98-100%

• Long term patency rate 85%-98%Long term patency rate 85%-98%

• Complications:Complications:

– Mortality 1-3%Mortality 1-3%

– Major complications: 3-5%Major complications: 3-5%

– Minor complications 10-20%Minor complications 10-20%

An analysis of the pooled results of

studies of

conventional balloon angioplasty in

1118

patients

An analysis of the pooled results of

studies of

conventional balloon angioplasty in

1118

patients

• Hospital death 0.5%

• Nephrectomy 0.3%

• Renal surgery 2%

• Occlusion of a side branch of the renal artery 2.2%

• Cholesterol embolization 1.1%

• Injury at the site of vascular access 2.3%

• Hospital death 0.5%

• Nephrectomy 0.3%

• Renal surgery 2%

• Occlusion of a side branch of the renal artery 2.2%

• Cholesterol embolization 1.1%

• 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

EvidenceEvidenceEvidenceEvidence

3 randomized controlled trials compared medical treatment to percutaneous renal

revascularization:

• DRASTIC: Dutch Renal Artery Stenosis Intervention Cooperative Study Group

• EMMA: Essai Multicentrique Medicaments vs Angioplastie Study Group

• SNRASCG: Scottish and Newcastle Renal Artery Stenosis Collaborative Group

3 randomized controlled trials compared medical treatment to percutaneous renal

revascularization:

• DRASTIC: Dutch Renal Artery Stenosis Intervention Cooperative Study Group

• EMMA: Essai Multicentrique Medicaments vs Angioplastie Study Group

• SNRASCG: Scottish and Newcastle Renal Artery Stenosis Collaborative Group

Systolic and Diastolic BPSystolic 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)


•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 AgentsNumber of Antihypertensive Agents


•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


•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


Meta-analysis PTRA vs MedicaMeta-analysis PTRA vs Medical treatmentl treatmentIves et al. Nephrol Dial Transplant 2003Ives et al. Nephrol Dial Transplant 2003

Nordmann et al. Am J Med 2003Nordmann et al. Am J Med 2003

Meta-analysis PTRA vs MedicaMeta-analysis PTRA vs Medical treatmentl treatmentIves et al. Nephrol Dial Transplant 2003Ives et al. Nephrol Dial Transplant 2003


Change in blood pressure

Renal functionRenal function

No significant difference in serum creatinine or creatinine clearance between the two groups in any of the trials.

No significant difference in serum creatinine or creatinine clearance between the two groups in any of the trials.


Meta-analysis PTRA vs MedicatieMeta-analysis PTRA vs Medicatie Ives et al. Nephrol Dial Transplant 2003Ives et al. Nephrol Dial Transplant 2003


Meta-analysis PTRA vs MedicatieMeta-analysis PTRA vs Medicatie Ives et al. Nephrol Dial Transplant 2003Ives et al. Nephrol Dial Transplant 2003


Change in renal function

Cardiovascular and

Renovascular Complications

Cardiovascular and

Renovascular Complications

In all studies, the risk of cardiovascular and In all studies, the risk of cardiovascular and renovascular complications were lower in the renovascular complications were lower in the

PTA vs. Medical treatment group (9.6% PTA vs. Medical treatment group (9.6% vs24.5%)vs24.5%)

••Cardiovascular complications (myocardial infarction, angina, heart failure, stroke, Cardiovascular complications (myocardial infarction, angina, heart failure, stroke, non-procedure-related symptomatic hypotension, or cardiovascular death)non-procedure-related symptomatic hypotension, or cardiovascular death)

••Renovascular complications (defined as an increase of serum creatinine of more than Renovascular complications (defined as an increase of serum creatinine of more than 50 per cent, cholesterol embolisation, development of renal failure, total occlusion 50 per cent, cholesterol embolisation, development of renal failure, total occlusion

of the stenotic artery, dissection of the renal artery, major complication during of the stenotic artery, dissection of the renal artery, major complication during balloon angioplasty other than Haematoma at the puncture site, or need for balloon angioplasty other than Haematoma at the puncture site, or need for

dialysis)dialysis)

In all studies, the risk of cardiovascular and In all studies, the risk of cardiovascular and renovascular complications were lower in the renovascular complications were lower in the

PTA vs. Medical treatment group (9.6% PTA vs. Medical treatment group (9.6% vs24.5%)vs24.5%)

••Cardiovascular complications (myocardial infarction, angina, heart failure, stroke, Cardiovascular complications (myocardial infarction, angina, heart failure, stroke, non-procedure-related symptomatic hypotension, or cardiovascular death)non-procedure-related symptomatic hypotension, or cardiovascular death)

••Renovascular complications (defined as an increase of serum creatinine of more than Renovascular complications (defined as an increase of serum creatinine of more than 50 per cent, cholesterol embolisation, development of renal failure, total occlusion 50 per cent, cholesterol embolisation, development of renal failure, total occlusion

of the stenotic artery, dissection of the renal artery, major complication during of the stenotic artery, dissection of the renal artery, major complication during balloon angioplasty other than Haematoma at the puncture site, or need for balloon angioplasty other than Haematoma at the puncture site, or need for

dialysis)dialysis)

ConclusionsConclusions

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.

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 StentPTA vs StentPTA vs StentPTA vs Stent

• 85 patients with ostial RAS.85 patients with ostial RAS.• Intention-to-treat analysis.Intention-to-treat analysis.• Inclusion:Inclusion:

– RAS>50%RAS>50%– HTNHTN– Positive captopril renography OR increase Cr after Positive captopril renography OR increase Cr after

ACE-IACE-I• Exclusion: Exclusion:

– Renal size < 8cmRenal size < 8cm– <25% renal function by renography<25% renal function by renography

• 85 patients with ostial RAS.85 patients with ostial RAS.• Intention-to-treat analysis.Intention-to-treat analysis.• Inclusion:Inclusion:

– RAS>50%RAS>50%– HTNHTN– Positive captopril renography OR increase Cr after Positive captopril renography OR increase Cr after

ACE-IACE-I• Exclusion: Exclusion:

– Renal size < 8cmRenal size < 8cm– <25% renal function by renography<25% renal function by renography

van de Ven et al. Lancet 1999van de Ven et al. Lancet 1999

Cum

ulat

ive

pri

ma

ry p

ate

ncy

(%)

Time after procedure (months)

0 1 2 3 4 5 60

20

40

60

80

100

Stent

PTRA

42

42

37

24

37

23

36

21

36

21

35

21

30

12

35

21

Stent

Angioplasty

p < 0.001

Cumulative primary patency

PTRA versus StentPTRA versus Stentvan de Ven et al. Lancet 1999van de Ven et al. Lancet 1999


49%57%

80% 77%

0%

20%

40%

60%

80%

100%

Cure / improved Improved / stable

PTRA

Stent

49%57%

80% 77%

0%

20%

40%

60%

80%

100%

Cure / improved Improved / stable

PTRA

Stent

Blood pressure Renal function



“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 end-stage disease”.

“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 end-stage 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!

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!

AAngioplastyngioplasty andand S Stenttent forfor

RRenalenal A Arterialrterial L Lesionsesions

AAngioplastyngioplasty andand S Stenttent forfor

RRenalenal A Arterialrterial L Lesionsesions

• Multicenter Randomized clinical trial.Multicenter Randomized clinical trial.

• Approx 1000 pts will be randomized to Approx 1000 pts will be randomized to optimal medical therapy or to stenting optimal medical therapy or to stenting with optimal medical therapywith optimal medical therapy

• Multicenter Randomized clinical trial.Multicenter Randomized clinical trial.

• Approx 1000 pts will be randomized to Approx 1000 pts will be randomized to optimal medical therapy or to stenting optimal medical therapy or to stenting with optimal medical therapywith 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 medical-therapy 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.

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 medical-therapy 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 2009Volume 361:1953-1962 November 2009

The ASTRAL Investigators. N Engl J Med 2009;361:1953-1962

Renal Function in Patients with Renal-Artery Stenosis Treated with Revascularization or Medical Therapy Alone


Kaplan-Meier Curves for the Time to the First Renal and Cardiovascular Events


Kaplan-Meier Curves for Overall Survival


Systolic and Diastolic Blood Pressure

Last question: why does renal function Last question: why does renal function

may deteriorate after revascularization?may deteriorate after revascularization?

Last question: why does renal function Last question: why does renal function

may deteriorate after revascularization?may deteriorate after revascularization?

1.1. Contrast nephropathy.Contrast nephropathy.

2.2. Cholesterol embolization.Cholesterol embolization.

3.3. Exposure of diseased glomeruli to high Exposure of diseased glomeruli to high blood pressure.blood pressure.

1.1. Contrast nephropathy.Contrast nephropathy.

2.2. Cholesterol embolization.Cholesterol embolization.

3.3. Exposure of diseased glomeruli to high Exposure of diseased glomeruli to high blood pressure.blood pressure.

Is there any role for distal Is there any role for distal

protection? protection?

Is there any role for distal Is there any role for distal

protection? protection?

• 65 hypertensive patients with significant RAS were stented with distal protection.

• 2 protection devices were used:

– Guardwire: 2 sizes [2.5-5mm and 3-6 mm]

– Filterwire: 3.5-5.5 mm]

• 65 hypertensive patients with significant RAS were stented with distal protection.

• 2 protection devices were used:

– Guardwire: 2 sizes [2.5-5mm and 3-6 mm]

– Filterwire: 3.5-5.5 mm]• Henry et al. Cath and cardio interv 2003Henry et al. Cath and cardio interv 2003• Henry et al. Cath and cardio interv 2003Henry et al. Cath and cardio interv 2003

ResultsResultsResultsResults

• ASA and plavix for 4 weeks.ASA and plavix for 4 weeks.

• Follow up: average 22 months; DSA if Follow up: average 22 months; DSA if restenosis suspected by US.restenosis suspected by US.

• Cr improved or stabilized in ALL patients.Cr improved or stabilized in ALL patients.

• The patients with moderate to severe The patients with moderate to severe renal impairment benefited the most.renal impairment benefited the most.

• Blood pressure control in all.Blood pressure control in all.

• ASA and plavix for 4 weeks.ASA and plavix for 4 weeks.

• Follow up: average 22 months; DSA if Follow up: average 22 months; DSA if restenosis suspected by US.restenosis suspected by US.

• Cr improved or stabilized in ALL patients.Cr improved or stabilized in ALL patients.

• The patients with moderate to severe The patients with moderate to severe renal impairment benefited the most.renal impairment benefited the most.

• Blood pressure control in all.Blood pressure control in all.

Distal protection devicesDistal protection devicesDistal protection devicesDistal protection devices

• Visible debris in filter Visible debris in filter in all cases.in all cases.

• Atheromatous Atheromatous plaques, necrotic plaques, necrotic cores, thrombi, cores, thrombi, macrophages.macrophages.

• Visible debris in filter Visible debris in filter in all cases.in all cases.

• Atheromatous Atheromatous plaques, necrotic plaques, necrotic cores, thrombi, cores, thrombi, macrophages.macrophages.

Indications for revascularization

of RAS

Indications for revascularization

of RAS1. Hypertensive control.1. Reasonable likelihood of cure.

1. Onset before age 30.

2. Recent onset after age 60.

3. 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.

1. Hypertensive control.1. Reasonable likelihood of cure.

1. Onset before age 30.

2. Recent onset after age 60.

3. 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.

IndicationsIndications2. 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 syndrome1. Flash pulmonary edema.

2. Unstable angina.

3. Worsening of CHF.

2. Renal salvage1. 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 syndrome1. Flash pulmonary edema.

2. Unstable angina.

3. Worsening of CHF.

Case #1

S/p EVAR new onset of HTN

Case #1

S/p EVAR new onset of HTN

Case # 2Case # 2

• 50-year-old male with solitary kidney.

• Smoker.

• Refractory HTN.

• Cr: 3.8 mg/dl

• 50-year-old male with solitary kidney.

• Smoker.

• Refractory HTN.

• Cr: 3.8 mg/dl

• B/P: 160/80 mmHg

• Cr: 1.8 mg/dl

• B/P: 160/80 mmHg

• Cr: 1.8 mg/dl

The patient was re-admitted 18 months later with Cr: 2.8 mg/dl, and BP: 180/90 mmHg.

The patient was re-admitted 18 months later with Cr: 2.8 mg/dl, and BP: 180/90 mmHg.

ConclusionsConclusions• Incidental RAS is not an indication for Incidental RAS is not an indication for

revascularization.revascularization.

• Hypertensive patients with RAS may Hypertensive patients with RAS may benefit from revascularization if HTN is benefit from revascularization if HTN is “refractory” to medical treatment.“refractory” to medical treatment.

• Revascularization is indicated in Revascularization is indicated in hypertensive patients with RAS if renal hypertensive patients with RAS if renal mass loss or renal function decline is mass loss or renal function decline is observed during hypertensive treatment.observed during hypertensive treatment.

• Incidental RAS is not an indication for Incidental RAS is not an indication for revascularization.revascularization.

• Hypertensive patients with RAS may Hypertensive patients with RAS may benefit from revascularization if HTN is benefit from revascularization if HTN is “refractory” to medical treatment.“refractory” to medical treatment.

• Revascularization is indicated in Revascularization is indicated in hypertensive patients with RAS if renal hypertensive patients with RAS if renal mass loss or renal function decline is mass loss or renal function decline is observed during hypertensive treatment.observed during hypertensive treatment.

Controversies in renal arterial interventions. ACHILLES CHATZIIOANNOU, MD Assoc. Professor of...

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Transcript of Controversies in renal arterial interventions. ACHILLES CHATZIIOANNOU, MD Assoc. Professor of...