SVS Clinical Research Priorities
Mesenteric/Renal
Kimberley J. Hansen, MD
ACE inhibitor Rx
Calcium Blockers
PTRA introduced
Cooperative study of
renovascular hypertension
Improved surgery
Small, randomized trials
Urgent bilateral nephrectomy for
treatment resistant, malignant HTN
Med Rx vs PTRA
Prospective trials:
Med Rx vs Stent
Therapy
CORAL
ASTRAL
STAR
RAVE
Function tests:
Blood flow, sodium excretion
Renal artery
clip
hypertension
1930
Surgery for renal
reconstruction
1940
Nephrectomy
for
hypertension
with a small
kidney
Wake Forest Baptist Health
1950
1960
Early imaging:
intravenous
pyelography
scan
1970
1980
1990
2000
ARB Rx
Advanced
imaging:
MRA, CTA
Statin therapy
Stents
ACE inhibitor Rx
Calcium Blockers
PTRA introduced
Cooperative study of
renovascular hypertension
Improved surgery
Small, randomized trials
Urgent bilateral nephrectomy for
treatment resistant, malignant HTN
Med Rx vs PTRA
Prospective trials:
Med Rx vs Stent
Therapy
CORAL
ASTRAL
STAR
RAVE
Function tests:
Blood flow, sodium excretion
Renal artery
clip
hypertension
1930
Surgery for renal
reconstruction
1940
Nephrectomy
for
hypertension
with a small
kidney
Wake Forest Baptist Health
1950
1960
Early imaging:
intravenous
pyelography
scan
1970
1980
1990
2000
ARB Rx
Advanced
imaging:
MRA, CTA
Statin therapy
Stents
Prevalence of Renovascular Lesions
• CHS Participants > 65 years
• Patients – Coronary Arteriography
6-7%
6-18%
• Patients – Aortography
16-40%
• ‘NEW’ Hypertensives > 60 years
20-30%
DBP > 110/mmHg
J Vasc Surg 2002;36:443-451, Am Heart J 1998,136:913-918, Cathet Cardiovasc Diagn 1994;32:8-10, J Am Soc Nephrol 1992;2:1608-1616,
Am J Med 1990;88:46N-51N, Ann Vasc Surg 1998;12:17-22, J Vasc Surg 1993;18:433-440, Am J Med 2000;109:642-647, J Am Hypertension 1996;10:83-85,
Am J Med 1994;96:10-14, Int Angiol 1992;11:195-199
Wake Forest Baptist Health
CMS PTRA-S
Procedures
Renal Angioplasty
Renal Stent
Both Renal Angioplasty and Stent
Total, 5% file
Extrapolated to 100%
1996
189
61
133
383
7,660
1998
192
120
258
570
11,400
2000
219
287
420
926
18,520
Note. - Procedure totals are from 5% files for analysis of codes 35471, 37205, and both, respectively. Results from
the 5% Part B files were multiplied by 20 to yield “extrapolated to 100%” totals.
AJR 2004; 183:561-568
Wake Forest Baptist Health
PTRA-S per 100,000
CMS Region
Keystone
Southeast
South
Great Lakes
Pacific
Southwest
Great Western
Other
Mid-Atlantic
North East
National
1996
1998
2000
% Increasea
12
22
30
25
14
32
38
5
38
18
25
26
41
46
40
30
53
39
14
45
19
38
57
86
87
62
31
71
70
9
62
26
61
482
387
287
253
228
223
186
178
166
142
239
Note. - Overall utilization pooled for all regions is listed in the last row (these numbers differ slightly from the average of each region because of slight
differences in number of beneficiaries among regions, particularly the low-utilization, sparsely populated “other” region). Average utilization in 2000
ranged from 26 to 87 per 100,000 (excluding “other”). CMS regions are Mid-Atlantic: DE, DC, IN, MD, OH, VA, WV; Southwest: AR, CO, LA, NM, OK, TX;
Northeast: CT, ME, MA, NH, NY, RI, VT; Great Lakes: IL, IA, MI, MN, WI; Great Western: AK, ID, KS, MO, MT, NE, ND, OR, SD, UT, WA, WY; Keystone: NJ, PA;
Southeast: AL, KY, MS, NC, SC, TN; South: FL, GA Pacific: AZ, CA, HI, NV; Other: Puerto Rico, Virgin Island. CMS = Centers for Medicare and Medicaid
Services.
aGrowth in annual procedure volume when compairing 2000 with 1996
AJR 2004; 183:561-568
Wake Forest Baptist Health
Annual PTRA-S Volume
Physician Specialty
1996 (%)
1998 (%)
2000 (%)
% of Increasea
Cardiology
Radiology
Surgery
Other
2,380 (31)
4,700 (61)
300 (4)
280 (4)
5,060 (44)
5,380 (61)
480 (4)
480 (4)
9,220 (50)
7,660 (41)
760 (4)
880 (5)
287
63
153
214
7,660
11,400
18,520
142
Total
Note. - Physicians identifying their specialty as cardiology or internal medicine are considered cardiologists in this table,
those reporting their specialty as interventional radiology or radiology are identified as radiologists, and those reporting
their specialty as vascular surgery or general surgery are categorized as surgeons. These specialties accounted for more
than 95% of providers submitting claims for renal artery interventional procedures for each year.
aGrowth
in annual procedure volume when comparing 2000 with 1996
AJR 2004; 183:561-568
Wake Forest Baptist Health
Frequency of PTRA-S 2005
National Inpatient Sample
Region
South
Northeast
Midwest
West
Totals
Overall Weighted
%
Frequency (SD) Hospitalization
Empirical
RA-PTAS
Prophylactic
RA-PTAS
30,457 (2,484)
15,300 (1,847)
17,955 (1,634)
12,221 (1,393)
0.20
0.20
0.20
0.16
23,635
11,055
13,548
9,049
6,822
4,245
4,407
3,172
75,933
--
57,287
18,646
Estimated Health Cost Expenditure – 75,933 x (5,136 + 723)  444,891,447
Source: National Inpatient Sample
(Unpublished)
Wake Forest Baptist Health
2007 MedCAC Voting Questions
Highly Confident (5) – Not Confident (1)
1. For the treatment of patients with atherosclerotic RAS, how
confident are you that the evidence is adequate to draw
conclusions about safety and clinical effectiveness of the following
renal artery interventions:
Overall Average
a)
b)
c)
d)
Surgical renal artery reconstruction (RAR)?
PTRA without stent placement?
PTRAS with bare metal stents?
PTRAS with drug-eluting stents?
Wake Forest Baptist Health
2.92
2.92
2.85
1.00
2007 MedCAC Voting Questions
Highly Confident (5) – Not Confident (1)
2. Based on the evidence presented, how confident are you that the
published results apply to :
Overall Average
a) Medicare patients with typical
comorbidities?
b) Providers (facilities/physicians) in
community practice?
Wake Forest Baptist Health
3.69
2.15
2007 MedCAC Voting Questions
Highly Confident (5) – Not Confident (1)
3. Based on the evidence presented for patients with atherosclerotic
RAS, how confident are you that compared to aggressive medical
treatment alone there are improved key health outcomes
attributable to the following co-interventions:
Overall Average
a)
b)
c)
d)
Surgical renal artery reconstruction (RAR)?
PTRA without stent placement?
PTRAS with bare metal stents?
PTRAS with drug-eluting stents?
Wake Forest Baptist Health
2.31
2.08
3.15
N/A
2007 MedCAC Voting Questions
Strongly Agree(1) – Strong Disagree(5)
4. Based on the evidence presented, should Medicare national
coverage of any non-medical treatments for atherosclerotic RAS be
limited only to patients enrolled in qualified clinical research
studies?
Overall Average
2.23
Wake Forest Baptist Health
Prospective Randomized Clinical Trials
PTRA versus Open Repair
• Single center, Malmö
• Inclusion
< 70 years
No diabetes
Hypertension with unilateral RA stenosis
• RVH defined by RVRA’s
• GFR estimated by Cr-EDTA clearance
• Angiographic follow-up for all
• PTRA primary/secondary patency 75%/90%
Surgical 96%/97%
• PTRA HTN cured/improved 83%
Surgical 89%
• Non-representative patient cohort
Significant difference baseline GFR
PTRA crossover to surgery
• No Endoluminal stents
J Vasc Surg 1993;18:841-850
Wake Forest Baptist Health
Early Prospective Randomized Trials
Trial
Patients
(n)
Unilateral or
Bilateral Disease
Randomized
Treatment
Duration of
Follow-Up
Main Endpoints
Webster
et al
SNRASCO
55
Unilateral and
bilateral, but
two groups
analyzed
separately
Angioplasty v
medical
management
Patients reviewed at
end of 4-week run-in
period (baseline) then
at 1, 3, and 6 months,
then at 6-month
intervals
Primary: BP and SCr
at 6 months and the
change in these from
baseline
Plouin et al
EMMA
49
Unilateral only
Angioplasty (with
or without stent
insertion) v medical
management
Patients reviewed at
end of 2-6 week runin period (baseline)
then at 6 months
Primary: BP at
termination* and the
change from baseline
Secondary: treatment
score and incidence
of complications
van Jaarsveld
et al
DRASTIC
106
Unilateral and
Bilateral
Angioplasty
v medical
management
Patients reviewed
every 1-3 months,
and always at 3 and
12 months
Primary: BP at 3 and
12 months
Secondary: treatment
score, SCr, SCr
clearance, patency,
and incidence of
complications
From Ives NJ, Wheatley K, Stowe RL, et al: Continuing uncertainty about the value of percutaneous revascularization in atherosclerotic
renovascular disease: a meta-analysis of randomized trials. Nephrol Dial Transplant 2003;18:298-304 adapted with permission.
*Termination defined as 6 months after randomization or earlier in cases of refractory hypertension (diastolic blood pressure > 1 to 4 mm/Hg
despite maximal tolerated antihypertensive regimen. In such cases, blood pressure, treatment score, and SCr were determined prior to renal
arteriograph.
Nephrol Dial Transplant 2003;18:298-304
Wake Forest Baptist Health
Prospective Randomized Clinical Trials
STAR Study
• STent placement and blood pressure and lipid-lowering for prevention of
progression of renal dysfunction caused by Atherosclerotic ostial stenosis
of the Renal artery (Netherlands)
• Stenting versus angioplasty alone for ostial RAS
• Primary ‘Technical’ Success
Stent 88%
PTRA 57%
• Restenosis Rate
Stent 14%
PTRA 48%
• Primary endpoint: <20% Decline EFGR
No difference
• Secondary endpoints: HTN, heart and vascular events, mortality
No difference
• ESRD or mortality in 10% patients
J Nephrol 2003;16:807-812
Wake Forest Baptist Health
Management Of Renovascular Disease
Ongoing Randomized Controlled Trails
•Angiopolasty and STent for Renal Artery Lesions (ASTRAL –
United Kingdom)
•Renal Atherosclerotic ReVascularization Evaluation (RAVE –
Canada)
•Nephrology Ischemic ThERapy (NITER – Italy)
•Renal Artery Stenting in HemoDynamic Atherosclerotic Renal
Artery Stenosis (RADAR) – Europe and South America
•Cardiovascular Outcomes in Renal Atherosclerotic Lesions
(CORAL – United States, Canada, Australia, and New Zealand
Prospective Randomized Clinical Trials
ASTRAL Trial
• Angioplasty and STenting For Renal Artery Lesions
• Multicenter: 53 UK, 4 Australia
• PTRA-S versus Best Medical Management
(Statins, Antiplatelet, Antihypertension THX)
• 806 Patients (403 in each group); ‘Uncertain Worth’
• Mean follow up: 33.6 months (all 12 months)
Mean degree RAS: 76% diameter reduction
60% > 70% stenosis
• Primary endpoint: rate of change EGFR
• Secondary endpoints: HTN, heart and vascular events, mortality
• No difference in 1o or 2o endpoints
N Engl J Med 2009;361:1953-1962
Wake Forest Baptist Health
Prospective Randomized Clinical Trials
CORAL Trial
• Cardiovascular Outcomes in Renal Atherosclerotic Lesions
• Multicenter: Enrolled 1050 patients (U.S., Canada, Australia, New
Zealand)
• PTRA-S versus Best Medical Management
• Primary endpoint: composite CV mortality, MI, CHF, CVA, Doubling SCr,
ESRD
• Secondary endpoints: all cause mortality, EGFR, restenosis,
microvascular function, BP control
• Renal artery stenoses measured PRIOR to randomization at angiography
• Translesional pressure gradients before and after randomization
• Distal embolic protection encouraged (complete balloon occlusion)
• Recruitment/randomization closed 2010
• Publication/presentation 1/2014 (C. Cooper)
Am Heart J 2006;152:59-66
Wake Forest Baptist Health
Atherosclerotic Renovascular Disease
Multivariate Analysis – Death or Dialysis
Variable
ß Coefficient
Hazard Ratio
95% C.I.
P Value
Pre-Op EGFR
-0.8555
0.43
0.34, 0.54
<0.001
Diabetes Mellitus
0.5313
2.14
1.15, 3.97
0.007
Prior CVA
0.4068
1.50
1.02, 2.22
0.042
Al-Occl
0.5078
1.66
1.19, 2.31
0.003
Pre-Op BP
-0.2329
0.79
0.67, 0.94
0.006
BP Cure
-0.6637
0.52
0.30, 0.88
0.014
EGFR No Change
0.9259
1.49
1.04, 2.13
0.028
EGFR Worse
0.1070
1.95
1.06, 3.61
0.032
J Vasc Surg 2002;35:236-245
Wake Forest Baptist Health
Management of Renovascular Disease
PTRA-S and Ischemic Nephropathy
Reference/Date
Rees CR (1991)
Kuhn FP (1991)
Joffre F (1992)
Hennequin LM (1994)
MacLeod M (1995)
van de Ven PJG (1995)
Dorros G (1995)
Henry M (1996)
Iannone LA (1996)
Harden PN (1997)
Blum U (1997)
Boisclair C (1997)
Rundback JH (1998)
Fiala LA (1998)
Dorros G (1998)
Tuttle KR (1998)
Gross CM (1998)
Henry M (1999)
Rodriguez-Lopez JA (1999)
van de Ven PJ (1999)
Baumgartner I (2000)
Giroux (2000)
Lederman (2001)
Bush (2001)
Zeller (2004)
Totals=
n/r: Not Reported
SCr: Serum Creatinine
Renal Dysfunction
(# Pts)
14
n/r
4
6
16
n/r
29
10
29
32
20
17
45
9
63
74
12
48
32
29
n/r
21
111
50
239
1017
Function response (%)
Improved Unchanged Worsened
36%
36%
29%
n/r
n/r
n/r
50%
50%
0%
20%
40%
40%
25%
75%
33%
58%
8%
28%
28%
45%
20%
80%
36%
46%
18%
35%
35%
29%
0%
100%
0%
41%
35%
24%
18%
53%
30%
0%
100%
0%
No change in mean SCr
16%
75%
9%
55%
27%
18%
29%
67%
2%
No change in mean SCr
17%
55%
28%
33%
42%
25%
24%
76%
8%
78%
14%
23%
51%
26%
34%
39%
27%
22%
56%
22%
HTN Response (%)
Cured
11%
22%
27%
7%
0%
0%
6%
18%
4%
n/r
16%
6%
n/r
1%
2%
0%
19%
13%
15%
n/r
10%
Improved
5%
34%
64%
93%
40%
73%
46%
57%
35%
n/r
62%
61%
n/r
53%
42%
46%
69%
61%
55%
43%
43%
53%
70%
n/r
46%
51%
Restenosis
Failed
36%
44%
9%
0%
60%
27%
48%
24%
61%
n/r
22%
33%
n/r
47%
57%
52%
31%
20%
32%
42%
57%
47%
30%
n/r
54%
39%
(%)
39%
17%
18%
27%
17%
13%
25%
9%
14%
13%
17%
0%
26%
65%
n/r
14%
13%
11%
26%
14%
28%
n/r
21%
n/r
n/r
19%
Chronic Mesenteric Ischemia
PTVA+S vs. Open Repair
Author
(Source)
Atkins1
(Single
Center)
Gupta2
(Review)
Oderich3
(Review)
Symptomatic
Relief
Morbidity
Mortality
10
Patency
(1 yr)
Open
Repair
90%
35%
2%
91%
7%
PTVA + S
87%
29%
3%
67%
25%
Open
Repair
94.4%
34.7%
4.5%
90.8%
22.4%
PTVA + S
87.8%
14.1%
4.1%
74.2%
21.7%
Open
Repair
94%
47%
7%
89%
7%
PTVA + S
89%
15%
3%
74%
25%
Method
Symptomatic
Recurrence
(1 yr)
J Vasc Surg 2007;45:1162-11711
J Endovasc Ther 2010;17:540-5492
Ann Vasc Surg 2009;23:700-7123
Wake Forest Baptist Health
Acute Mesenteric Ischemia
Percutaneous vs. Open Repair
Thrombotic - Embolic In-Hospital
Occlusion
Mortality
Thrombotic - Embolic
Mortality
Open Repair
36% - 64%
50%
83% - 33%
Percutaneous
Intervention
72% - 28%
39%
33% - 53%
J Vasc Surg 2011;53:698-705
Wake Forest Baptist Health
Atherosclerotic Renovascular Disease
Summary
• Severe Hypertension Key Clinical Characteristic Favoring
Presence of Renovascular Disease
• Improved Renal Function Key Postoperative Result Favoring
of Dialysis-free Survival
• Associations With Improved Renal Function
• Severe Associated Hypertension
• Bilateral Renovascular Disease With Bilateral
Reconstruction
• Rapidly Deteriorating Renal Function
• Test(s) Physiologic Significance/Response
Wake Forest Baptist Health