CORAL Trial Aftermath: What Do We Do Now? Renal … · – Ekos Corporation (DSMB) – Medtronic...
Transcript of CORAL Trial Aftermath: What Do We Do Now? Renal … · – Ekos Corporation (DSMB) – Medtronic...
CORAL Trial Aftermath:
What Do We Do Now?
Renal Revascularization in Perspective
Michael R. Jaff, DO
Massachusetts General Hospital
Boston, Massachusetts, USA
Michael R. Jaff, DO
Conflicts of Interest
2
• Consultant
– Abbott Vascular (non-compensated)
– Boston Scientific (non-compensated)
– Cardinal Health
– Cordis Corporation (non-compensated)
– Covidien (non-compensated)
– Ekos Corporation (DSMB)
– Medtronic (non-compensated)
– Micell, Inc
– Primacea
• Equity
– Access Closure, Inc
– Icon Interventional, Inc
– I.C.Sciences, Inc
– Janacare, Inc
– MC10
– Northwind Medical, Inc.
– PQ Bypass, Inc
– Primacea
– Sano V, Inc.
– Vascular Therapies, Inc
• Board Member
– VIVA Physicians (Not For Profit
501(c) 3 Organization)
• www.vivapvd.com
• CBSET
January 2015
Prevalence of Atherosclerotic RAS at Cardiac
Catheterization
White, et al. Circ. 2006;114:1892-1895.
Study, Year n ARAS >30%
(%)
ARAS >50%
(%) Bilateral (%)
Vetrovec et al, 1989 116 29% 23% 29%
Harding et al, 1992 1302 29% 15% 28%
Jean et al, 1994 196 33% 18% -
Rihal et al, 2002 297 34% 19% 19%
Weber-Mzell et al, 2002 177 25% 11% 26%
The Mechanisms of Renovascular
Hypertension Have Been Well Described
Garovic, VD, et al. Circ. 2005;112:1362-1374.
Relation Between Renal Artery Stenosis,
Hypertension, and Chronic Renal Failure
Safian, et al. N Engl J Med. 2001;344:410.
Do You Think These Patients with ARAS and
These Scenarios Warrant Intervention?
• Dialysis-dependent renal failure
• Chronic renal insufficiency
• Refractory/resistant hypertension
• Cardiac disturbance syndrome
• Need for use of ACEI/ARB
• Unilateral renal artery stenosis
Methods
• Open-label, randomized, international, multicenter
controlled clinical trial
• All received medical therapy:
– BP, diabetes, and lipids to goal, with participants
provided free:
• Candesartan ± hydrochlorothiazide (Atacand®)
• Atorvastatin + Amlodipine (Caduet®)
– Antiplatelet therapy
N Engl J Med. 2014;370:13-22.
Inclusion Criteria
Clinical syndrome:
• Hypertension ≥2 anti-hypertensive medications, OR
• Renal dysfunction defined as Stage 3 or greater CKD
-AND-
Atherosclerotic renal artery stenosis:
• Angiographic: ≥60% and <100%, OR
• Duplex: systolic velocity of >300 cm/sec, OR
• Core lab approved MRA, OR
• Core lab approved CTA N Engl J Med. 2014;370:13-22.
Primary Endpoint
• Composite of major cardiovascular or renal events:
– Cardiovascular or renal death
– Stroke
– Myocardial infarction
– Heart failure hospitalization
– Progressive renal insufficiency
– Permanent renal replacement therapy
N Engl J Med. 2014;370:13-22.
Baseline Characteristics
• No significant
differences in clinical
and angiography
characteristics
• Approximately 20%
global ischemia
• Stenosis severity
similar to FDA
approval trials1-3
1. Rocha-Singh K, et al. ASPIRE-2. JACC. 2005;46:776-83.
2. Rocha-Singh K, et al. RENAISSANCE. CCI. 2008;72:853-62.
3. Jaff MR, et al. HERCULES. CCI. 2012;80:343-50.
N Engl J Med. 2014;370:13-22.
Age (years)
White race (%)
69.3 ± 9.4 69.0 ± 9.0
Characteristic Stent + Medical Medical
51.0 48.9
91.5 90.9
Male gender (%)
Black race (%)
Body mass index (kg/m2)
Systolic blood pressure (mmHg)
Estimate GFR (ml/minute)
Medical history and risk factors (%)
Diabetes
Prior myocardial infarction
History of heart failure
Smoking in past year
Angiography
% stenosis (core lab)
% stenosis (investigator)
7.0 7.0
28.2 ± 5.3 28.7 ± 5.7
149 ± 23.2 150.4 ± 23.0
58.0 ± 23.4 57.4 ± 21.7
32.4 34.3
26.5 30.2
12.0 15.1
28.0 32.2
67.3 ± 11.4 66.9 ± 11.9
72.5 ± 14.6 74.3 ± 13.1
N = 459 N = 472
Baseline Characteristics of the Study Population According to Treatment Group
Global ischemia (%) 20.0 16.2
Bilateral disease (%) 22.0 18.1
Results: Periprocedural Clinical
Complications
• No participant required dialysis within 30 days of
randomization
• 1/459 (0.2%) in-stent + medical therapy initiated
dialysis between 30 and 90 days after
randomization
• 1 stroke resulting in death, day of randomization,
Medical Therapy Only group.
N Engl J Med. 2014;370:13-22.
Who Was Excluded from CORAL?
• Nonatherosclerotic causes (ie, FMD)
• CKD with serum creatinine >4.0 mg/dL
• Kidney length <7.0 cm
• Lesion requiring more than a single stent
• Hospitalization for CHF within 30 days
• In-stent restenosis
• Contralateral renal artery intervention within past
9 months
Study Overview
• Patient-level data from 901 patients (117 centers) in 5
prospective multicenter FDA-approved IDE studies of renal
artery stent revascularization was pooled
• Associations of BP reduction were determined by logistic
regression
Catheter Cardiovasc Intervent. 2014;83:603-9.
Included studies
Study Device Number of Subjects Selected Inclusion Criteria
HERCULES RX Herculink
Elite
202 Uncontrolled BP and suboptimal
PTA
SOAR Bridge TM balloon
expandable stent
186 Uncontrolled BP and failed PTA
RENAISSANCE Express ® SD
Renal
Premounted
Stent System
100 Uncontrolled BP and suboptimal
PTA, renal dysfunction (Cre<3.0
mg/dL), recurrent ‘‘flash’’
pulmonary edema,
or any combination thereof
RESTORE ParaMount™ XS
DoubleStrut™
balloon
expandable stent
205 Severe HTN
ASPIRE Palmaz Balloon
expandable stent
208 Uncontrolled BP and suboptimal
PTA
Catheter Cardiovasc Intervent. 2014;83:603-9.
Blood Pressure Response
Catheter Cardiovasc Intervent. 2014;83:603-9.
164
79
146
76
020406080
100120140160180
Systolic BP Diastolic BP
Blo
od
Pre
ssu
re (
mm
Hg
)
Pre Post
p<0.0001
p<0.0001
Results of Multivariable Logistic Regression Models Testing Clinical
Variables Associated with BP Response
Predictor Odds Ratio (95% CI) P Value
Clinical variables
Baseline systolic blood pressure,
10 mmHg increase
1.76 (1.53-2.03) <0.0001
Baseline diastolic blood pressure,
10 mmHg increase
1.09 (0.92-1.30) 0.32
Catheter Cardiovasc Intervent. 2014;83:603-9.
So, What Do We Know?
• Atherosclerotic renal artery stenosis is common
• It connotes bad outcomes, even worse than in
those patients with coronary artery disease alone
• Optimal medical therapy is generally all you need
for CORAL-eligible patients
• There is undoubtedly a population of patients who
need renal artery intervention
– ie, cardiac disturbance syndromes
• The future of reimbursement for renal artery
stenting is very murky
Rich Educational Content…Beyond the Meeting
www.VIVA365.org
The Global Education Course for Vascular Medicine and Intervention
November 2-5, 2015 Wynn Las Vegas
www.VIVAPhysicians.org