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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%

Atherosclerotic RAS Is Bad…

Arch Intern Med. 2005;165:207.

Cardiovascular Mortality

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

N Engl J Med. 2014;370:13-22.

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.

Primary Endpoint

N Engl J Med. 2014;370:13-22.

Results: Subgroups

P Value for Interaction Stent vs Medical Therapy

Results: Systolic Blood Pressure

p = 0.03

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


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


PTA


Blood Pressure Response


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


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

PSV 273 cm/sec Lt Kidney 10.2 cm

PSV 286 cm/sec Lt Kidney 8.8 cm

6/5/12

7/15/14

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

CORAL Trial Aftermath:

What Do We Do Now?

Renal Revascularization in Perspective

Michael R. Jaff, DO

Massachusetts General Hospital

Boston, Massachusetts, USA

coral trial aftermath: what do we do now? renal … · – ekos corporation (dsmb) – medtronic...

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