Antoine SAUGUET, MD

Clinique PASTEUR, Toulouse, FRANCE

Antoine SAUGUET Faculty disclosure I have no financial relationships to disclose.

INTRODUCTION

FIRST STEP OPTIMAL MEDICAL THERAPY

Blood control sometimes poorly achieved with

progressive loss of renal function

SECOND STEP IDENTIFICATION OF PATIENTS WHO

WOULD BENEFIT FROM THE STENTING

PROCEDURE

POOR CORRELATION OF ANGIOGRAPHIC IMAGES

AND HEMODYNAMIC SIGNIFICANCE

DEGREE OF RENAL ARTERIE STENOSIS THAT

JUSTIFIES STENTING IS UNKNOW

Need for new tools

RENAL ARTERY STENOSIS

66% 33% 1%

Atherosclerosis Fibromuscular

dysplasia Others

• anevrysmal

• Takayasu arteritis

• giant cells arteritis

• APLS

RENAL ARTERY STENOSIS ETIOLOGY

RENAL ARTERY

FIBROMUSCULAR DYSPLASIA

Non inflammatory disease Mostly young females (30-50y)

Multiples locations Severe symptomatic hypertension

STRINGS OF BEADS

Trinquart L, Mounier-Vehier C, Sapoval M, et al.

Efficacy of revascularization for renal artery stenosis caused by fibromuscular dysplasia:

a systematic review and meta- analysis. Hypertension 2010;56:525-32.

Baseline characteristics

Trinquart L, Mounier-Vehier C, Sapoval M, et al.

Efficacy of revascularization for renal artery stenosis caused by fibromuscular dysplasia:

a systematic review and meta- analysis. Hypertension 2010;56:525-32.

RENAL ARTERY

FIBROMUSCULAR DYSPLASIA

Blood pressure response to Renal angioplasty

All these blood pressure response are without treatment

INDICATION CLASS I LOE B

Uncontroled hypertension with mean baseline gradient > 20mmHg

Balloon angioplasty close to 100% success rate

less than 10% restenosis 10 years

Massoud A, et al JACC june 23, 2009:2363-71

PREDICTION OF HTA IMPROVEMENT AFTER STENTING OF RENAL ARTERY STENOSIS

N=62 50-90% RA stenosis

Translesionnal pressure gradient, IVUS, angiographics parameters

Hyperhemia systolic gradient > 21mmHg only independant

Predictor of HTA improvement

806 PATIENTS

ASTRAL STUDY

40% Intermediate

stenosis

Wheatley K, Ives N, Gray R et al. Revascularization versus medical therapy for renal-artery stenosis.

N Engl J Med 2009; 361: 1953–1962

Wheatley K, Ives N, Gray R et al. Revascularization versus medical therapy for renal-artery stenosis.

N Engl J Med 2009; 361: 1953–1962

5 years follow up

ASTRAL STUDY

5 years

follow up P=NS

Wheatley K, Ives N, Gray R et al. Revascularization versus medical therapy for renal-artery stenosis.

N Engl J Med 2009; 361: 1953–1962

ASTRAL STUDY

CRITICISMS OF ASTRAL

Inexperienced operators 8% serious complication

2patients/center/y 79% technical success

No core lab

Primary endpoint was rate of renal function decline (40% had normal or

near normal baseline renal function)

Selection bias toward enrolling asymptomatic patients with non-

obstructive RAS (unlikely to benefit)

Only about 40 to 50% of the patients were treated with drugs that block

the pathway of the renin angiotensin aldosterone system

40% of patients have less than 70% stenosis

17% did not get stenting in RAS arm

Stenting and Medical Therapy for Atherosclerotic Renal-Artery Stenosis

Cooper CJ et al. N Engl J Med 2014;370:13-22

CORAL STUDY Multicenter, open label randomized, controlled trial

Medical therapy alone vs MT + revascularization

Primary endpoint on clinical outcomes

INCLUSION CRITERIA

- TA> 155mmHg

- Systolic pressure gradient>20mmHg

- >80% <100% stenosis

Change during study SBP<155 inclusion

With normal BP, inclusion criteria on

Duplex echo, MRI

Stenting and Medical Therapy for Atherosclerotic Renal-Artery Stenosis

Cooper CJ et al. N Engl J Med 2014;370:13-22

CORAL STUDY

Stenting and Medical Therapy for Atherosclerotic Renal-Artery Stenosis

Cooper CJ et al. N Engl J Med 2014;370:13-22

5 YEARS

FOLLOW UP

LESS THAN 10% patient at 5y

CORAL STUDY

Results: Systolic Blood Pressure

P = 0.03

C. Cooper, AHA 2013 Stenting and Medical Therapy for Atherosclerotic Renal-Artery Stenosis

Cooper CJ et al. N Engl J Med 2014;370:13-22

SIGNIFICANT REDUCTION OF 2mmHg in SBP with stenting

CORAL STUDY

CRITICISMS WITH CORAL

Endpoints changed during the trial and very few patients remained for 5 years...Is this long enough for clinical endpoints evaluation?

Use of embolic protection device complicated the procedure and changed during the trial.

Patients with only 60% RAS were included in the trial.

A large number of screened patients were not enrolled in the trial suggesting an enrollment bias.

Stenting and Medical Therapy for Atherosclerotic Renal-Artery Stenosis

Cooper CJ et al. N Engl J Med 2014;370:13-22

META ANALYSIS OF RANDOMIZED CLINICAL TRIALS

Treatment of atherosclerotic renovascular hypertension: review of observational studies and a meta-

analysis of randomized clinical trials Paola Caielli et al. Nephrol Dial Transplant (2014) 0:1-13

NUMBER OF ANTIHYPERTENSIVE DRUGS

Treatment of atherosclerotic renovascular hypertension: review of observational studies and a meta-

analysis of randomized clinical trials Paola Caielli et al. Nephrol Dial Transplant (2014) 0:1-13

SYSTOLIC BLOOD PRESSURE RESPONSE

META ANALYSIS OF RANDOMIZED CLINICAL TRIALS

Treatment of atherosclerotic renovascular hypertension: review of observational studies and a meta-

analysis of randomized clinical trials Paola Caielli et al. Nephrol Dial Transplant (2014) 0:1-13

DIASTOLIC BLOOD PRESSURE RESPONSE

META ANALYSIS OF RANDOMIZED CLINICAL TRIALS

Hypertension Preservation of renal function

Congestive heart failure

Class IIa, LOE B Class IIa, LOE B Class I, LOE B

Percutaneous revascularization is reasonable for patients with hemodynamically significant RAS, accelerated HTN, resistant HTN, and malignant HTN

Percutaneous revacularization is reasonable for patients with RAS and progressive chronic kidney disease with bilateral RAS or a stenosis to a solitary functioning kidney

Percutaneous revascularization is indicated in patients with hemodynamically significant RAS (ie,>70% stenosis on angiography) and recurrent, unexplained pulmonary edema

ACC/AHA Guidelines on Indications for

Renal Artery Stenting ACC/AHA GUIDELINES ON INDICATIONS FOR RAS

Hirsch AT, Haskal ZJ, Hertzer NR et al. ACC/AHA 2005 guidelines for the management of patients

with peripheral arterial. J Am Coll Cardiol 2006; 47: 1239–1312

CLINICAL FACTORS FAVORING MEDICAL THERAPY OR REVASCULARIZATION OF RAS

Controlled blood pressure with stable renal function

Advanced age or limited life expectancy

Extensive comorbidities that make revascularization risky

High risk for atheroembolic complications

Concomitant renal parenchymal disease

MEDICAL THERAPY AND SURVEILLANCE

Progressive decline in glomerular filtration rate (GFR)

during treament of hypertension

Failure to achieve adequate blood pressure (BP) control

with optimal medical therapy

Rapid or recurrent decline in GFR in association with BP reduction

Decline in GFR with treatment with angiotensin converting enzyme inhibitors

or angiotensine receptor blockers

Recurrent congestive heart failure in patients with

adequate left ventricular function

REVASCULARIZATION + OPTIMAL MEDICAL THERAPY

CLINICAL FACTORS FAVORING MEDICAL THERAPY OR REVASCULARIZATION OF RAS

TAKE HOME MESSAGE

• Many patients with renovascular occlusive disease can achieve adequate BP control with stable renal function for several years.

• Clinician need to identify subsets of patients who fail medical therapy and/or progress to develop high-risk clinical phenotypes

• Renal artery stenting should be reserved for those who fail medical therapy with hypertension and clinical events