FAUT-IL ENCORE RECHERCHER UNE STENOSE ARTERIELLE RENALE ?

Docteur Guillaume BOBRIE

Service d’HTA - HEGP - Paris

ANGIOPLASTY FOR LOWERING BP

Mean [95% CI] p

SBP, mmHg -6.3 [-11.7, -0.8] 0.02

DBP, mmHg -3.3 [-6.2, -0.4] 0.03

DDD -0.8 0.001

Creatinine, µM -6 [-13, 1] 0.06

Between-group differences in changes from baseline

Metaanalysis of EMMA, Scottish and DRASTIC trials N Ives et al. Nephrol Dial Transplant 2003;18:298

Limitations: near normal GFR, small trials, few stents

Van de Ven et al., Lancet 1999;353:282

STENTING TO PREVENT RESTENOSIS

Stent No stentp

No. randomized 42 42

Primary success, % 88 57<0.05

Restenosis, % 14 48<0.01

6-month patency, % 80 51 <0.05

6-month BP, mmHg 160/90 165/90 NS

6-month creatinine, µM/l 140 134 NS

Revascularisation improves renal artery patency, not upstream aortic stiffness, nor downstream parenchymal microvascular disease and fibrosis

COMPLICATIONS IN 37 PROSPECTIVE STUDIES

Death by 30 daysDeath by 30 days up to 3%up to 3%

Transient reduction in GFRTransient reduction in GFR 1-13%1-13%

Renal artery or parenchymal injuryRenal artery or parenchymal injury up to 5%up to 5%

Peri-procedural CV eventsPeri-procedural CV events up to 3%up to 3%

Distal athero-embolisationDistal athero-embolisation unknownunknown

E Balk et al. Ann Intern Med 2006;145:901

J Hiramoto et al. J Vasc Surg 2005;41:1026

346 2

74

38

92

78

45

103

59

0.1-0.2 0.2-0.5 0.5-1 >1 mm

guide wire

first balloonsecond balloon

Em

boli

rele

ased

EMBOLIC PROTECTION / ABCIXIMAB FOR STENTING

100 patients with HTN, low GFR, heart failure or angina and RAS >50%, factorial design

Protection device + abciximab

n=25

No protectiondevice + abciximab

n=25

No protectiondevice, no abciximab

n=28

Protection device, no abciximab

n=22

Ab

cix

ima

b (

Re

op

ro)

bo

lus

+ in

fusi

on

/12

h

Filter-based embolic protection device

CJ Cooper et al. Circulation 2008;117:2752

GFR at baseline and 1 month

No difference in procedural or bleeding complications

RANDOMIZED TRIALS WITH LONG-TERM FU

STAR1 STent placement in Atherosclerotic ostial RAS

Indication: controllable HTN and GFR 15-802n=140, 2-year FU, renal events

ASTRAL2 Angioplasty + STent for Renal Artery Lesions

Indication: uncertain whether to revascularise

2n=1000, 5-year FU, reciprocal creatinine plot

CORAL3 Cardiovascular Outcomes in RA LesionsIndication: SBP >155, >2 drugs, RAS >60%2n=1080, 5-year FU, CV and renal events

1 Utrecht University & Dutch Kidney Foundation2 MRC and University of Birmingham CTU3 NHLBI, Cooper CJ et al, Am Heart J 2006;152:59

STAR

Medical Revasc.No 76 64

BP, mmHg 163/82 160/83

Rx score 2.9 2.8

eGFR, ml/min 46±16 45±15

Bilateral stenosis, % 46 50

Primary endpoint,* % 22 16ns

BP at FU 155/79 151/77ns

eGFR at FU 46±20 50±22ns

All cause mortality, % 8 8ns

* >20% decrease in eGFR

L Bax et al. Ann Intern Med 2009;150:840

3 lethalcomplications

Primary end point Primary end pointplus death

Cum

ulat

ive

surv

ival

Caution: limited power, included patients falsely identified as having RAS >50% by noninvasive imaging

STAR

ASTRAL

Results from patients who completed one year of follow-upPhilip Kalra, ACC Chicago, March/April 2008

Medical Revasc

N 403 403

eGFR, ml/min 46±16 45±15

BP, mmHg 163/82 160/83

Rx score 2.8 2.8

Bilateral stenosis, % 40 40

‘Serious procedural complications’ 3%

No between group differences in Scr or BP at one year FU

Early termination for futility

ASTRAL: time to first CV event and death

Death from any cause

Time to first of MI, stroke vascular death, CHF

Philip Kalra, ACC Chicago, March/April 2008

Caution: mild to moderate stenoses

Scottish, DRASTIC, Van de Ven, STAR: stenosis >50%

ASTRAL: stenosis ‘suitable for angioplasty and stenting’

EMMA: stenosis >75% or >60% + positive lateralization test

Test for functional RAS

minimal grade

ACEI-induced GFR (n=48)1

bilat >> 50%

May result in occlusion over 33 mo (n=170)2

60%

Renal vein renin st/ivc >2 (n=49)3

80%

Pd/Pa gradient >0.90 (n=47)4

65%

1 van de Ven, Kidney Int 1998;53:986. 2 Caps, Circulation 1998;98:28663 Simon, Am J Hypertens 2000;13:1189. 4 Drieghe, Eur Heart J 2008;29:517

Benefit diluted by inclusion of non-critical stenoses?

ASTRAL: pre-specified subgroup analyses

Subgroup Groups

SCr <150, 151-249, >250 mol/l

GFR <30, 30-45, >45 ml/min

Stenosis <70%, 71-89%, >90%

Renal length <9, 9-10, >10 cm

Rapid increase in SCr

Yes, No, Not Known

No benefit at any stenosis grade

ACEI/ARB in patients with RAS

DG Hackam et al. Am Heart J 2008;156:549

Inhib. Inhib. better worse

Death, MI or stroke

1° outcome 0.70 [0.59-0.82]Death 0.56 [0.47-0.68]Stroke 0.86 [0.58-1.29]MI 1.07 [0.76-1.51]CHF 0.69 [0.53-0.90]Acute renal F* 1.87 [1.05-3.33]Hemodialysis 0.62 [0.42-0.92]

*36/60 reversible

Adjusted HR [95%CI]

3570 patients aged >65 y with renovascular disease

Incidence of primary outcome 14% per year

Consider PTRA

RAS >60%

yesResistance index > 80Kidney length < 80 mm

HTN plus high CV and renal risk

Rx including ACEIstatin, aspirin

Resistant HTN, CHF or

in Ccr

CT- or MR-angio

inCcr or kidney

size

no

yes

Full preventive Rx,6-monthly follow-up

Watchful waiting

KJ Rocha-Singh et al,Circulation 2008;118:2873

‘Grade III RAS’:reduced GFR,

refractory HTN, Congestive HF

Conclusions

• Atherosclerotic renovascular disease is a renal and CV condition associated with RAS

• Patients need CV prevention, including ACEI/ARB • Revascularisation improves renal artery patency, not

upstream aortic stiffness, nor downstream parenchymal microvascular disease

• Angioplasty ± stenting should only be considered in patients with stenosis >60% and uncontrollable or malignant HTN, acute pulmonary edema, or acute drop in GFR on ACEI/ARB

• Renovascular HTN, defined as HTN associated with RAS and cured by revascularisation, does not exist in patients with atherosclerotic RAS