FAUTIL ENCORE RECHER UNE STENOSE ARTERIELLE RENALE Docteur

FAUT-IL ENCORE RECHER UNE STENOSE ARTERIELLE RENALE ? Docteur Guillaume BOBRIE Service d’HTA - HEGP - Paris

ANGIOPLASTY FOR LOWERING BP Between-group differences in changes from baseline Mean [95% CI] p SBP, mm. Hg DBP, mm. Hg -6. 3 -3. 3 [-11. 7, -0. 8] [-6. 2, -0. 4] 0. 02 0. 03 DDD Creatinine, µM -0. 8 -6 [-13, 1] 0. 001 0. 06 Limitations: near normal GFR, small trials, few stents Metaanalysis of EMMA, Scottish and DRASTIC trials N Ives et al. Nephrol Dial Transplant 2003; 18: 298

STENTING TO PREVENT RESTENOSIS Stent No stent No. randomized 42 42 Primary success, % 88 57 <0. 05 Restenosis, % 14 48 <0. 01 6 -month patency, % 6 -month BP, mm. Hg 6 -month creatinine, µM/l 80 160/90 140 p 51 <0. 05 165/90 NS 134 NS Revascularisation improves renal artery patency, not upstream aortic stiffness, nor downstream parenchymal microvascular disease and fibrosis Van de Ven et al. , Lancet 1999; 353: 282

COMPLICATIONS IN 37 PROSPECTIVE STUDIES Death by 30 days Transient reduction in GFR Renal artery or parenchymal injury Peri-procedural CV events Distal athero-embolisation up to 3% 1 -13% up to 5% up to 3% unknown J Hiramoto et al. J Vasc Surg 2005; 41: 1026 Emboli released E Balk et al. Ann Intern Med 2006; 145: 901 74 78 guide wire first balloon second balloon 59 34 38 45 6 0. 1 -0. 2 -0. 5 9 10 0. 5 -1 2 2 3 >1 mm

EMBOLIC PROTECTION / ABCIXIMAB FOR STENTING 100 patients with HTN, low GFR, heart failure or angina and RAS >50%, factorial design Abciximab (Reopro) bolus + infusion/12 h Filter-based embolic protection device Protection device + abciximab n=25 Protection device, no abciximab n=22 No protection device + abciximab n=25 No protection device, no abciximab n=28 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 STAR 1 STent placement in Atherosclerotic ostial RAS Indication: controllable HTN and GFR 15 -80 2 n=140, 2 -year FU, renal events ASTRAL 2 Angioplasty + STent for Renal Artery Lesions Indication: uncertain whether to revascularise 2 n=1000, 5 -year FU, reciprocal creatinine plot CORAL 3 Cardiovascular Outcomes in RA Lesions Indication: SBP >155, >2 drugs, RAS >60% 2 n=1080, 5 -year FU, CV and renal events 1 Utrecht University & Dutch Kidney Foundation 2 MRC and University of Birmingham CTU 3 NHLBI, Cooper CJ et al, Am Heart J 2006; 152: 59

STAR Medical Revasc. 76 64 163/82 160/83 2. 9 2. 8 46± 16 45± 15 Bilateral stenosis, % 46 50 Primary endpoint, * % 22 16 ns BP at FU 155/79 151/77 ns e. GFR at FU 46± 20 50± 22 ns 8 8 ns No BP, mm. Hg Rx score e. GFR, ml/min All cause mortality, % * >20% decrease in e. GFR L Bax et al. Ann Intern Med 2009; 150: 840 3 lethal complications

STAR Cumulative survival Primary end point plus death Caution: limited power, included patients falsely identified as having RAS >50% by noninvasive imaging

ASTRAL Medical N 403 e. GFR, ml/min 46± 16 BP, mm. Hg 163/82 Rx score 2. 8 Bilateral stenosis, % 40 ‘Serious procedural complications’ Revasc 403 45± 15 160/83 2. 8 40 3% No between group differences in Scr or BP at one year FU Early termination for futility Results from patients who completed one year of follow-up Philip Kalra, ACC Chicago, March/April 2008

ASTRAL: time to first CV event and death Time to first of MI, stroke vascular death, CHF Philip Kalra, ACC Chicago, March/April 2008 Death from any cause

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 ACEI-induced GFR (n=48)1 minimal grade 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% van de Ven, Kidney Int 1998; 53: 986. 2 Caps, Circulation 1998; 98: 2866 3 Simon, Am J Hypertens 2000; 13: 1189. 4 Drieghe, Eur Heart J 2008; 29: 517 1 Benefit diluted by inclusion of non-critical stenoses?

ASTRAL: pre-specified subgroup analyses Subgroup Groups SCr <150, 151 -249, >250 mmol/l GFR <30, 30 -45, >45 ml/min Stenosis <70%, 71 -89%, >90% Renal length Rapid increase in SCr <9, 9 -10, >10 cm Yes, Not Known No benefit at any stenosis grade

ACEI/ARB in patients with RAS 3570 patients aged >65 y with renovascular disease Death, MI or stroke Inhib. better Inhib. worse Adjusted HR [95%CI] 1° outcome Death Stroke MI CHF Acute renal F* Hemodialysis 0. 70 [0. 59 -0. 82] 0. 56 [0. 47 -0. 68] 0. 86 [0. 58 -1. 29] 1. 07 [0. 76 -1. 51] 0. 69 [0. 53 -0. 90] 1. 87 [1. 05 -3. 33] 0. 62 [0. 42 -0. 92] *36/60 reversible Incidence of primary outcome 14% per year DG Hackam et al. Am Heart J 2008; 156: 549

HTN plus high CV and renal risk Rx including ACEI statin, aspirin ‘Grade III RAS’: reduced GFR, refractory HTN, Congestive HF Resistant HTN, CHF or in Ccr KJ Rocha-Singh et al, Circulation 2008; 118: 2873 CT- or MR-angio RAS >60% Watchful waiting no Full preventive Rx, 6 -monthly follow-up yes in Ccr or kidney size Consider PTRA yes Resistance index > 80 Kidney length < 80 mm

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