FAUT-IL ENCORE RECHERCHER UNE STENOSE ARTERIELLE RENALE ?

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

2. 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 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

3. STENTING TO PREVENT RESTENOSIS Stent No stent p 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 Van de Ven et al., Lancet 1999;353:282

4. COMPLICATIONS IN 37 PROSPECTIVE STUDIES Death by 30 days up to 3% Transient reduction in GFR 1-13% Renal artery or parenchymal injury up to 5% Peri-procedural CV events up to 3% Distal athero-embolisation unknown 78 guide wire 74 first balloon 59 second balloon 45 Emboli released 38 34 10 9 J Hiramoto et al. J Vasc Surg 2005;41:1026 6 3 2 2 >1 mm 0.1-0.2 0.2-0.5 0.5-1 E Balk et al. Ann Intern Med 2006;145:901

5. EMBOLIC PROTECTION / ABCIXIMAB FOR STENTING Protection device + abciximab n=25 Protection device, no abciximab n=22 No protection device + abciximab n=25 No protection device, no abciximab n=28 100 patients with HTN, low GFR, heart failure or angina and RAS >50%, factorial design Filter-based embolic protection device Abciximab (Reopro) bolus + infusion/12 h CJ Cooper et al. Circulation 2008;117:2752

6. GFR at baseline and 1 month No difference in procedural or bleeding complications

7. RANDOMIZED TRIALS WITH LONG-TERM FU STAR1STent placement in Atherosclerotic ostialRAS Indication: controllable HTN and GFR 15-80 2n=140, 2-year FU, renal events ASTRAL2Angioplasty + STent for Renal Artery Lesions Indication: uncertain whether to revascularise 2n=1000, 5-year FU, reciprocal creatinine plot CORAL3 Cardiovascular Outcomes in RA Lesions Indication: SBP >155, >2 drugs, RAS >60% 2n=1080, 5-year FU, CV and renal events 1 Utrecht University & Dutch Kidney Foundation 2 MRC andUniversity of Birmingham CTU 3 NHLBI, Cooper CJ et al, Am Heart J 2006;152:59

8. 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 16 ns BP at FU 155/79 151/77 ns eGFR at FU 46±20 50±22 ns All cause mortality, % 8 8 ns 3 lethal complications * >20% decrease in eGFR L Bax et al. Ann Intern Med 2009;150:840

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

10. ASTRAL 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 Results from patients who completed one year of follow-up Philip Kalra, ACC Chicago, March/April 2008

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

12. 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)1bilat >> 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;98:2866 3 Simon,Am J Hypertens 2000;13:1189. 4 Drieghe, Eur Heart J 2008;29:517 Benefit diluted by inclusion of non-critical stenoses?

13. ASTRAL: pre-specified subgroup analyses No benefit at any stenosis grade

14. ACEI/ARB in patients with RAS 3570 patients aged >65 y with renovascular disease Death, MI or stroke Adjusted HR [95%CI] Inhib. Inhib. better worse 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 Incidence of primary outcome 14% per year DGHackam et al. Am Heart J 2008;156:549

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

16. 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 ± stentingshould 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