Philip A Kalra Lead Nephrologist for ASTRAL, Hope Hospital, Salford, UK, On behalf of the ASTRAL TMC and collaborators UK MULTI-CENTRE TRIAL IN ATHEROSCLEROTIC RENOVASCULAR DISEASE ASTRAL Angioplasty and STent for Renal Artery Lesions

ASTRAL Trial Schema Diagnosis of ARVD (Unilateral or Bilateral) Revascularisation not contraindicated Uncertain whether to revascularise Randomisation No revascularisation Medical Treatment only Revascularisation with angioplasty and/or stent (and medical treatment)

PATIENT CHARACTERISTICS BY RANDOMISED TREATMENT Revasc.MedicalP-value Mean age (range)70 (42 – 86)71 (43 – 88)0.7 Male63% 0.9 Ex-smoker52%55%0.3 Current20%22%0.5 Diabetes31%29%0.5 CHD49%48%0.2 PVD41%40%0.7 Stroke18%19%0.4 Dialysis0%0.3%0.5

LABORATORY DATA BY RANDOMISED TREATMENT Revasc.MedicalP-value SCr (μmol/l)179 (66 – 551) 178 (64 – 750) 0.9 Rapid increase in SCr12% 0.9 GFR (ml/min)40.3 (5.4 – 124.5) 39.8 (7.1 – 121.7) 0.7 Urinary Protein (g/day)0.54 (0 – 4.77) 0.72 (0 – 7.7) 0.2 Albumin:Creatinine ratio 70.2 (0 – 2740) 71.7 (0 – 2466) 0.9

LABORATORY DATA BY RANDOMISED TREATMENT Revasc.MedicalP-value Systolic BP149 (87 – 270) 152 (90 – 241) 0.07 Diastolic BP76 (45 – 120) 76 (46 – 130) 0.6 Cholesterol (mmol/l) 4.68 (0.1 – 14.8) 4.71 (1.9 – 9.6) 0.8

ANGIOGRAPHIC DATA BY RANDOMISED TREATMENT Revasc.MedicalP-value % Stenosis76% (40 – 100%)75% (20 – 100%)0.3 Renal length9.7cm (6 – 14)9.7cm (6 – 20)0.5 Location of ostial/distal ARVD lesion Left kidney24%20%0.2 Right kidney18%17% Both50%57% Missing data8%6%

CONCOMITANT MEDICINE BY RANDOMISED TREATMENT Revasc.MedicalP-value Anti-hypertensives97%99%0.2 Diuretic70%67% Ca 2 antagonist61%68% Beta-blocker46%52% ACE-I, A-II antagonist47%38% Alpha-blocker40%37% Mean no. anti-hypertensives2.8 (1 - 6) 0.9

CONCOMITANT MEDICINE BY RANDOMISED TREATMENT Revasc.MedicalP-value Anti-platelets76%78%0.5 Aspirin91%93% Cholesterol lowering80% 1.0 Statin96%95% Warfarin11% 1.0

SAFETY – IMMEDIATE POST-OP COMPLICATIONS 24 patients experienced an immediate post-op complication –Revascularisation = 23 / 308 (7%) –Medical = 1 / 18 (6%) Most patients (88%) had one complication

PLOT OF SCr OVER TIME

MEAN CHANGE IN SCr BETWEEN BASELINE AND 1 YEAR Negative change = Improvement in SCr (i.e. reduction in SCr)

MEAN CHANGE IN SCr

MEAN CHANGE IN SYSTOLIC BP

PLOT OF DIASTOLIC BP OVER TIME

TIME TO FIRST OF MI, STROKE, VASCULAR DEATH OR HOSPITALISATION FOR ANGINA, FLUID OVERLOAD OR CARDIAC FAILURE HR=0.90, 95% CI=0.66 to 1.15

MORTALITY HR=0.92, 95% CI=0.68 to 1.26

PRE-SPECIFIED SUBGROUP ANALYSES SubgroupGroups SCr≤150, , ≥250μmol/l GFR 45ml/min Stenosis≤70%, 71-89%, ≥90% Renal Length≤9, 9-10, >10cm Rapid increase in SCr Yes, No, Not Known

SUMMARY Currently no evidence of a benefit for revascularisation on renal function in the ARVD patients entered into ASTRAL – those in whom clinicians ‘uncertain’ of whether to revascularise Also no evidence of differences between the arms for any of the secondary endpoints (i.e. blood pressure, major events) No evidence of differences in treatment effect across the various subgroups Longer follow-up is needed Plan to update meta-analysis published in NDT in 2003 to include ASTRAL and other trials