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 revasculariseRandomisation

No revascularisation

Medical Treatment only

Revascularisation

with angioplasty and/or stent

(and medical treatment)

PATIENT CHARACTERISTICS BY PATIENT CHARACTERISTICS BY RANDOMISED TREATMENTRANDOMISED TREATMENT

Revasc. Medical P-value

Mean age (range) 70 (42 – 86) 71 (43 – 88) 0.7

Male 63% 63% 0.9

Ex-smoker 52% 55% 0.3

Current 20% 22% 0.5

Diabetes 31% 29% 0.5

CHD 49% 48% 0.2

PVD 41% 40% 0.7

Stroke 18% 19% 0.4

Dialysis 0% 0.3% 0.5

LABORATORY DATA BY LABORATORY DATA BY RANDOMISED TREATMENTRANDOMISED TREATMENT

Revasc. Medical P-value

SCr (μmol/l) 179

(66 – 551)

178

(64 – 750)

0.9

Rapid increase in SCr 12% 12% 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 LABORATORY DATA BY RANDOMISED TREATMENTRANDOMISED TREATMENT

Revasc. Medical P-value

Systolic BP 149

(87 – 270)

152

(90 – 241)

0.07

Diastolic BP 76

(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 ANGIOGRAPHIC DATA BY RANDOMISED TREATMENTRANDOMISED TREATMENT

Revasc. Medical P-value

% Stenosis 76% (40 – 100%) 75% (20 – 100%) 0.3

Renal length 9.7cm (6 – 14) 9.7cm (6 – 20) 0.5

Location of ostial/distal ARVD lesion

Left kidney 24% 20% 0.2

Right kidney 18% 17%

Both 50% 57%

Missing data 8% 6%

CONCOMITANT MEDICINE BY CONCOMITANT MEDICINE BY RANDOMISED TREATMENTRANDOMISED TREATMENT

Revasc. Medical P-value

Anti-hypertensives 97% 99% 0.2

Diuretic 70% 67%

Ca2 antagonist 61% 68%

Beta-blocker 46% 52%

ACE-I, A-II antagonist 47% 38%

Alpha-blocker 40% 37%

Mean no. anti-hypertensives 2.8 (1 - 6) 2.8 (1 - 6) 0.9

CONCOMITANT MEDICINE BY CONCOMITANT MEDICINE BY RANDOMISED TREATMENTRANDOMISED TREATMENT

Revasc. Medical P-value

Anti-platelets 76% 78% 0.5

Aspirin 91% 93%

Cholesterol lowering 80% 80% 1.0

Statin 96% 95%

Warfarin 11% 11% 1.0

SAFETY – IMMEDIATE POST-OP SAFETY – IMMEDIATE POST-OP COMPLICATIONSCOMPLICATIONS

• 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 TIMEPLOT OF SCr OVER TIME

MEAN CHANGE IN SCr BETWEEN MEAN CHANGE IN SCr BETWEEN BASELINE AND 1 YEARBASELINE AND 1 YEAR

0

50

100

150

< -70

-70 to

-51

-50 to

-31

-30 to

-11

-10 to

10

10 to

30

31 to

50

51 to

70

71 to

90

91 to

110

111

to 1

30

131

to 1

50>15

0

No

. of

pa

tie

nts

Revasc. Medical

Negative change = Improvement in SCr (i.e. reduction in SCr)

MEAN CHANGE IN SCrMEAN CHANGE IN SCr

MEAN CHANGE IN SYSTOLIC BPMEAN CHANGE IN SYSTOLIC BP

PLOT OF DIASTOLIC BP OVER TIMEPLOT OF DIASTOLIC BP OVER TIME

TIME TO FIRST OF MI, STROKE, VASCULAR DEATH TIME TO FIRST OF MI, STROKE, VASCULAR DEATH OR HOSPITALISATION FOR ANGINA, FLUID OR HOSPITALISATION FOR ANGINA, FLUID

OVERLOAD OR CARDIAC FAILUREOVERLOAD OR CARDIAC FAILURE

HR=0.90, 95% CI=0.66 to 1.15

MORTALITYMORTALITY

HR=0.92, 95% CI=0.68 to 1.26

PRE-SPECIFIED SUBGROUP PRE-SPECIFIED SUBGROUP ANALYSESANALYSES

Subgroup Groups

SCr ≤150, 151-249, ≥250μmol/l

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

Stenosis ≤70%, 71-89%, ≥90%

Renal Length ≤9, 9-10, >10cm

Rapid increase in SCr

Yes, No, Not Known

SUMMARYSUMMARY

• 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