ARTS I

1
ARTS I II

• Keith D Dawkins
• Southampton University Hospital

2
Trials of PTCA (POBA v CABG)

• RITA Randomized intervention treatment of angina
  trial
• ERACI Argentine randomized trial of percutanous
  transluminal coronary angioplasty v. coronary
  artery bypass surgery in multivessel disease
• GABI The German angioplasty bypass surgery
  investigation
• EAST The Emory angioplasty v. surgery trial
• CABRI Coronary angioplasty v. bypass
  revascularization investigation
• BARI The bypass angioplasty revascularisation
  investigation
• MASS Medicine, angioplasty, or surgery trial
• GOY PTCA v. LIMA for isolated proximal LAD
  disease

1993 -1997
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Trials of PTCA (POBA v. CABG) Summary of Results

• PTCA successful in 90 of patients
• Emergency CABG required in 5-10 of PTCA patients
• Early mortality in CABG PTCA groups similar
  (1-5)
• Q-wave infarction higher in CABG pts
• Prevalence of AP at 6 months, 32 PTCA group v.
  11 CABG group
• Within 2 years 30 PTCA patients 10 CABG pts
  had reached a major cardiac endpoint (redo, AMI,
  death)
• Survival (PTCA v. CABG) similar at 8 years
• Diabetics have better survival after CABG

4
ARTS I
5
ARTS I

• Primary Objective
• The primary objective of ARTS I was to compare
  intra-coronary stenting to bypass surgery in
  patients with multivessel disease
• Effectiveness was measured in terms of Major
  Cardiac and Cerebrovascular Events (MACCE) free
  survival at one year

6
ARTS I Patient Flow
CABG
STENT
600 INTENTION TO TREAT INTENTION TO TREAT 605
1 Medical Treatment only Medical Treatment only 3
6 Crossover 3 consent withdrawal 2 LM disease 1 inappropriate selection Cross-over 8 consent withdrawal 8 exclusion criteria 1 miscommunication 1 QMI on waiting list 1 UAP on waiting list 19
13 3 urgent CABG 10 elective CABG within hosp stay 2 PTCA within hosp stay 2
580 (97) Successful treatment according to randomisation Successful treatment according to randomisation 581 (96)
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ARTS IMACCE (30 day follow-up)
CABG (605) CABG (605) Stent (600) Stent (600)
Death 83 1.8 9 1.5
CVA 71 1.3 5 0.8
AMI (Q) 134 2.8 151 2.7
Re-CABG 2 0.3 12 2.0
Re-PTCA 3 0.5 10 1.7
Total 41 6.8 52 8.7
Events prior to assigned treatment
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ARTS Trial (CABG v. PCI) Three year follow-up
100 80 60 40 20 0
PCI CABG
99.5 98.5
97.5 97.2
97.2 96.4
96.3 95.5
Event Free Survival ()
p0.08 Log Rank p0.09 Fisher
Death
0 150 300 450 600 750 900 1050
1200
Days since randomization
9
ARTS Trial (CABG v. PCI) Three year Follow-up
100 80 60 40 20 0
CABG PCI
97.0 96.8
95.2 93.8
95.0 93.3
94.7 92.7
Event Free Survival ()
p0.87 Log Rank p0.83 Fisher
AMI
0 150 300 450 600 750 900 1050
1200
Days since randomization
10
ARTS Trial (CABG v. PCI) Three year Follow-up
100 80 60 40 20 0
CABG PCI
Event Free Survival ()
96.0 95.5
91.2 90.3
89.8 89.2
88.8 87.0
p0.58 Log Rank p0.62 Fisher
Death AMI CVA
0 150 300 450 600 750 900 1050
1200
Days since randomization
11
ARTS Trial (CABG v. PCI) Three year Follow-up
100 90 80 70 60 50
95.7
87.8
85.0
83.6
91.8
CABG
Event Free Survival ()
73.5
69.5
65.7
PCI
p0.005 Log Rank p0.006 Fisher
Death AMI CVA CABG Re-PCI
0 150 300 450 600 750 900 1050
1200
Days since randomization
12
ARTS Trial (CABG v. PCI) Three year Follow-up
(Diabetic subgroup)
100 90 80 70 60 50
CABG
92.7
Death, AMI, CVA PCI CABG
Event Free Survival ()
61.6
PCI
p0.0001 Log Rank plt0.0001 Fisher
CABG Re-PCI
0 150 300 450 600 750 900 1050
1200
Days since randomization
13
Instent Restenosis
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ARTS II
15
Sirolimus Coating Modulates neointima in 30-Day
Porcine Coronary Model
Control
Sirolimus
16
Sirolimus-1X-Coated Bx VELOCITY Stent Phase 1
Study, Sao Paulo, Brazil Patient 11 LAD Lesion
PRE
POST
4-MONTH FU
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Sirolimus-Coated Bx VELOCITY Stents
With Sirolimus Coating
Stent Platform
18
ARTS II

• Study Design
• Multicentre non-randomised, open, stratified
  trial in which a total of 600 eligible patients
  will be enrolled in 45-50 centres. Patients will
  be followed-up for five years
• ARTS II is a non-randomised trial using ARTS I as
  an historical control

19
ARTS II

• Primary Objective
• To compare the effectiveness of coronary stent
  implantation using the Sirolimus drug eluting Bx
  Velocity stent with that of surgery as observed
  in ARTS I
• Effectiveness will be measured in terms of Major
  Cardiac and Cerebrovascular Events (MACCE) free
  survival at 30 days and six months

20
ARTS II

• Secondary Objectives
• To compare the three groups with respect to
• MACCE at 30 days, 6 months, 1, 3 5 years
• Cost and cost effectiveness at 30 days, 6 months,
  1, 3 5 years follow-up
• Quality of life at 30 days, 6 months, 1, 3 5
  years follow-up
• The combined endpoint of death, myocardial
  infarction and stroke, and the itemised outcomes
  death, myocardial infarction, revascularisation
  procedure and stroke
• Resource use at 30 days and 1 year

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ARTS II

• Pseudo Randomization
• Patients are stratified by clinical site in
  order to include one third of patients with three
  vessel disease and two thirds of patients with
  two-vessel disease (i.e. 2.7 lesions per patient
  overall)

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23
Sirolimus-Coated Bx Stent (UK Costs)
1,500
975
Discount
350
November 2001
24
Arts I Protocol 2.7 stents per
patient costs 4,050 for Cypher Stents
List price
25
ARTS III?
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ARTS III?

• Multicentre, randomised controlled trial
• Full range of anatomical subsets (left main,
  ostial, bifurcation, long lesions, small vessels,
  chronic total occlusion etc
• Off pump techniques, minimally invasive surgery,
  robotic surgery, arterial conduits etc
• Complete revascularisation, both PCI CABG

27
CABG (isolated) Percutaneous Coronary
Interventions (UK)
procedures
2000
1977
Society of Cardiothoracic Surgeons of Great
Britain British Cardiovascular Intervention
Society
28


http//www.sts.org
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CABG Percutaneous Coronary Interventions
(Europe)
procedures/million population
1991
1998
Cor Europaeum 20008128-138
30
Wither surgical revascularisation?
?