ARTS I & II
Keith D Dawkins
Southampton University Hospital
Trials of PTCA (POBA v CABG)
RITA
ERACI
GABI
EAST
CABRI
BARI
Randomized intervention treatment of angina
trial
Argentine randomized trial of percutanous
transluminal coronary angioplasty v. coronary
artery bypass surgery in multivessel disease
The German angioplasty bypass surgery
investigation
The Emory angioplasty v. surgery trial
Coronary angioplasty v. bypass
revascularization investigation
The bypass angioplasty revascularisation
investigation
MASS
Medicine, angioplasty, or surgery trial
GOY
PTCA v. LIMA for isolated proximal LAD disease
1993 -1997
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
ARTS I
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
ARTS I – Patient Flow
CABG
STENT
600
1
6
13
580
(97%)
INTENTION TO TREAT
Medical Treatment
only
Medical Treatment
only
Cross–over
Cross-over
3 consent withdrawal
2 LM disease
1 inappropriate
selection
8
8
1
1
1
consent withdrawal
exclusion criteria
miscommunication
QMI on waiting list
UAP on waiting list
3 urgent CABG
10 elective CABG
within hosp stay
2 PTCA
within hosp stay
Successful treatment according to
randomisation
605
3
19
2
581
(96%)
ARTS I
MACCE (30 day follow-up)
CABG
(605)
Death
CVA
AMI (Q)
Re-CABG
Re-PTCA
Total
8+3*
7+1 *
13+4*
2
3
41
Stent
(600)
1.8%
9
1.3%
5
2.8% 15+1*
0.3%
12
0.5%
10
6.8%
52
*
1.5%
0.8%
2.7%
2.0%
1.7%
8.7%
Events prior to assigned treatment
Event Free Survival (%)
ARTS Trial (CABG v. PCI)
Three year follow-up
100
80
99.5%
98.5%
97.5%
97.2%
97.2%
96.4%
96.3%
95.5%
PCI
CABG
60
40
20
0
0
p=0.08 Log Rank
p=0.09 Fisher
Death
150
300
450
600
750
900
Days since randomization
1050
1200
Event Free Survival (%)
ARTS Trial (CABG v. PCI)
Three year Follow-up
100
80
97.0%
96.8%
95.2%
93.8%
95.0%
93.3%
94.7%
92.7%
CABG
PCI
60
40
20
0
0
p=0.87 Log Rank
p=0.83 Fisher
AMI
150
300
450
600
750
900
Days since randomization
1050
1200
Event Free Survival (%)
ARTS Trial (CABG v. PCI)
Three year Follow-up
100
CABG
PCI
80
60
40
96.0%
95.5%
91.2%
90.3%
89.8%
89.2%
88.8%
87.0%
20
0
0
p=0.58 Log Rank
p=0.62 Fisher
Death AMI CVA
150
300
450
600
750
900
Days since randomization
1050
1200
Event Free Survival (%)
ARTS Trial (CABG v. PCI)
Three year Follow-up
100
95.7%
87.8%
90
80
CABG
73.5%
69.5%
65.7%
PCI
Death AMI CVA CABG Re-PCI
50
0
83.6%
91.8%
70
60
85.0%
150
300
450
600
750
p=0.005 Log Rank
p=0.006 Fisher
900
Days since randomization
1050
1200
Event Free Survival (%)
ARTS Trial (CABG v. PCI)
Three year Follow-up (Diabetic subgroup)
100
CABG
92.7%
90
80
Death, AMI, CVA
PCI = CABG
70
61.6%
60
50
0
p=0.0001 Log Rank
p<0.0001 Fisher
CABG Re-PCI
150
300
450
600
750
900
Days since randomization
1050
PCI
1200
Instent Restenosis
ARTS II
Sirolimus Coating Modulates neointima
in 30-Day Porcine Coronary Model
Control
+ Sirolimus
Sirolimus-1X-Coated Bx VELOCITY™ Stent
Phase 1 Study, Sao Paulo, Brazil
Patient #11 LAD Lesion
PRE
POST
4-MONTH FU
Sirolimus-Coated Bx VELOCITY Stents
Stent Platform
With Sirolimus Coating
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
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
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
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)
£
£ £
Sirolimus-Coated Bx Stent (UK Costs)
£1,750
£1,500
£1,500
£1,250
£1,000
£975
£750
Discount
£500
£250
£350
£0
Plain
Drug Eluting
November 2001
Arts I Protocol ~ 2.7 stents per patient
costs
£4,050 for Cypher Stents*
*
List price
ARTS III?
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
CABG (isolated) & Percutaneous Coronary
Interventions (UK)
35000
procedures
30000
CABG
PCI
25000
20000
15000
10000
5000
0
1977
2000
Society of Cardiothoracic Surgeons of Great Britain
British Cardiovascular Intervention Society
http://www.sts.org
CABG & Percutaneous Coronary
Interventions (Europe)
800
procedures/million population
700
600
CABG
PCI
500
400
300
200
100
0
1991
1998
Cor Europaeum 2000;8:128-138
Wither surgical revascularisation?
?