ARTS I & IIARTS I & IIARTS I & IIARTS I & II

Keith D DawkinsSouthampton University Hospital

Trials of PTCA (POBA v CABG)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

Trials of PTCA (POBA v. CABG)Summary of ResultsTrials 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 IARTS IARTS IARTS I

ARTS IARTS 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 FlowARTS I – Patient Flow

600600 INTENTION TO TREAT 605605

1Medical Treatment

onlyMedical Treatment

only3

6

Cross–over3 consent withdrawal2 LM disease1 inappropriate selection

Cross-over8 consent withdrawal8 exclusion criteria1 miscommunication1 QMI on waiting list1 UAP on waiting list

19

133 urgent CABG10 elective CABGwithin hosp stay

2 PTCAwithin hosp stay 2

580580

(97%)(97%)Successful treatment according to

randomisation581581

(96%)(96%)

STENT CABG

ARTS IMACCE (30 day follow-up)ARTS IMACCE (30 day follow-up)

CABGCABG(605)(605)

StentStent(600)(600)

DeathDeath 8+3* 1.8% 9 1.5%

CVACVA 7+1 * 1.3% 5 0.8%

AMI (Q)AMI (Q) 13+4* 2.8% 15+1* 2.7%

Re-CABGRe-CABG 2 0.3% 12 2.0%

Re-PTCARe-PTCA 3 0.5% 10 1.7%

TotalTotal 41 6.8% 52 8.7%

**Events prior to assigned treatmentEvents prior to assigned treatment

0 150 300 450 600 750 900 1050 1200

100

80

60

40

20

0

Even

t Fr

ee S

urv

ival (%

)

Days since randomization

ARTS Trial (CABG v. PCI)Three year follow-upARTS Trial (CABG v. PCI)Three year follow-up

99.5%98.5%

97.5%97.2%

97.2%96.4%

96.3%95.5%

PCICABG

p=0.08 Log Rankp=0.09 FisherDeath

0 150 300 450 600 750 900 1050 1200

100

80

60

40

20

0

Even

t Fr

ee S

urv

ival (%

)

Days since randomization

ARTS Trial (CABG v. PCI)Three year Follow-upARTS Trial (CABG v. PCI)Three year Follow-up

97.0%96.8%

95.2%93.8%

95.0%93.3%

94.7%92.7%

CABGPCI

p=0.87 Log Rankp=0.83 FisherAMI

0 150 300 450 600 750 900 1050 1200

100

80

60

40

20

0

Even

t Fr

ee S

urv

ival (%

)

Days since randomization

ARTS Trial (CABG v. PCI)Three year Follow-upARTS Trial (CABG v. PCI)Three year Follow-up

96.0%95.5%

91.2%90.3%

89.8%89.2%

88.8%87.0%

CABGPCI

p=0.58 Log Rankp=0.62 Fisher

Death AMI CVA

0 150 300 450 600 750 900 1050 1200

100

90

80

70

60

50

Even

t Fr

ee S

urv

ival (%

)

Days since randomization

ARTS Trial (CABG v. PCI)Three year Follow-upARTS Trial (CABG v. PCI)Three year Follow-up

91.8%

87.8%85.0%

83.6%

CABG

p=0.005 Log Rankp=0.006 FisherDeath AMI CVA CABG Re-PCI

PCI

73.5%

69.5%65.7%

95.7%

0 150 300 450 600 750 900 1050 1200

100

90

80

70

60

50

Even

t Fr

ee S

urv

ival (%

)

Days since randomization

ARTS Trial (CABG v. PCI)Three year Follow-up (Diabetic subgroup)ARTS Trial (CABG v. PCI)Three year Follow-up (Diabetic subgroup)

92.7%

CABG

p=0.0001 Log Rankp<0.0001 FisherCABG Re-PCI

PCI

61.6%

Death, AMI, CVAPCI = CABG

Instent RestenosisInstent Restenosis

ARTS IIARTS IIARTS IIARTS II

Sirolimus Coating Modulates neointimain 30-Day Porcine Coronary ModelSirolimus Coating Modulates neointimain 30-Day Porcine Coronary Model

ControlControl + Sirolimus + Sirolimus

Sirolimus-1X-Coated Bx VELOCITY™ StentPhase 1 Study, Sao Paulo, BrazilPatient #11 LAD Lesion

Sirolimus-1X-Coated Bx VELOCITY™ StentPhase 1 Study, Sao Paulo, BrazilPatient #11 LAD Lesion

PREPREPOSTPOST

4-MONTH FU4-MONTH FU

Sirolimus-Coated Bx VELOCITY Stents Sirolimus-Coated Bx VELOCITY Stents

With Sirolimus CoatingWith Sirolimus CoatingStent PlatformStent Platform

ARTS IIARTS 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 IIARTS 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 IIARTS II

Secondary ObjectivesTo 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 IIARTS 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)

££ ££ ££

£0

£250

£500

£750

£1,000

£1,250

£1,500

£1,750

Plain Drug Eluting

£975

£1,500

Sirolimus-Coated Bx Stent (UK Costs)Sirolimus-Coated Bx Stent (UK Costs)

Discount

£350

November 2001

Arts I Protocol ~ 2.7 stents per patientcosts

£4,050 for Cypher Stents*

Arts I Protocol ~ 2.7 stents per patientcosts

£4,050 for Cypher Stents*

*List price

ARTS III?ARTS III?ARTS III?ARTS III?

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

0

5000

10000

15000

20000

25000

30000

35000

CABGPCI

CABG (isolated) & Percutaneous Coronary Interventions (UK)CABG (isolated) & Percutaneous Coronary Interventions (UK)

Society of Cardiothoracic Surgeons of Great BritainBritish Cardiovascular Intervention Society

procedures

1977 2000

http://www.sts.org

0

100

200

300

400

500

600

700

800

CABGPCI

CABG & Percutaneous Coronary Interventions (Europe)CABG & Percutaneous Coronary Interventions (Europe)

Cor Europaeum 2000;8:128-138

procedures/million population

1991 1998

Wither surgical revascularisation?Wither surgical revascularisation?

?