ARTS I & II

1. ARTS I & II Keith D Dawkins Southampton University Hospital

2. Trials of PTCA (POBA v CABG) RITA Randomized intervention treatment of angina trial ERACIArgentine randomized trial of percutanous transluminal coronary angioplasty v. coronary artery bypass surgery in multivessel disease GABIThe German angioplasty bypass surgery investigation EAST The Emory angioplasty v. surgery trial CABRI Coronary angioplasty v. bypass revascularization investigation BARIThe bypass angioplasty revascularisation investigation MASS Medicine, angioplasty, or surgery trial GOY PTCA v. LIMA for isolated proximal LAD disease 1993 -1997

3. 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

7. ARTS IMACCE (30 day follow-up) *Events prior to assigned treatment

8. 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 (%) p=0.08 Log Rank p=0.09 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 (%) p=0.87 Log Rank p=0.83 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% p=0.58 Log Rank p=0.62 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% CABG 91.8% Event Free Survival (%) 73.5% 69.5% 65.7% PCI p=0.005 Log Rank p=0.006 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 p=0.0001 Log Rank p<0.0001 Fisher CABG Re-PCI 0 150 300 450 600 750 900 1050 1200 Days since randomization

13. Instent Restenosis

14. 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

17. 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

21. 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)

22. £ £ £

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?

26. 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

29. CABG & Percutaneous Coronary Interventions (Europe) procedures/million population 1991 1998 Cor Europaeum 2000;8:128-138

30. Wither surgical revascularisation? ?