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

3. Trials of PTCA (POBA v. CABG) Summary of Results 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. 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 600 INTENTION TO TREAT605 1 Medical Treatment only 3 6 Cross–over 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 581(96%) STENT CABG

7. ARTS I MACCE (30 day follow-up) CABG(605)Stent(600)Death8+3 * 1.8%91.5% CVA 7+1 * 1.3%50.8% AMI (Q) 13+4 * 2.8%15+1 * 2.7% Re-CABG20.3%122.0% Re-PTCA30.5%101.7% Total416.8%528.7% * Events prior to assigned treatment

8. 0 150 300 450 600 750 900 1050 1200 100 80 60 40 20 0 Event Free Survival (%) Days since randomization ARTS Trial (CABG v. PCI) Three year follow-up ARTS Trial (CABG v. PCI) Three year follow-up 99.5% 98.5% 97.5% 97.2% 96.4% 96.3% 95.5% PCI CABG p=0.08 Log Rank p=0.09 Fisher Death

9. 0 150 300 450 600 750 900 1050 1200 100 80 60 40 20 0 Event Free Survival (%) Days since randomization ARTS Trial (CABG v. PCI) Three year Follow-up ARTS Trial (CABG v. PCI) Three year Follow-up 97.0% 96.8% 95.2% 93.8% 95.0% 93.3% 94.7% 92.7% CABG PCI p=0.87 Log Rank p=0.83 Fisher AMI

10. 0 150 300 450 600 750 900 1050 1200 100 80 60 40 20 0 Event Free Survival (%) Days since randomization ARTS Trial (CABG v. PCI) Three year Follow-up ARTS Trial (CABG v. PCI) Three year Follow-up 96.0% 95.5% 91.2% 90.3% 89.8% 89.2% 88.8% 87.0% CABG PCI p=0.58 Log Rank p=0.62 Fisher Death AMI CVA

11. 0 150 300 450 600 750 900 1050 1200 100 90 80 70 60 50 Event Free Survival (%) Days since randomization ARTS Trial (CABG v. PCI) Three year Follow-up ARTS Trial (CABG v. PCI) Three year Follow-up 91.8% 87.8% 85.0% 83.6% CABG p=0.005 Log Rank p=0.006 Fisher Death AMI CVA CABG Re-PCI PCI 73.5% 69.5% 65.7% 95.7%

12. 0 150 300 450 600 750 900 1050 1200 100 90 80 70 60 50 Event Free Survival (%) 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 Rank p<0.0001 Fisher CABG Re-PCI PCI 61.6% Death, AMI, CVA PCI = CABG

13. Instent Restenosis

14. ARTS II

15. Sirolimus Coating Modulates neointima in 30-Day Porcine Coronary Model 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 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. £975 £1,500 Sirolimus-Coated Bx Stent (UK Costs) Discount £350 November 2001

24. Arts I Protocol ~ 2.7 stents per patient costs £4,050 for Cypher Stents * Arts I Protocol ~ 2.7 stents per patient costs £4,050 for Cypher Stents * * List price

25. ARTS III?

26. 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) Society of Cardiothoracic Surgeons of Great Britain British Cardiovascular Intervention Society procedures 1977 2000

28. http://www.sts.org

29. CABG & Percutaneous Coronary Interventions (Europe) Cor Europaeum 2000;8:128-138 procedures/million population 19911998

30. Wither surgical revascularisation? ?