1. Left Main Stem Intervention Trials & Registries Keith D. Dawkins MD FRCP FACC Southampton University Hospital UK

2. 2 Presenter Disclosure Information The following relationships exist related to this Presentation. Advisory Board or Consultant: Abbott Boston Scientific Corporation ConorMed Eli Lilly Guidant Nycomed

3. Assessing the Left Main Data Anatomy: Ostium, Body, Bifurcation Elective vs. Emergency Surgical candidate or not? Left Ventricular Function Protected or not? Co-Morbidity: Diabetes, Renal impairment Technical Approach: Debulking, IVUS, IABP Drug Elution?

4. Why is the Left Main special? Concern over haemodynamic stability Concern in relation to the consequences of coronary dissection Unknown comparative efficacy of the available bifurcation techniques Doubt concerning long-term results

5. Balloon Angioplasty 1977 Bare metal stents 1993 Drug-Eluting stents 2002

6. Left Main Stem: Ultima Registry Events (%) Cardiac DeathQ-AMI MACE Tan WA. Circ 2001;104:1609-1614 CABG BMS 68.8%, DES 0%, POBA 15.1% N=279

7. Bare Metal Drug-Elution The contribution of DES to LMS outcomes remains uncertain!

8. Left Main DES: Restenosis

9. DES Stent Thrombosis ~1-2%

10. LMS: Medical Treatment + + Left Main Stem Medical Treatment Mortality (5 years) = 36.5% Odds Ratio (vs. CABG) = 0.32 [0.15-0.70], p=0.04 Mortality (5 years) = 36.5% Odds Ratio (vs. CABG) = 0.32 [0.15-0.70], p=0.04 Yusuf et al. Lancet 1994;344:563-570

11. CABGPCI OR

12. http://www.ctsnet.org/file/SCTS2000pages116-121LMS.pdf

13. http://www.ctsnet.org/file/SCTS2000pages116-121LMS.pdf

14. Left Main Stem: CABG Mortality Death (%) Beauford 12 mths Yeatman 24 mths French Registry 12 mths Mack 1m Off/On Pump CCAB Lu 12 mths N=3904

15. http://www.ctsnet.org/file/SCTS2000pages116-121LMS.pdf

16. CABG has not been standing still…

17. Graft Patency LIMA, SVG and Radial artery grafts Khot UN et al. Circ 2004;109:2086-2091 Occluded (%) * p=0.28p<0.0001 Radial SVGLIMA * Mean follow-up 565 ± 511 days

18. 7.6%10.1%12% per million population European Revascularisation Unger F (2004)

19. Graft Patency: On-Pump vs. Off-Pump Khan NE et al. N Engl J Med 2004;350:21-28 Patency Rate (%) * p<0.002 On-PumpOff-Pump * Mean follow-up 3 months

20. Circ 2005;111:2858-2864 Length of hospital stay, mortality rate, and long-term neurological function and cardiac outcome appear to be similar in the two groups. To definitively answer the remaining questions of whether either strategy is superior, a large-scale prospective randomized trial is required.

21. Evolution of Revascularization P C I C A B G Over the last decade, the standard of care for both CABG and PCI has continuously improved, leveling the playing field. + Off pump technique + Less invasive approach + Increased arterial revascularization + Optimal perioperative monitoring + Improved technique + Improved stent design + DES ­ High costs ­ Invasive - Restenosis - Repeat revascularization ?

22. Heart Team (surgeon & interventionalist) amenable for only one treatment approach Two Registry Arms amenable for both treatment options SynTax: All-Comers Design All patients with 3VD/LM TAXUSCABG vs Randomized Arm N=1800 (1:1) PCI all captured w/ follow up CABG 2750 captured (750 w/ follow up) Run-In Qualification Phase Site Selection

23. Run-in Phase Data : Overall Results Total # patients entered as of 12 May 2005 Run-in phase data 12072 8895 3177 Total # CABG patients Total # PCI patients

24. PCI (104 Sites) CABG (103 Sites) 86.4 30.5 60.3 22.3 26.0 8.3 Patient ratio of PCI:CABG is 1:3 Ratio of PCI:CABG for both 3VD and LM disease is 1:3 Mean # of Patients/Site Total Patients3VDLeft Main Total889562152680 Total31772317860 Run-in Phase Data: Overall Results

25. Run-In Phase: Left Main Data PCI:CABG ratio for LM+3VD is 1:10 26.0 2.6 7.1 2.7 14.5 MeanIsolated +1VD 1.8 2.31.9 1.5 8.3 +2VD+3VD Total26801852747291492 Total860274240193153 PCI (104 Sites) CABG (103 Sites) Mean # of Patients/Site

26. Run-In Phase: Left Main Data Similar rates & types of LM procedures were performed in Europe & North America. PCI: Total LM - 212 CABG: Total LM - 813 31.3 0.8 8.1 1.8 20.6 MeanIsolated +1VD North America 3.8 2.0 1.40.7 7.9 +2VD+3VD PCI: Total LM - 648 CABG: Total LM - 1867 24.2 2.1 6.7 2.9 12.4 MeanIsolated +1VD Europe 2.22.42.01.8 8.4 +2VD+3VD Mean # of Patients/Site

27. Run-In Phase: Left Main PCI Data North America (27 sites)Europe (77 sites) 8.4 7.9 5.6 1.8 Unprotected LM PCI procedures were performed 3X more often in Europe than in North America. Mean # of Patients/Site Total LMUnprotected Total648429 Total21248

28. Left Main Disease Procedures CABGPCI PCI:CABG Ratio Europe24.28.41:3 Belgium29.44.41:7 France20.29.11:2 Germany21.08.11:3 Netherlands23.718.71:1 UK32.76.91:5 Mean number of patients per site The Netherlands performs twice the number of LM PCI, while Belgium performs half, versus the rest of Europe

29. Left Main PCI Procedures Total LMUnprotected % Unprotected Europe8.45.666 Belgium4.43.068 France9.16.370 Germany8.14.455 Netherlands18.716.086 UK6.94.666 Average number of LM patients with PCI per site The majority of LM PCI procedures in The Netherlands are unprotected.

30. Left Main PCI Procedures TotalIsolated+1VD+2VD+3VD Europe8.42.22.42.01.8 Belgium4.41.02.00.80.6 France9.12.33.81.81.2 Germany8.11.91.81.72.8 Netherlands18.78.54.72.33.2 UK6.91.82.41.71.0 Average number of LM patients with PCI per site Almost half of Netherlands LM procedures are isolated LMs; approx. 1/3 of all LM in Germany are LM+3VD

31. SynTax Enrollment 445416 282 163 37 Oct 14 th 2005

32. Randomized Data DES + Left Main None!

33. DES + LMS Registries Patients (n) 10295 * 85 Debulking2.9%3.2%0% IVUS86.3%28.4%? IABP4.9%15.8%21.2% IIb/IIIa7.8%29.5%28.5% Park S-J. J Am Coll Cardiol 2005;45:351-356 Valgimigli M. Circ 2005;111:1383-1389 Chieffo. Circ 2005;111:791-795 * 19 protected LM

34. DES Registries: Bifurcation treatment Single stent Kissing stents Culotte Crush stents V stents T stents Reverse crush ± Final Kissing balloons

35. Left Main: Major Adverse Cardiac Events MACE Free (%) FU 12 monthsFU 6 months FU 17 months Park S-J. J Am Coll Cardiol 2005;45:351-356 Valgimigli M. Circ 2005;111:1383-1389 Chieffo. Circ 2005;111:791-795

36. Left Main: Death Death (%) FU 12 monthsFU 6 months FU 17 months Park S-J. J Am Coll Cardiol 2005;45:351-356 Valgimigli M. Circ 2005;111:1383-1389 Chieffo. Circ 2005;111:791-795

37. Multivariate Predictors Valgimigli M. Circ 2005;111:1383-1389 Distal Left Main Disease DES Use LVEF % Parsonnet Score Reference Vessel Diameter Shock Presentation Troponin T >0.02 µg/l 6 5 4 3 2 1 0 1 2 3 4 DES BetterBMS Better

38. Multivariate Predictors Distal Left Main Disease DES Use LVEF % Parsonnet Score Reference Vessel Diameter Shock Presentation Troponin T >0.02 µg/l 6 5 4 3 2 1 0 1 2 3 4 DES BetterBMS Better Valgimigli M. Circ 2005;111:1383-1389

39. Conclusions Randomized trials (DES vs. CABG) are required. They are unlikely to be powered for lesion sub-sets because of variations in PCI approach. In planning Left Main PCI, consider individual patient and lesion specific risk factors. Plan the strategy…