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

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

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?

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

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

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

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

Left Main DES: Restenosis

DES Stent Thrombosis ~1-2%

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

CABGPCI OR

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

CABG has not been standing still…

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

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

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

Circ 2005;111: 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.

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 ?

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

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

PCI (104 Sites) CABG (103 Sites) 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 Total Total Run-in Phase Data: Overall Results

Run-In Phase: Left Main Data PCI:CABG ratio for LM+3VD is 1: MeanIsolated +1VD VD+3VD Total Total PCI (104 Sites) CABG (103 Sites) Mean # of Patients/Site

Run-In Phase: Left Main Data Similar rates & types of LM procedures were performed in Europe & North America. PCI: Total LM CABG: Total LM MeanIsolated +1VD North America VD+3VD PCI: Total LM CABG: Total LM MeanIsolated +1VD Europe VD+3VD Mean # of Patients/Site

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

Left Main Disease Procedures CABGPCI PCI:CABG Ratio Europe :3 Belgium :7 France :2 Germany :3 Netherlands :1 UK :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

Left Main PCI Procedures Total LMUnprotected % Unprotected Europe Belgium France Germany Netherlands UK Average number of LM patients with PCI per site The majority of LM PCI procedures in The Netherlands are unprotected.

Left Main PCI Procedures TotalIsolated+1VD+2VD+3VD Europe Belgium France Germany Netherlands UK 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

SynTax Enrollment Oct 14 th 2005

Randomized Data DES + Left Main None!

DES + LMS Registries Patients (n) * 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: Valgimigli M. Circ 2005;111: Chieffo. Circ 2005;111: * 19 protected LM

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

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: Valgimigli M. Circ 2005;111: Chieffo. Circ 2005;111:

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

Multivariate Predictors Valgimigli M. Circ 2005;111: Distal Left Main Disease DES Use LVEF % Parsonnet Score Reference Vessel Diameter Shock Presentation Troponin T >0.02 µg/l DES BetterBMS Better

Multivariate Predictors Distal Left Main Disease DES Use LVEF % Parsonnet Score Reference Vessel Diameter Shock Presentation Troponin T >0.02 µg/l DES BetterBMS Better Valgimigli M. Circ 2005;111:

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…