Left Main Intervention: Where are we in 2015? David A. Cox, MD FSCAI Director, Cardiology Research Associate Director, Cardiac Cath Lab Lehigh Valley Health Network Allentown, PA Fall Fellows Course Laa Las Vegas 2015
Disclosures Advisory Board: Abbott Vascular Boston Scientific Medtronic, Inc. themedicinescompany
PCI vs CABG
PCI for LM PCI of LM attractive: Large diameter vessel Proximal location BUT.. Lots of LM disease involves the bifurcation (high risk of restenosis) Many patients have multivessel CAD: potential survival benefit with CABG
MACCE to 5 Years Left Main Subset N=705 CABG (N=348) TAXUS (N=357) Cumulative Event Rate (%) 50 25 0 Before 1 year * 13.7% vs 15.8% P=0.44 1-2 years * 7.5% vs 10.3% P=0.22 2-3 years * 5.2% vs 5.7% P=0.78 P=0.12 3-4 years * 6.4% vs 8.3% P=0.35 4-5 years * 5.9% vs 5.5% P=0.82 36.9% 31.0% 0 12 24 36 48 60 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE log-rank P value; * Binary rates SYNTAX 3VD 5-year Outcomes TCT 2012 Serruys 23 October 2012 Slide 7 Serruys PW et al. Lancet 2013;381:629 38
Left Main Disease 5-year Outcomes (N=705) CABG (n=348) TAXUS (n=357) P=0.53 P=0.10 P=0.03 P<0.001 P=0.12 Patients (%) 31.0 36.9 All Death MI CVA Revasc. MACCE SYNTAX 3VD 5-year Outcomes TCT 2012 Mohr 23 October 2012 Slide 8 Mohr FW et al. Lancet 2013;381:629 38
MACCE to 5 Years by SYNTAX Score Tercile LM Subset High Scores 33 CABG (N=149) TAXUS (N=135) CABG PCI P value 50 P=0.003 LM Disease 46.5% Death 14.1% 20.9% 0.11 CVA 4.9% 1.6% 0.13 MACCE (%) 25 29.7% MI 6.1% 11.7% 0.13 Death, CVA or MI 22.1% 26.1% 0.40 0 0 12 24 Months 36 48 60 Revasc. 11.6% 34.1% <0.001 SYNTAX 3VD 5-year Outcomes TCT 2012 Serruys 23 October 2012 Slide 9 Serruys PW et al. Lancet 2013;381:629 38
MACCE to 5 Years by SYNTAX Score Tercile LM Subset Low to Intermediate Scores (0-32) CABG (N=196) TAXUS (N=221) CABG PCI P value Cumulative Event Rate (%) 50 25 P=0.74 LM Disease 32.1% 31.3% Death 15.1% 7.9% 0.02 CVA 3.9% 1.4% 0.11 MI 3.8% 6.1% 0.33 Death, CVA or MI 19.8% 14.8% 0.16 0 0 12 24 36 48 60 Months Since Allocation Revasc. 18.6% 22.6% 0.36 SYNTAX 3VD 5-year Outcomes TCT 2012 Serruys 23 October 2012 Slide 10 Serruys PW et al. Lancet 2013;381:629 38
Bottom Line Benefit with CABG over PCI is limited to fewer repeat revascularizations, at a cost of more strokes High SYNTAX score patients (>33) benefit from CABG
CABG vs. EES in New York Registry 18,480 propensity-score matched CAD pts (median f/u 2.9 y) PCI associated with less 30-day death, stroke CABG assc. w/ less long-term MI, revasc. CABG = PCI for long-term death Bangalore S et al. N Engl J Med 2015;372:1213-1222.
I d rather die than have a stroke What kind of stroke will I have? A mini-stroke or a Big One???
CVA: not taken lightly
Most patients would rather have repeat PCI than a CVA!!!!
ACC/AHA/SCAI Gdls for Revascularization of Left Main Disease: Pre-2009 I IIa IIb III Post-2009 I IIa IIb III CABG PCI CABG PCI Kushner et. Al. JACC Vol 54. No 23, 2009
ACC/AHA/SCAI Guidelines IIa IIb LMCA PCI is reasonable in pts with class III angina and >50% LM stenosis who are not eligible for CABG Stenting of the LMCA as an alternative to CABG may be considered in pts with anatomic conditions that are associated with a low risk of PCI procedural complications and clinical conditions that predict an increased risk of adverse surgical outcomes ACC/AHA/SCAI 2009 Focused Updates for STEMI and PCI. Circulation 2009;120:2271 2306
ACC/AHA/SCAI GDLS 2009 focused update of PCI GDL Class IIb, LoE B recommendation the best case for PCI as an alternative to CABG for LM CAD is in ostial and midbody lesions without additional multivessel disease Routine angiographic follow-up after LM PCI omitted from guidelines
PCI vs CABG for Left Main Is PCI really non-inferior or superior to CABG in Syntax Score <33 pts with LM ds. for the events that really matter (death, stroke, or MI)? Can PCI outcomes be improved by..? Use of better DES? (e.g. XIENCE V) Use of better pharmacotherapy (e.g. bivalirudin) IVUS/FFR? (used in <10% in SYNTAX) More frequent staging? (14% in SYNTAX) Avoidance of routine angiographic FU*? Can CABG outcomes be further improved? *Currently not recommended by the ACC/AHA Guidelines. Circulation 2009;120:2271 2306
EXCEL: Study Design 3600 pts with unprotected left main disease SYNTAX score 32 Consensus agreement by heart team Yes (N=2600) R @ 165 international sites No (N=1000) Enrollment registry PCI (Xience Prime) (N=1300) CABG (N=1300) Clinical follow-up: 1 mo, 6 mo and yearly through 5 years
What is Novel About EXCEL? The primary endpoint: Death, MI or stroke at 3 years Revascularization not pri edp
MACCE to 5 Years by SYNTAX Score Tercile LM Subset Low to Intermediate Scores (0-32) CABG (N=196) TAXUS (N=221) CABG PCI P value Cumulative Event Rate (%) 50 25 P=0.74 LM Disease 32.1% 31.3% Death 15.1% 7.9% 0.02 CVA 3.9% 1.4% 0.11 MI 3.8% 6.1% 0.33 Death, CVA or MI 19.8% 14.8% 0.16 0 0 12 24 36 48 60 Months Since Allocation Revasc. 18.6% 22.6% 0.36 SYNTAX 3VD 5-year Outcomes TCT 2012 Serruys 23 October 2012 Slide 22 Serruys PW et al. Lancet 2013;381:629 38
What is Novel About EXCEL? Restriction of enrollment to Syntax Score 32
What is Novel About EXCEL? Use of 2 nd Generation DES
What is Novel About EXCEL? Optimal PCI and CABG Technique
EXCEL Evaluation of Xience Prime versus CABG for Effectiveness of Left Main Revascularization Inclusion Criteria Significant LM disease by heart team consensus - Angiographic DS 70%, or - Angiographic DS 50% to <70% with - a markedly positive noninvasive study, and/or - IVUS MLA <6.0 mm 2, and/or - FFR <0.80
EXCEL: PCI Procedure Highlights DAPT and statin pre-loading: Required IVUS: Strongly recommended to guide LM PCI FFR: Strongly recommended to assess borderline lesions
EXCEL: PCI Procedure Highlights Distal LM bifurcation: Provisional stenting recommended Hemodynamic support: Permitted, not usually required Staging: Liberal use permitted (<2 weeks preferred) Routine FU angiography: Not permitted
EXCEL: Status Given financial considerations, the sponsor has decided to cap enrollment at 1900 pts; the sponsor and PIs remain blinded With 2600 pts randomized, the trial had 90% power to demonstrated noninferiority between PCI and CABG for the primary endpoint of death/cva/mi at median FU 3 years With 1900 pts randomized, the trial has 80% power for the primary endpoint All 1900 pts have been randomized
NOBLE: Study Design 1200 pts with unprotected left main disease With 3 additional non-complex lesions (excludes length >25 mm, CTO, 2-stent bifurcation, calcified or tortuous vessels) R @ 26 EU sites PCI (Biomatrix BES) (N=600) CABG (N=600) Clinical follow-up: Through 5 years
NOBLE: Status All 1200 pts have been randomized c/o Evald Høj Christiansen
Temporal Trends (n=2,360), 2015 Outcomes of LM Revascularization Park SJ, Ahn JM et al, Circ Cardiovasc Interv. 2015;8:e001846.
New Data from ASAN MAIN registry, 2014 Adjusted Hazard Ratios of MACCE Between CABG and PCI for LM Disease (N=2360) Outcomes of PCI Are Getting Better Over time! Mainly due to more P for Interaction IVUS/FFR = 0.002and Better DES. BMS (1995-2002) Early DES (2003-2006) Late DES (2007-2010) HR (95% CI) P value 0.33 (0.23-0.47) <0.001 0.53 (0.35-0.80) 0.005 1.01 (0.68-1.49) 0.32 0.1 1 10 PCI better CABG better
Park SJ, Ahn JM et al, Circ Cardiovasc Interv. 2015;8:e001846. Adjusted Hazard Ratios of MACCE Between CABG and PCI Death Death, MI or Stroke Repeat Revascularization P for Interaction = 0.011 P for Interaction = 0.017 P for Interaction = 0.20 HR (95% CI) P value HR (95% CI) P value HR (95% CI) P value BMS 1.36 (0.52-3.52) 0.53 Early DES 0.66 (0.32-1.37) 0.27 Late DES 0.31 (0.13-0.71) 0.015 1.49 (0.67-3.31) 0.33 0.80 (0.43-1.50) 0.49 0.44 (0.23-0.85) 0.015 6.88 (3.21-14.7) <0.001 5.26 (2.73-10.1) <0.001 5.07 (2.12-12.1) <0.001 0.1 1 10 0.1 1 10 0.1 1 10 100 PCI better CABG better PCI better CABG better PCI better CABG better
FAME3 Patients with Angiographically 3 Vessel Disease without LM R FFR Guided PCI + OMT CABG Primary Endpoint at 2 years: Death + MI + Repeat R + Stroke PI ; William Fearon,MD
Distal LM Stent Technique Less 2 stent approach P=0.14 100 Percent (%) 80 60 40 40.4 33.3 66.7 Two stent Single Stent cross over 20 59.6 0 Before Routine Use of FFR After Routine Use of FFR
Restenosis at 2 year Pooled Analysis in 403 Patients with LM PCI Using SES % 30 Ostial and Shaft Bifurcation PCI 25.4 25 Stent 20Crossover (provisional second stent) 15 Is Clearly Better! 6.3 10 4.5 5 0 3/67 14/222 29/114 Single Two stent Kang et al. Circ Cardiovasc Interv 2011;4:1168-74
Angiographic Narrowing May Not Be Functional Narrowing! % 42% 7% (DS>50%) (FFR<0.80) Kang SJ, Catheterization and Cardiovascular Interventions. 2014;83(4):545-52.
If You Want To Treat LCX Ostium After Single Stent into LM/LAD Consider FFR First! Or Consider a Nordic Bifurcation approach and only stent if TIMI 2 flow. Ignore How Cx Looks
LM PCI: Key Points Heart Team approach Never ad hoc Be skilled at bifurcation stenting You may be comfortable doing LM PCI your new hospital may not Your partner s eyes and advice-- critical Double scrub if possible EXCEL and NOBLE trials
ACC/AHA/SCAI 2011 PCI GDL PCI to improve survival is reasonable in patients with acute STEMI when unprotected LM is the culprit lesion distal coronary flow is less than TIMI 3 PCI can be performed more rapidly and safely than CABG. Go for it!