Left Main Intervention: Will it become standard of care? David Cox, MD FSCAI, FACC Director, Interventional Cardiology Research Associate Director, Cardiac Cath Lab Lehigh Valley Health Network Allentown, PA Laa Fall Fellows Course Las Vegas 2014
Disclosures Advisory Board: Abbott Vascular Boston Scientific Medtronic, Inc. themedicinescompany
Medicine Changes!!! Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults There is no evidence to support continued use of specific LDL treatment targets. Will IMPROVE-IT change GDL s again?
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 FREEDOM and SYNTAX TRIALS
SYNTAX SCORE: Risk Stratify
MACCE to 5 Years Left Main Subset N=705 TAXUS (N=357) CABG (N=348) 1-2 years* 13.7% vs 15.8% 7.5% vs 10.3% P=0.44 P=0.22 Cumulative Event Rate (%) Before 1 year* 50 2-3 years* 5.2% vs 5.7% P=0.78 3-4 years* 6.4% vs 8.3% P=0.35 36.9% P=0.12 25 0 4-5 years* 5.9% vs 5.5% P=0.82 31.0% 0 12 24 36 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE Serruys PW et al. Lancet 2013;381:629 38 log-rank P value;*binary rates SYNTAX 3VD 5-year Outcomes TCT 2012 Serruys 23 October 2012 Slide 8 48 60
Left Main Disease 5-year Outcomes (N=705) CABG (n=348) P=0.53 P=0.10 TAXUS (n=357) P=0.03 P<0.001 P=0.12 36.9 Patients (%) 31.0 All Death MI CVA Revasc. Mohr FW et al. Lancet 2013;381:629 38 SYNTAX 3VD 5-year Outcomes TCT 2012 Mohr 23 October 2012 Slide 9 MACCE
MACCE to 5 Years by SYNTAX Score Tercile LM Subset High Scores 33 CABG (N=149) TAXUS (N=135) LM Disease MACCE (%) 50 46.5% P=0.003 29.7% 25 0 0 12 24 36 Months 48 60 CABG PCI P value Death 14.1% 20.9% 0.11 CVA 4.9% 1.6% 0.13 MI 6.1% 11.7% 0.13 Death, CVA or MI 22.1% 26.1% 0.40 Revasc. 11.6% 34.1% <0.001 Serruys PW et al. Lancet 2013;381:629 38 SYNTAX 3VD 5-year Outcomes TCT 2012 Serruys 23 October 2012 Slide 10
MACCE to 5 Years by SYNTAX Score Tercile Low to Intermediate Scores (0-32) CABG (N=196) TAXUS (N=221) LM Disease Cumulative Event Rate (%) 50 PCI P value 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 Revasc. 18.6% 22.6% 0.36 P=0.74 32.1% 31.3% 25 0 CABG 0 12 24 36 48 60 Months Since Allocation Serruys PW et al. Lancet 2013;381:629 38 SYNTAX 3VD 5-year Outcomes TCT 2012 Serruys 23 October 2012 Slide 11
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
I d rather die than have a stroke What kind of stroke will I have? A mini-stroke or a Big One???
Most patients prefer repci to the risk of CVA
ACC/AHA Guidelines for Revascularization of Left Main Disease: Pre-2009 I IIa IIb III CABG PCI Kushner et. Al. JACC Vol 54. No 23, 2009 Post-2009 I IIa IIb III CABG PCI
ACC/AHA Guidelines IIa LMCA PCI is reasonable in pts with class III angina and >50% LM stenosis who are not eligible for CABG IIb 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 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 v 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)? v 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*? v 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 @ 165 international sites SYNTAX score 32 Consensus agreement by heart team Yes (N=2600) Enrollment registry R PCI (Xience Prime) (N=1300) No (N=1000) 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
MACCE to 3 Years by SYNTAX Score Tercile LM Subset Low to Intermediate Scores (0-32) CABG (N=196) TAXUS (N=221) Left Main Disease Cumulative Event Rate (%) 40 P=0.45 30 23.2% 20.5% 20 10 0 0 12 24 36 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value Two-year Outcomes of the SYNTAX Trial CABG PCI P value Death 9.0% 3.7% 0.02 CVA 3.3% 0.9% 0.09 MI 2.6% 4.6% 0.33 Death, CVA or MI 13.2% 8.7% 0.12 Revasc. 13.7% 15.7% 0.61 EOC unblinding
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 Clinical and anatomic eligibility for both PCI and CABG by heart team consensus Silent ischemia, stable angina, unstable angina or recent MI 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 mm2, 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 @ 26 EU sites With 3 additional non-complex lesions (excludes length >25 mm, CTO, 2-stent bifurcation, calcified or tortuous vessels) R 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
What Have I Learned from Treating Left Main Bifurcation Lesion in the Last 20 Years? Seung-Jung Park, MD, PhD Professor of Medicine, University of Ulsan College of Medicine Heart Institute, Asan Medical Center, Seoul, Korea
Adjusted Hazard Ratios of MACCE Between CABG and PCI for LM Disease (N=2360) Outcomes of PCI Are Getting Better Over time! P for Interaction = 0.002and Better DES. Mainly due to more IVUS/FFR HR (95% CI) P value BMS (1995-2002) 0.33 (0.23-0.47) <0.001 Early DES (2003-2006) 0.53 (0.35-0.80) 0.005 Late DES (2007-2010) 1.01 (0.68-1.49) 0.32 0.1 PCI better 1 10 CABG better New Data from ASAN MAIN registry, 2014
Treatment for Distal LM Bifurcation Leson
Distal LM Stent Technique Less 2 stent approach P=0.14 100 Percent (%) 80 40.4 33.3 60 40 20 0 66.7 59.6 Before Routine Use of FFR After Routine Use of FFR Two stent Single Stent cross over
Restenosis at 2 year Pooled Analysis in 403 Patients with LM PCI Using SES % Ostial and Shaft Bifurcation PCI Stent Crossover (provisional second stent) Is Clearly Better! 3/67 14/222 29/114 Single Two stent Kang et al. Circ Cardiovasc Interv 2011;4:1168-74
Distal LM Disease, Small LCX, Discrete Narrowing 75/M, Effort Chest Pain, Normal EF
Stent Crossover Predilation with Maverick 2.5mm Resolute Integrity 3.5mm
LCX Jailing, After Stent Crossover Positive FFR, Significant Jailing
Kissing Balloon Inflation! 3.5 mm Balloon Balloon Dilatation With Ryujin 2.0 mm 2.0 mm Balloon
After Kissing Balloon Inflation Negative FFR!
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 DAC: Consider a Nordic Bifurcation approach and only stent if TIMI 2 flow. Ignore How Cx Looks
Salvage Branch with bail-out stenting Reverse Mini crush T-stent Cullotte Final Kissing Balloons important What is main branch?.most choose LM into LAD and salvage Cx. Some few do reverse
An approach for bifurcational lesions when using 2 stents as intention to treat Bifurcational lesion with no disease proximal to the bifurcation or very short left main V-Stent Pre Cross Section Bifurcational lesion with main branch disease extending proximal to the bifurcation and side branch which has origin with about 90 angle Short-Mini Crush/culotte T-Stent Post Pre Bifurcational lesion with main branch disease extending proximal to the bifurcation and side branch which ha origin with about 60 angle Post Pre Post
Chen, SL, et al. J Am Coll Cardiol Extra Step Compared to Mini-Crush Step 1: stenting side branch (mini crush) Step 2: balloon crush (step crush) Step 3: first kissing balloon inflation Step 4: stenting main vessel Step 5: final kissing balloon inflation
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