Multivessel Coronary Artery Disease: Bypass Surgery. Bruce Lytle, MD

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Multivessel Coronary Artery Disease: Bypass Surgery Bruce Lytle, MD

Coronary Artery Bypass Surgery Prolongs Survival Angiographic Subgroups MR (%) LMT stenosis (> 50%) 68% 3V CAD (> 50%) 42% 1/2V CAD and proximal LAD (> 50%) 32% no proximal LAD -5%

Coronary Artery Bypass Surgery Prolongs Survival The more severe the coronary disease, symptoms, and LV dysfunction, the greater the survival benefit of surgery over medical therapy.

Coronary Artery Bypass Surgery Improves Quality of Life Independent of Severity of CAD Angina Increase in exercise capacity Decrease in antianginal medications

Randomized Studies versus Mostly low risk patients Mostly normal LV function Mostly 2 vessel CAD Insufficient numbers of patients with extensive CAD

Cumulative Event Rate (%) MACCE to 4 Years 3VD Subset 50 Before 1 year * 11.5% vs 19.2% P 1-2 years * 4.4% vs 7.0% P=0.08 2-3 years * 4.6% vs 7.4% P=0.06 3-4 years * 2.8% vs 7.7% P P TAXUS (N=546) 33.7% 25 21.0% (N=549) 0 0 12 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population

Cumulative Event Rate (%) All-Cause Death to 4 Years 3VD Subset 50 Before 1 year * 2.9% vs 4.5% P=0.18 1-2 years * 1.2% vs 2.1% P=0.25 2-3 years * 1.7% vs 3.2% P=0.12 3-4 years * 1.7% vs 2.5% P=0.40 P=0.01 25 TAXUS (N=546) 11.9% 0 0 12 24 36 48 Months Since Allocation (N=549) 7.3% Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population

Cumulative Event Rate (%) Repeat Revascularization to 4 Years 3VD Subset 50 Before 1 year * 5.5% vs 14.6% P 1-2 years * 2.8% vs 3.9% P=0.35 2-3 years * 2.5% vs 3.0% P=0.63 3-4 years * 0.6% vs 4.4% P P 25 TAXUS (N=546) 22.8% 10.2% 0 0 12 24 36 48 Months Since Allocation (N=549) Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population

Cumulative Event Rate (%) Myocardial Infarction to 4 Years 3VD Subset 50 Before 1 year * 2.7% vs 5.2% P=0.04 1-2 years * 0.2% vs 1.2% P=0.12 2-3 years * 0.4% vs 1.0% P=0.45 3-4 years * 0.0% vs 2.3% P=0.001 P 25 (N=549) TAXUS (N=546) 9.0% 0 3.3% 0 12 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population

Cumulative Event Rate (%) CVA to 4 Years 3VD Subset 50 Before 1 year * 1.9% vs 0.7% P=0.09 1-2 years * 0.4% vs 0.8% P=0.69 2-3 years * 0.6% vs 0.8% P=1.00 3-4 years * 0.4% vs 0.2% P=0.62 P=0.53 25 (N=549) TAXUS (N=546) 3.4% 2.8% 0 0 12 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population

Cumulative Event Rate (%) MACCE to 4 Years by SYNTAX Score Tercile Intermediate Scores (23-32) 3-vessel Disease P value 50 P=0.0006 TAXUS (N=207) 33.3% Death 12.4% 18.6% 0.048 CVA 3.6% 2.5% 0.53 25 MI 3.1% 10.5% 0.004 0 17.9% (N=208) 0 12 24 36 48 Months Since Allocation Death, CVA or MI 12.4% 18.6% 0.09 Revasc. 8.3% 21.0% 0.0005 Cumulative KM Event Rate ± 1.5 SE; log-rank P value Site-reported Data; ITT population

Cumulative Event Rate (%) MACCE to 4 Years by SYNTAX Score Tercile High Scores ( 33) 50 3-vessel Disease P=0.0009 37.9% TAXUS (N=155) P value Death 6.5% 14.5% 0.02 CVA 2.6% 5.1% 0.31 25 0 21.2% (N=166) 0 12 24 36 48 Months Since Allocation MI 1.9% 7.9% 0.01 Death, CVA or MI 11.0% 22.3% 0.008 Revasc. 11.2% 26.7% 0.0005 Cumulative KM Event Rate ± 1.5 SE; log-rank P value Site-reported Data; ITT population

ASCERT Trial 2/3 V CAD: 2004-2007 189,793 Total

Proportion Surviving IPW Adjusted Survival 1.0 Age >75 Age <75 0.9 0.8 0.7 RR =.77 at 4 years 0.6 RR =.78 at 4 years 0.5 0 500 1,000 1,500 0 500 1,000 1,500 Days from Index Procedure

Proportion Surviving IPW Adjusted Survival 1.0 Men Women 0.9 0.8 0.7 0.6 RR =.81 RR =.76 0.5 0 500 1,000 1,500 0 500 1,000 1,500 Days from Index Procedure

Proportion Surviving IPW Adjusted Survival 1.0 No Diabetes Diabetes: No Insulin Diabetes: Insulin 0.9 0.8 0.7 0.6 RR =.81 RR =.78 RR =.72 0.5 0 500 1,000 1,500 0 500 1,000 1,500 0 500 1,000 1,500 Days from Index Procedure

Proportion Surviving IPW Adjusted Survival 1.0 EF<30 EF 30-49 EV>50 0.9 0.8 0.7 0.6 0.5 RR =.70 RR =.70 RR =.84 0.4 0 500 1,000 1,500 0 500 1,000 1,500 0 500 1,000 1,500 Days from Index Procedure

Proportion Surviving IPW Adjusted Survival 1.0 GFR<30 GFR 31-60 GFR>60 0.9 0.8 0.7 0.6 0.5 0.4 RR =.83 0 500 1,000 1,500 RR =.79 RR =.74 0 500 1,000 1,500 0 500 1,000 1,500 Days from Index Procedure

Emilia-Romagna Registries July 2002 Dec 2008 (REAL) 6246 (RERIC) Surgery 5504 Excluded STEMI, Previous Revasc All had either LMCA, Two other vessels or both

Cumulative rate of Death (%) and DES only in Propensity Score Matched Sample Death 40 30 20 DES 10 0 0 12 24 36 48 60 Months

Hazard Ratio of Death at Five-years Subgroups No. deaths/total no. (%) Hazard ratio (95% CI) P valve Overall Age <55 yr >55 yr Sex Female Male No. vessles diseased 1 with LMCA 2. Without LMCA 2. With LMCA 3. Wihtout LMCA 3. With LMCA LEVF >36% <35% Previous MI No Yes CHF No Yes Diabetes No Yes CVD No Yes CRF No Yes COPD No Yes Malignancy No Yes 587/2702 (20.3) 90/967 (9.3) 470/1,776 (36.5) 142/614 (23.1) 410/2.128 (19.3) 21/65 (32.3) 101/671 (15.1) 80/269 (29.7) 272/1407 (19.3) 70/154 (45.5) 501/2583 (19.4) 73/154 (45.5) 330/1,891 (17.5) 252/611 (31.1) 347/2.204 (15.7) 215/523 (41.1) 352/1,998 (17.8) 219/730 (30.0) 445/2,392 (15.7) 105/364 (28.8) 483/2,581 (15.7) 75/139 (54.0) 457/2,508 (15.2) 86/222 (35.7) 511/2,636 (10.4) 45/108 (42.8) 422/2,762 (15.3) 69/967 (7.1) 361/1776 (20.3) 109\614 (17.8) 314/2,128 (14.8) 17/65 (26.2) 99/671 (14.8) 51/269 (19.0) 198/1407 (14.1) 36/154 (23.4) 376/2,583 (14.6) 43/142 (30.3) 228/1,891 (12.1) 163/811 (22.6) 267/2,204 (12.1) 144/523 (27.5) 272/1,998 (13.6) 151/730 (20.7) 355/2,392 (13.9) 88/364 (24.2) 355/2,581 (13.6 52/130 (37.4) 34/2,506 (13.6) 70/222 (31.5) 1.55 (1.42-1.70) 1.52 (1.09-2.13) 1.56 (1.36-1.80) 1.59 (1.24-2.04) 1.52 (1.33-1.77) 1.37 (0.72-2.59) 1.21 (0.92-1.61) 1.96 (1.35-2.56) 1.51 (1.33-1.94) 2.49 (1.68-3.69) 1.59 (1.38-1.82) 2.24 (1.51-3.33) 1.71 (1.44-2.03) 1.66 (1.37-2.00) 1.57 (1.33-1.85) 1.85 (1.49-2.28) 1.49 (1.27-1.76) 1.78 (1.44-2.20) 1.59 (1.37-1.83) 1.43 (1.06-1.93) 1.64 (1.42-1.89) 1.67 (1.15-2.42) 1.0 (1.38-65) 1.43 (1.03-1.07) 379/2,636 better (14.4) better 1.0 (1.30-1.83) 39/108 (38.1) 1.37 (0.01-2.08) 0.1 1.0 10.0 0.014 0.338 0.176 0.02 0.007 0.007 0.032 0.136 Mortality logarithmic scale

Why is Surgical Revascularization More Effective Than? More Complete Less Negative impact on native vessel Better patency (ITA) Improved vein graft function More protection against progression of atherosclerosis

Lesions Causing Clinical Event 25 20 % Hazard Rate 15 10 5 0 Non-Target Lesion Event Target Lesion Event Cutlip et al: Circ. 2004 1 2 3 4 5 Year

What about simpler 3VD? has not been shown to prolong survival rate except for AMI Syntax has a 4 year F/U Curves are still diverging

Surgery and are not equivalent treatments, and the differences are not just completeness of revascularization

Multivessel Treatment There is no evidence that stenting prolongs the life expectency of any patient with chronic coronary artery disease. There is evidence that surgery does prolong the life expectency of some patients with CAD When we think prognosis is the issue, surgery should be the choice

Multivessel Paradigm Intervention until it is no longer possible, then surgery Surgery with intervention used to treat progression of disease

Follow-up (year) Survival - MVD Favors PTCA p=0.018 Favors 1 3 5 8-5 0 5 10 Survival Risk Difference (%) JACC: 2003