The SYNTAX Message is Clear: CABG is Preferred in Complex MVD Angioplasty Summit TCTAP 2012 Seoul, Korea April 2012 David R. Holmes, MD Mayo Clinic Rochester, MN
Presenter Disclosure Information David R. Holmes, Jr., M.D. The SYNTAX Message is Clear: CABG is Preferred in Complex MVD The following relationships exist related to this presentation: Immediate Past President ACC
Patient Centric Care Stroke Death Myocardial infarction Repeat procedures Sternotomy t
Patient GF 1979: Age 39 was the 16 th patient treated with PTCA at Mayo Clinic 1979 2007: I performed 15 different PCI procedures. 2007: Office visit with patient: It went something like this. 2011: Remains asymptomatic. 3107189-4
What do we know about SYNTAX Constructed to be an all comer study with limitations Carried out in expert centers by expert surgeons and expert interventional cardiologists Extensive disease which pushed the limit of PCI Excellent surgical techniques although postop meds not as optimal Stent selected first generation, results may not be relevant to current technology
Patient in SYNTAX Randomized Controlled Trial Intent-to to-treat CABG n=897 RCT: Enrolled N=1800 PCI * n=903 CABG n=849 RCT: 1 Year Follow-up CABG 94.6% PCI 98.7% PCI * n=891 CABG n=836 RCT: 2 Year Follow-up CABG 93.2% PCI 98.0% PCI * n=885 CABG n=827 RCT: 3 Year Follow-up PCI * CABG 92.2% 2% PCI 98.0% n=885 CABG n=819 RCT: 4 Year Follow-up CABG 91.3% PCI 97.3% PCI * n=879 * TAXUS Express
Overall Randomized Cohort 4-year Outcomes (N=1800) CABG (n=897) TAXUS (n=903) 50 P=0.07 P=0.048 P<0.001 P=0.06 P<0.001 40 Patients (% %) 30 20 10 0 23.0 18.0 14.6 11.7 11.9 8.8 8.3 3.8 37 3.7 23 2.3 Death/CVA/MI Death MI CVA Revasc. Cumulative KM Event Rate; log-rank P value ITT population
All-Cause Death to 4 Years CABG (N=897) TAXUS (N=903) (%) nt Rate 50 Before 1 year * 3.5% vs 4.4% P=0.37 1-2 years * 1.5% vs 1.9% P=0.53 P=0.048 2-3 years * 1.9% vs 2.6% P=0.32 3-4 years * 2.2% vs 3.2% P=0.22 ive Eve umulat C 25 0 11.7% 0 12 24 36 48 Months Since Allocation 8.8% Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population
Myocardial Infarction to 4 Years CABG (N=897) TAXUS (N=903) (%) nt Rate ve Even umulativ Cu 50 25 0 Before 1 year * 3.3% vs 4.8% P=0.11 1-2 years * 0.1% vs 1.2% P=0.008 P<0.001 2-3 years * 0.3% vs 1.2% P=0.03 3-4 years * 0.3% vs 1.5% P=0.01 0 12 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates 8.3% 3.8% ITT population
CVA to 4 Years CABG (N=897) TAXUS (N=903) (%) nt Rate ve Even umulativ Cu 50 25 0 Before 1 year * 2.2% vs 0.6% P=0.003 1-2 years * 0.6% vs 0.7% P=0.82 P=0.06 2-3 years * 0.5% vs 0.6% P=1.00 3-4 years * 0.4% vs 0.2% P=0.68 0 12 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates 3.7% 2.3% ITT population
MACCE to 4 Years CABG (N=897) TAXUS (N=903) (%) nt Rate ve Even umulativ Cu 50 25 0 Before 1 year * 12.4% vs 17.8% P=0.002 1-2 years * 5.7% vs 8.3% P=0.03 P<0.001 2-3 years * 4.8% vs 6.7% P=0.10 3-4 years * 4.2% vs 7.9% P=0.002 33.5% 23.6% 0 12 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population
Repeat Revascularization to 4 Years CABG (N=897) TAXUS (N=903) (%) nt Rate ( ve Even umulativ Cu 50 25 0 Before 1 year * 1-2 years * 2-3 years * 3-4 years * 5.9% vs 13.5% 3.7% vs 5.6% 2.5% vs 3.4% 1.6% vs 4.2% P<0.001 P=0.06 P=0.33 P=0.002 P<0.001 23.0% 11.9% 0 12 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population
Drug-Eluting Stents vs CABG Repeat Revascularization Meta-Analysis EES vs PES HR=0.51, 95% CI 0.39-0.660.66 TLR at 1 Year Trials EES PES RR (95% CI) SYNTAX HR=2.3, 95% CI 1.7-3.1 EES vs CABG? SPIRIT II 4/223 5/77 0.28 (0.08, 1.00) PES SPIRIT III 22/669 18/333 0.61 (0.33, 1.12) EES 6.9 SPIRIT IV 61/2458 55/1229 0.55 (0.39, 0.79) COMPARE 15/897 40/903 0.38 (0.21, 0.68) Overall (I-squared = 0.0%, p = 0.491) 0.51 (0.39, 0.66) NOTE: Weights are from random effects analysis.1.2.5 1 2 5 10 Risk ratio Favors EES Favors PES Kalesan, Juni Updated 8/2011 Serruys PW et al: NEJM 2009
MACCE to 4 Years by SYNTAX Score Tercile Low Scores (0-22) 50 CABG (N=275) TAXUS (N=299) Overall CABG PCI P Death 8.9% 8.3% 0.77 Rate (%) Cumulati ive Event 25 P=0.57 28.6% 26.1% CVA 4.0% 1.4% 0.059 MI 4.2% 6.6% 0.25 Death, CVA or MI 14.6% 14.4% 0.87 Revasc 13.6% 20.0% 0.04 0 0 12 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 15SE 1.5 SE; log-rank P value Site-reported Data; ITT population
MACCE to 4 Years by SYNTAX Score Tercile Intermediate Scores (23-32) 32) ate (%) e Event Ra Cumulative 50 25 CABG (N=300) TAXUS (N=310) P=0.006 006 Overall 32.0% 21.5% CABG PCI P Death 9.3% 11.1% 0.49 CVA 3.6% 2.0% 0.25 MI 36% 3.6% 90% 9.0% 0.009 009 Death, CVA or MI 14.9% 17.3% 0.44 Revasc 10.9% 20.7% 0.002 0 0 12 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value Site-reported Data; ITT population
MACCE to 4 Years by SYNTAX Score Tercile High Scores ( 33) Cumulative Event Ra ate (%) 50 25 CABG (N=315) TAXUS (N=290) P<0.001 Overall 40.1% 23.6% CABG PCI P Death 8.4% 16.1% 0.004 CVA 3.7% 3.5% 0.80 MI 3.9% 9.3% 0.01 Death, CVA or MI 14.6% 22.7% 0.01 Revasc 11.4% 28.8% <0.001 0 0 12 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value Site-reported Data; ITT population
ARC ST Definite ARC ST (Per Patient) Probable ARC ST (Per Patient) 10 8.8 8 Patie ents, % 6 4 2 0 0.3 Acute 1d 2.6 Subacute 2-30d 1.7 Late 31-365d365d 1.3 14 1.4 Very Late 1.1 366-730d 731-1095d 1095d 1096-1460d1460d Total 4 year Days Postprocedure Definite plus probable per ARC definitions (Cutlip, et al. Circulation 2007;115:2344). 1PCI patient had an ST 1d and 6d post-procedure; procedure; therefore, counted in the 1d and 2-30d intervals but only once in the total.
Everolimus-Eluting Eluting vs Paclitaxel-Eluting StentsDES Safety - Risk of Stent Thrombosis Definite ST Definite or Probable ST EES PES RR (95% CI) EES PES RR (95% CI) SPIRIT II 1/223 2/77 0.17 (0.02, 1.88) SPIRIT II 2/223 2/77 0.35 (0.05, 2.41) SPIRIT III 6/669 2/333 1.49 (0.30, 7.36) SPIRIT III 8/669 5/333 0.80 (0.26, 2.42) SPIRIT IV 8/2458 12/1229 0.33 (0.14, 0.81) SPIRIT IV 10/2458 15/1229 0.33 (0.15, 0.74) COMPARE 5/897 5/897 24/903 0.21 (0.08, 0.55) COMPARE 8/897 8/897 35/903 0.23 (0.11, 0.49) Overall (I 2 = 34.6%, p = 0.205) 0.35 (0.16, 0.77) Overall (I 2 = 9.0%, p = 0.348) 0.34 (0.21, 0.57).1.2.5 1 2 5 10 Risk ratio Favors EES Favors PES.1.2.5 1 2 5 10 Risk ratio Favors EES Favors PES N = 6,789 Kalesan, Windecker
Summary and Conclusions Four-year MACCE rates in the overall randomized cohort were significantly higher for PCI than CABG Significant increase of cardiac death, MI and repeat revascularization in PCI vs CABG-treated patients Composite safety (death/stroke/mi) remains not significantly different between arms at 4 years (P=0.07) MACCE rates at 4 years were not significantly different for patients with a low baseline SYNTAX Score; for patients with intermediate or high SYNTAX Scores, MACCE was increased at 4 years in patients treated with PCI The 4-year SYNTAX results suggest that PCI may be an acceptable alternative revascularization method to CABG when treating gp patients with less complex (lower SYNTAX Score) disease including LM disease
SYNTAX and MVD The game is not over We need to know more about causes of death and MI We need to know what a current DES would behave like What about Hybrid procedures with LIMA to LAD and DES to the rest? Still, currently with very severe and extensive disease, CABG appears to be the better option