3Is left main an issue in CABG surgery? Is left main an issue in PCI?
4Is Syntax an all-comers randomized trial Is Syntax an all-comers randomized trial ? Excl: previous CABG, combined surgery and acute MITwo Registry Armsn = 1275CABG = 1077PCI = 198Randomized Armsn=1800CABG = 897PCI-Taxus = 903Heart Team (surgeon & interventionalist)Amenable for only one treatment approachAmenable for bothtreatment options?No, Syntax is no all-comers,The bias is residual in allowing the choice between RCT and registry.A lot of information is hidden in the N of the registries.The H.T. considered that CABG was the only choice for 35 % of patients.The H.T. considered that PCI was the only choice for 6 % of patients.4
6The Syntax one-year primary MACCE is (for power reasons)a combination of biased and non-biased eventswith different weights (lethal and non-lethal).MACCE ARC MACCE definition Circ 2007; 115: :All cause DeathClear unbiased dramatic eventCerebro-vascular Accident (CVA/Stroke)Unbiased dramatic eventAt discharge 50 % of events are symptom freeEqual to death?Method of diagnosis biasedDocumented Myocardial InfarctionUnbiased lab result but difficult interpretationEqual to death? Does a summation with death make any sense?Even in the presence of no HD or echocardiographic changes, sometimes not even a single PVC ?Any Repeat Revascularization (PCI and/or CABG)The drivers to re-ïntervention are unbiased, the event is biased.
8Drivers of re-intervention: survival after return of angina
9Primary Endpoint (12 Month MACCE) Non-inferiority to CABG Difference in MACCE rates(CABG-PCI with TAXUS Express)Zone of Non-inferiorityPre-specified Margin = 6.6%2%4%6%8%10%-2%-4%Non-inferiorInferiorUpper 1-sided 95% confidence intervalsPiaggio et al, JAMA 2006; 295:9
10Syntax RCT Pt data I CABG n=897 TAXUS n=903 P value Age, mean ± SD (y) 65.0 ± 9.865.2 ± 9.70.55Male, %78.976.40.20BMI, mean ± SD27.9 ± 4.528.1 ± 4.80.37Diabetes, %28.528.20.89Hypertension, %77.074.00.14Hyperlipidemia, %77.278.70.44Current smoker, %22.018.50.06Prior MI, %33.831.90.39Unstable angina, %28.028.90.67Additive EuroSCORE, mean ± SD3.8 ± 2.73.8 ± 2.60.7810
11Medically Treated Diabetes is an irrelevant risk factor. Very young patients!Medically Treated Diabetes is an irrelevant risk factor.Only insulin treated diabetes (in Syntax only 7 %) has any impact.
12Syntax RCT Pt data II CABG n=897 TAXUS n=903 P value Total SYNTAX Score29.1 ±11.428.4 ±11.50.19Diffuse disease or small vessels, %10.711.30.69No. lesions, mean ± SD4.4 ±1.84.3 ±1.80.443VD only, %66.365.40.70Left main, any, %33.734.6Left Main only126.96.36.199Left Main + 1 vessel188.8.131.52Left Main + 2 vessel12.011.50.72Left Main + 3 vessel13.513.9Total occlusion, %184.108.40.206Bifurcation, %73.372.40.67Trifurcation, %10.60.9212
13but as staged procedures !! The staged procedures of the PCI were not considered as re-interventions of incomplete proceduresbut as staged procedures !!
15Primary Endpoint:12 months MACCE Non-inferiority analysis Pre-specified Margin = 6.6%5.5%+95% CI = 8.3%Exhibit 15%10%15%20%Difference in MACCEThe criteria for Non-inferiority comparison was not met for the primary endpoint, further comparisons for the LM and 3VD subgroups are observational only and hypothesis generating
22Re- intervention P<0.0001 PCI-CABG Graft revascularization, % CABG n=897At least one arterial graft97.3Arterial graft to LAD95.6LIMA + venous78.1Double LIMA/RIMA27.6Complete arterial revascularization18.9Radial Artery14.1Venous graft only2.6The reïntervention rate within the first year in the CABG group is half the rate in the registry versus in the trial.In the registry were the worst patients situated.
25All-Cause Death to 3 Years TAXUS (N=903)CABG (N=897)P=0.132040Before 1 year*3.5% vs 4.4%P=0.371-2 years*1.5% vs 1.9%P=0.532-3 years*1.9% vs 2.6%P=0.32Before 1 year3.5% vs 4.4%P=0.371-2 years1.5% vs 1.9%P=0.532-3 years1.9% vs 2.6%P=0.32Cumulative Event Rate (%)8.6%6.7%123624Months Since AllocationCumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesITT population
26CVA to 3 Years TAXUS (N=903) CABG (N=897) P=0.07 20 40 Before 1 year*2.2% vs 0.6%P=0.0031-2 years*0.6% vs 0.7%P=0.822-3 years*0.5% vs 0.6%P=1.00Before 1 year2.2% vs 0.6%P=0.0031-2 years0.6% vs 0.7%P=0.822-3 years0.5% vs 0.6%P=1.0Cumulative Event Rate (%)3.4%2.0%123624Months Since Allocation
27Myocardial Infarction to 3 Years TAXUS (N=903)CABG (N=897)P=0.0022040Before 1 year*3.3% vs 4.8%P=0.111-2 years*0.1% vs 1.2%P=0.0082-3 years*0.3% vs 1.2%P=0.03Before 1 year3.3% vs 4.8%P=0.111-2 years0.1% vs 1.2%P=0.0082-3 years0.3% vs 1.2%P=0.03Cumulative Event Rate (%)7.1%3.6%123624Months Since Allocation
28Repeat Revascularization to 3 Years TAXUS (N=903)CABG (N=897)P<0.0012040Before 1 year*5.9% vs 13.5%P<0.0011-2 years*3.7% vs 5.6%P=0.062-3 years*2.5% vs 3.4%P=0.33Before 1 year5.9% vs 13.5%P<0.0011-2 years3.7% vs 5.6%P=0.062-3 years2.5% vs 3.4%P=0.3319.7%Cumulative Event Rate (%)10.7%123624Months Since Allocation
29MACCE to 3 Years TAXUS (N=903) CABG (N=897) P<0.001 20 40 28.0% Before 1 year*12.4% vs 17.8%P=0.0021-2 years*5.7% vs 8.3%P=0.032-3 years*4.8% vs 6.7%P=0.10Before 1 year12.4% vs 17.8%P=0021-2 years5.7% vs 8.3%P=0.032-3 years4.8% vs 6.7%P=0.128.0%Cumulative Event Rate (%)20.2%123624Months Since Allocation
30SyntaxThe interventional cardiologists have shown that it is possible to treat the left main, but have as yet totally failed that this makes sense from a societal and patient perspective.Have their aggressive re-interventions after the primary therapy made any sense? Where is the evidence to re-intervene?The surgeons have shown that they do not control risk by failing inThe no-touch aortaThe more complete arterial revascularizationThe off-pump CABGThe reduction of risk and early reïntervention.