The Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery: The SYNTAX Study

Transcription

1 The Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery: The SYNTAX Study Five-Year Results in the French Subset René Koning, MD On behalf of the SYNTAX investigators Three-year Results in the French Subset Koning 9-12 October 2011 Slide 1

2 RESULTATS SYNTAX «un 2ème French Paradox!» R. Koning Saint-Hilaire - ROUEN SYNTAX: French Subset Konig FRANCOPHONE October 2012 Slide 2

3 SYNTAX Trial Design 62 EU Sites + 23 US Sites Heart Team (surgeon & interventionalist) Amenable for both treatment options Stratification: LM and Diabetes Amenable for only one treatment approach Randomized Arms N=1800 n=897 vs TAXUS n=903 Two Registry Arms N=1275 n= w/ f/u PCI n=198 all w/ f/u * TAXUS Express Three-year Results in the French Subset Koning 9-12 October 2011 Slide 3

4 Major strengths of the SYNTAX trial Three-year Results in the French Subset Koning 9-12 October 2011 Slide 4

5 Syntax Score Purpose / Validity To describe and quantify the anatomic characteristics of lesions in the context of PCI for SURGICAL candidates. 3VD +/- LM NOT single or two vessel disease. Three-year Results in the French Subset Koning 9-12 October 2011 Slide 5

6 Patients (%) Stent Number and Length Higher in the SYNTAX Trial % of patients received 5 stents Multivessel disease: 96.2%* 3-vessel disease: 90.8% Avg. stents per patient: 4.6 ± 2.3 Avg. stented length: 86.1 mm 5 0 Max # 14 stents! Total Number of Stents Implanted per Patient Three-year Results in the French Subset Koning 9-12 October 2011 Slide 6

7 Cumulative Event Rate (%) MACCE to 5 Years (N=897) TAXUS (N=903) 50 Before 1 year * 12.4% vs 17.8% P= years * 5.7% vs 8.3% P= years * 4.8% vs 6.7% P= years * 4.2% vs 7.9% P= years * 5.0% vs 6.3% P=0.27 P< % % Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population SYNTAX: French Subset Konig FRANCOPHONE October 2012 Slide 7

8 Clinical Sites in France Centre Hôpital Universitaire Rouen/Hôpital Charles Nicolle; Rouen Bessou; PCI Eltchaninoff Clinique Saint-Hilaire Rouen; Rouen Bessou; PCI Berland Institut Jacques Cartier; Massy Farge; PCI Morice Clinique St Augustin; Bordeaux Fernandez; PCI Darremont Centre Hôpital Universitaire Rangueil; Toulouse Fournial; PCI Carrié Clinique Pasteur; Toulouse Soula; PCI Marco/Fajadet Three-year Results in the French Subset Koning 9-12 October 2011 Slide 8

9 Randomized Patient Enrollment non-french Sites N=1592 n=792 PCI n=800 n=105 PCI n=103 N=208 Three-year Results in the French Subset Koning 9-12 October 2011 Slide 9

10 Patients (n) Enrollment in the Randomized Cohort and Registries Rest of Sites France Rest of Sites France Rest of Sites France Randomized Registry PCI Registry Three-year Results in the French Subset Koning 9-12 October 2011 Slide 10

11 Patients Enrolled Per Site French Subset Centre Hôpital Universitaire Rouen, Hôpital Charles Nicolle Clinique St. Augustin Clinique Pasteur Clinique Saint- Hilaire Rouen Centre Hôpital Universitaire Rangueil Institut Jacques Cartier Bessou/ Eltchaninoff Fernandez/ Darremont Soula/ Marco Bessou/ Berland Fournial/ Carrié Arnaud/ Morice French Patients Enrolled per Site Three-year Results in the French Subset Koning 9-12 October 2011 Slide 11

12 Patient Characteristics (I) French Subset N=105 TAXUS N=103 P value Age, mean ± SD (y) 65.8 ± ± Male, % BMI, mean ± SD 26.9 ± ± Medically-treated Diabetes, % Hypertension, % Hyperlipidemia, % Current smoker, % Prior MI, % Unstable angina, % Additive euroscore, mean ± SD 3.7 ± ± Total Parsonnet score, mean ± SD 8.7 ± ± Site-reported data Three-year Results in the French Subset Koning 9-12 October 2011 Slide 12

13 Patient Characteristics (I) French vs non-french Subsets French N=105 non-french N=792 French TAXUS N=103 non-french TAXUS N=800 Age, mean ± SD (y) 65.8 ± ± ± ± 9.5 Male, % BMI, mean ± SD 26.9 ± ± ± ± 4.8 Medically-treated Diabetes, % Hypertension, % Hyperlipidemia, % Current smoker, % Prior MI, % Unstable angina, % Additive euroscore, mean ± SD 3.7 ± ± ± ± 2.6 Total Parsonnet score, mean ± SD 8.7 ± ± ± ± 6.9 Site-reported data Three-year Results in the French Subset Koning 9-12 October 2011 Slide 13

14 Patient Characteristics (II) French Subset Patient-based N=105 TAXUS N=103 P value Total SYNTAX Score 26.7 ± ± Diffuse disease or sm. vessels, % No. lesions, mean ± SD 3.8 ± ± VD only, % Left main, any, % Left Main only Left Main + 1 vessel Left Main + 2 vessel Left Main + 3 vessel Total occlusion, % Bifurcation, % Trifurcation, % Site-reported data Three-year Results in the French Subset Koning 9-12 October 2011 Slide 14

15 Patient Characteristics (II) French vs non-french Subsets Patient-based French N=105 non-french N=792 French TAXUS N=103 non-french TAXUS N=800 Total SYNTAX Score 26.7 ± ± ± ± 10.6 Diffuse disease or sm. vessels, % No. lesions, mean ± SD 3.8 ± ± ± ± 1.7 3VD only, % Left main, any, % Left Main only Left Main + 1 vessel Left Main + 2 vessel Left Main + 3 vessel Total occlusion, % Bifurcation, % Trifurcation, % Site-reported data Three-year Results in the French Subset Koning 9-12 October 2011 Slide 15

16 Procedural Characteristics French Subset: RCT Patient-based N=105 Off-pump surgery, % 4.0 Graft revascularization, % At least one arterial graft 98.0 Arterial graft to LAD 97.0 Double LIMA/RIMA 60.0 Complete arterial revascularization 48.0 Venous graft only 2.0 Grafts per patient, mean ± SD Distal anastomosis/pt, mean ± SD Post-Proced. Hospital Stay, mean ± SD (d) Three-year Results in the French Subset Koning 9-12 October 2011 Slide 16

17 Procedural Characteristics French vs non-french Subsets: RCT Patient-based French N=105 non-french N=792 Off-pump surgery, % Graft revascularization, % At least one arterial graft Arterial graft to LAD Double LIMA/RIMA Complete arterial revascularization Venous graft only Grafts per patient, mean ± SD Distal anastomosis/pt, mean ± SD Post-Proced. Hospital Stay, mean ± SD (d) Three-year Results in the French Subset Koning 9-12 October 2011 Slide 17

18 Procedural Characteristics French Subset: PCI RCT Patient-based PCI N=103 Staged procedure, % 6.9 Post-Proced. Hospital Stay, mean ± SD (d) No. stents implanted, mean ± SD Total length implanted, mm ± SD Range, mm Long stenting (>100 mm), % 22.8 Three-year Results in the French Subset Koning 9-12 October 2011 Slide 18

19 Procedural Characteristics French vs non-french Subsets: PCI RCT Patient-based French TAXUS N=103 non-french TAXUS N=800 Staged procedure, % Post-Proced. Hospital Stay, mean ± SD (d) No. stents implanted, mean ± SD Total length implanted, mm ± SD Range, mm Long stenting (>100 mm), % Three-year Results in the French Subset Koning 9-12 October 2011 Slide 19

20 Patients (%) MACCE at 12 Months French Subset (n=105) TAXUS (n=103) P=0.99 P=0.99 P=0.37 P=0.99 P= All Death MI CVA Revasc. MACCE Three-year Results in the French Subset Koning 9-12 October 2011 Slide 20

21 Patients (%) MACCE at 3 Years French Subset (Francophone 2012) (n=105) TAXUS (n=103) P=0.54 P=0.68 P=0.10 P=0.83 P= All Death MI CVA Revasc. MACCE Three-year Results in the French Subset Koning 9-12 October 2011 Slide 21

22 Cumulative Event Rate (%) CVA (Stroke) to 5 Years French Subset (N=105) TAXUS (N=103) 50 P= % 1.0% Months Since Allocation Event rate ± 1.5 SE, Fisher exact test ITT population SYNTAX: French Subset Konig FRANCOPHONE October 2012 Slide 22

23 Cumulative Event Rate (%) Myocardial Infarction to 5 Years French Subset (N=105) TAXUS (N=103) 50 P= Event rate ± 1.5 SE, Fisher exact test Months Since Allocation 5.0% 4.0% ITT population SYNTAX: French Subset Konig FRANCOPHONE October 2012 Slide 23

24 Cumulative Event Rate (%) Death/CVA/MI to 5 Years French Subset (N=105) TAXUS (N=103) 50 P= % 13.7% Months Since Allocation Event rate ± 1.5 SE, Fisher exact test ITT population SYNTAX: French Subset Konig FRANCOPHONE October 2012 Slide 24

25 Cumulative Event Rate (%) Revascularization to 5 Years French Subset (N=105) TAXUS (N=103) 50 P= % 20.3% Months Since Allocation Event rate ± 1.5 SE, Fisher exact test ITT population SYNTAX: French Subset Konig FRANCOPHONE October 2012 Slide 25

26 Cumulative Event Rate (%) MACCE to 5 Years French Subset (N=105) TAXUS (N=103) 50 P= % 28.9% Months Since Allocation Event rate ± 1.5 SE, Fisher exact test ITT population SYNTAX: French Subset Konig FRANCOPHONE October 2012 Slide 26

27 Patients (%) MACCE at 5 Years French Subset (n=105) TAXUS (n=103) P=0.49 P=0.77 P=0.03 P=0.93 P= ,8 20,3 12,8 9,9 7,0 5,0 4,0 1,0 All Death MI CVA Revasc. MACCE Three-year Results in the French Subset Koning 9-12 October 2011 Slide 27

28 Symptomatic Graft Occlusion & Stent Thrombosis to 5 Years French Subset Patients (%) (n=105) TAXUS (n=103) 10,0 9,0 8,0 7,0 6,0 5,0 4,0 3,0 2,0 1,0 0,0 P=0.09 7,4 2,3 n=7 n=2 TAXUS Three-year Results in the French Subset Koning 9-12 October 2011 Slide 28

29 Patients (%) Patients (%) Outcome According to Geographic Location at 3 Years (Francophone 2011) 35 TAXUS TAXUS Death/CVA/MI MACCE French Subset n=208 non-french n=1592 Three-year Results in the French Subset Koning 9-12 October 2011 Slide 29

30 Patients (%) Patients (%) Outcome According to Geographic Location at 5 Years 50 TAXUS 50 TAXUS 40 34, , ,6 13,7 28, ,4 21,8 25, Death/CVA/MI MACCE Death/CVA/MI MACCE French Subset n=208 non-french n=1592 Three-year Results in the French Subset Koning 9-12 October 2011 Slide 30

31 Patients (%) Patients (%) Outcome According to Geographic Location at 5 Years - Safety TAXUS 34,6 28,9 18,6 13, TAXUS P=0.36 P=0.39 P=0.01 P< ,4 25,9 21,8 16,4 0 0 Death/CVA/MI MACCE Death/CVA/MI MACCE French Subset n=208 non-french n=1592 Three-year Results in the French Subset Koning 9-12 October 2011 Slide 31

32 Patients (%) Patients (%) Outcome According to Geographic Location at 5 Years -Revasc P=0.93 TAXUS 40,0 35,0 TAXUS P< ,8 20,3 30,0 25,0 20,0 26, ,0 12, ,0 5 5,0 0 0,0 Revasc Revacs French Subset n=208 non-french n=1592 Three-year Results in the French Subset Koning 9-12 October 2011 Slide 32

33 12m MACCE in TAXUS Arm Linear Increase in MACCE by Number of Stents in the SYNTAX Trial 0,30 0, Stents Typical Real World Average 4.6 Stents SYNTAX Average 17.8% Avg. in pts with 5-8+ stents in SYNTAX 19.6% 0,20 0,15 1 stent 5.6% 0,10 0,05 12m MACCE Probability 12m MACCE Rate 0, Number of Stents Implanted Three-year Results in the French Subset Koning 9-12 October 2011 Slide 33

34 MOINS DE CORONAROPATHIE! FIRST FRENCH PARADOX SYNTAX: French Subset Konig FRANCOPHONE October 2012 Slide 34

35 MOINS DE MACCE! THE SECOND FRENCH PARADOX! SYNTAX: French Subset Konig FRANCOPHONE October 2012 Slide 35

36 Conclusions In this post-hoc, hypothesis generating, subset analysis The French randomized SYNTAX cohort, MACCE and the overall safety outcomes (Death, CVA, MI,) were similar in and PCI patients at 5 years. This is contrary to the statistically significant findings in favour of for the non-french subset. The rate of revascularization was similar in the PCI and arms ( 20.8 % vs TAXUS 20.3%) in contrast to the marked difference in the non-french cohort The rate of CVA was statistically higher in the group ( 7.0 vs TAXUS 1.0%) Per protocol rates of symptomatic graft occlusion and stent thrombosis were numerically lower in the TAXUS arm ( 7.4% vs TAXUS 2.3%) 5 year Left Main and 3VD subsets for the overall randomised cohort will be presented at TCT 2012 Three-year Results in the French Subset Koning 9-12 October 2011 Slide 36