Michael Mack, M.D. Baylor Healthcare System Heart Hospital Baylor Plano Dallas, TX

Transcription

1 Michael Mack, M.D. Baylor Healthcare System Heart Hospital Baylor Plano Dallas, TX

2 Maquet, Inc.,- unpaid consultant Cordis, Inc.,- unpaid consultant Boston Scientific, Inc.,- travel expenses paid for Syntax Trial Steering Committee meetings

3 SYNTAX Trial Design 62 EU Sites + 23 US Sites Randomized Arms N=1800 CABG n=897 3VD 66.3% Heart Team (surgeon & interventionalist) Amenable for both treatment options LM 33.7% vs TAXUS * n=903 3VD 65.4% Stratification: LM and Diabetes LM 34.6% Two Registry Arms N=1275 CABG n=1077 5yr f/u n=649 Amenable for only one treatment approach no f/u n=428 PCI n=198 * TAXUS Express SYNTAX: Trial Design and Philosophy Serruys TCT 14 October 2008 Slide 3

4 SYNTAX enrollment: 3,075 Patients at 85 sites in 18 countries 15% 85%

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6 Cumulative Event Rate (%) MACCE to 2 Years CABG (N=897) TAXUS (N=903) P< Before 1 year * 12.4% vs 17.8% P=0.002 After 1 year * 5.7% vs 8.3% P= % 16.3% Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*binary rates ITT population SYNTAX: Trial Design and Philosophy Serruys TCT 14 October 2008 Slide 6

7 SO, IS THAT THE END OF THE DEBATE? SYNTAX: Trial Design and Philosophy Serruys TCT 14 October 2008 Slide 7

8 Why This Is Not The Final Answer Major Dfference in MACCE is Repeat Revascularization

9 There is Left Main Disease and Left Main Disease

10 SINCE THE PRE-DEFINED ENDPOINT WAS NOT ACHIEVED, POST-HOC STRATIFICATION IS NOT PERMISSIBLE. Therefore, further comparisons for the LM and 3VD subgroups are observational only and hypothesis generating

11 EXCEL Evaluation of Xience Prime versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization

12 EXCEL: Study Design Draft design 4000 pts with left main disease SYNTAX score 32 Consensus agreement by heart team PCI (Xience Prime) (N=1250) Yes (N=2500) R CABG (N=1250) No (N=1500) PCI and CABG registries (limited in-hosp data) Clinical follow-up: 30 days, 6 months, yearly through 5 years This trial design has not yet been reviewed by the US FDA and is subject to change

13 Issues With CABG Lessons from SYNTAX Mortality Stroke Atrial Fibrillation Arterial Grafting Graft Patency Trial Participation

14 Cumulative Event Rate (%) All-Cause Death/CVA/MI to 2 Years CABG (N=897) TAXUS (N=903) P= Before 1 year * 7.7% vs 7.6% P=0.98 After 1 year * 2.2% vs 3.5% P= % 9.6% Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*binary rates ITT population SYNTAX: Trial Design and Philosophy Serruys TCT 14 October 2008 Slide 14

15 Cumulative Event Rate (%) All-Cause Death to 2 Years CABG (N=897) TAXUS (N=903) P= Before 1 year * 3.5% vs 4.4% P=0.37 After 1 year * 1.5% vs 1.9% P= % 4.9% Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population SYNTAX: Trial Design and Philosophy Serruys TCT 14 October 2008 Slide 15

16 SYNTAX: Trial Design and Philosophy Serruys TCT 14 October 2008 Slide 16

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19 In SYNTAX, with CABG one is trading a stroke for repeat revascularization. As a patient, who wouldn t want to risk repeat revascularization with PCI rather than a stroke with CABG Common interventional cardiologist s interpretation of Syntax results

20 Cumulative Event Rate (%) CVA to 2 Years CABG (N=897) TAXUS (N=903) P= Before 1 year * 2.2% vs 0.6% P=0.003 After 1 year * 0.6% vs 0.7% P= Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*binary rates 2.8% 1.4% ITT population SYNTAX: Trial Design and Philosophy Serruys TCT 14 October 2008 Slide 20

21 Background Risk of Stroke Neurological deficit > 72 hours In hospital/ 30 days CABG STS Database , n= 774,881 Stroke =1.4% PCI NCDR Database, , n=706,782 Stroke = 0.22 %

22 Patients with Stroke in SYNTAX Randomized Cohort, Intent-to-Treat Enrolled N=1800 CABG n=897 TAXUS * n=903 1 Year Follow-up N=1740 (96.7%) CABG n=849 Stroke n=19 TAXUS * n=891 Stroke n=5 * TAXUS Express

23 Syntax September 3, 23 Timing of Stroke CABG PCI Total 25 (2.8%) 12 (1.4%) Pre-procedure 3 (0.3%) 0 Procedural- 30 days 9 (1%) 2 (0.2%) 30 days- 1 Year 7 (0.8%) 3 (0.3%) 1-2 years 6 (0.6%) 7 (0.7%)

24 Syntax September 3, 24 Timing of Stroke CABG PCI Total 25 (2.8%) 12 (1.4%) Pre-procedure 3 (0.3%) 0 Procedural- 30 days 9 (1%) 2 (0.2%) 30 days- 1 Year 7 (0.8%) 3 (0.3%) 1-2 years 6 (0.6%) 7 (0.7%)

25 Procedural Characteristics Potential Risk Factors for Stroke CABG N=897 TAXUS N=903 P value Urgent Procedure, % Emergent Procedure, % Time to procedure, d, mean ± SD 17.4 ± ± 13.0 <0.001 Off-pump surgery % Off Pump On Pump P value Stroke 1/134 (0.7%) 18/763 (2.3%) ns Site-reported data Allocation to procedure For PCI patients, includes time for staged procedure

26 Ascending Aortic Atherosclerosis

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28 Medications Potential Risk Factors for Stroke Pre/periprocedural Medication CABG N=897 TAXUS N=903 P value Aspirin, % <0.001 Heparin (unfractionated), % <0.001 Heparin (low molecular weight), % Bivalirudin, % <0.001 Thienopyridine, % <0.001 Aprotinin, % Medication at Discharge Aspirin, % <0.001 Thienopyridine, % <0.001 Coumadin, % <0.001 Statin, % Site-reported data

29 Medications at 12 Months Potential Risk Factors for Stroke CABG N=897 TAXUS N=903 P value Aspirin, % <0.001 Statin, % Beta blockers, % ACE inhibitors, % Thienopyridines, % <0.001 Diuretics, % Calcium channel blockers, % Angiotensin II receptor antagonists, % Nitrates <0.001 Oral antidiabetic, non insulinsensitizer, % H2-receptor blockers, % Medications taken by 10% of patients in either group Site-reported data

30 Causes/ Remedies of Stroke in Syntax Preoperative -3 Minimize time from randomization to surgery Intraoperative -6 Epiaortic Scanning on all patients No touch aortic technique if positive Off pump in high risk patients Postoperative < 30 day- 3 Aggressive management of atrial fibrillation Anticoagulation of PAF??? Dual anti-platelet therapy (DAPT)???? Postoperative >30 days -7 DAPT???

31 Arterial Grafting in SYNTAX Bilateral IMA All Arterial Overall 27% 18% U.S. 10% 5%

32 The SYNTAX-LE MANS Study Synergy Between PCI with TAXUS Express and Cardiac Surgery: Late (15-month) Left Main Angiographic Substudy A. Pieter Kappetein, MD, PhD Erasmus MC, Rotterdam, NL

33 Patient Population De novo disease Limited Exclusion Criteria Previous Coronary Intervention Acute MI with Creatine Kinase>2x Concomitant Cardiac Surgery Left Main Disease (isolated, +1, +2 or +3 vessels) 3 Vessel Disease (revasc all 3 vascular territories) LE MANS Substudy (patients provided separate informed consent)

34 SYNTAX-LE MANS Trial Design All RCT patients with LM 271 patients consented at 49 sites (13 US, 36 EU) CABG N=115 TAXUS N=156 3 pts died * 15 mo angio performed CABG N=115 TAXUS N= mo angio analyzed CABG N=114 TAXUS N=149 * 2 cardiac death: 1 cardiomyopathy and 1 sudden cardiac death

35 Grafts (%) Patients (%) Principal Results CABG Cohort Primary Endpoint (Per graft): 50% to <100% =100% Per patient: 50% to <100% =100% 20 16% 30 27% 6% (15/262) 20 9% (10/114) 10 10% (26/262) 10 18% (21/114) 0 Obstruction/occlusion Ratio at 15 mo (per graft) 0 Obstruction/occlusion Ratio at 15 mo* (per patient) Definitions: Occlusion Ratio: ratio of 50% obstructed or 100% occluded grafts/anastomoses (visual estimate) to the number of grafts/anastomoses placed *Proportion of patients with at least 1 obstructed/occluded graft

36 Patients (%) MACCE at 15 Months CABG Cohort 10 9% MACCE 5% Death/ CVA/MI 0% Death (all-cause) 3% 3% 4% 10/114 6/114 3/114 3/114 5/114 CVA MI Revasc Analysis includes results from all lesions.

37 Graft Obstruction/Occlusion Not Associated With MACCE at 15 Mo CABG Cohort P= <50% Graft Stenosis 50% Graft Stenosis 91% 9% % 10% 75/82 7/ /31 3/31 No MACCE MACCE No MACCE MACCE

38 Patients (%) Patients (%) Principal Results TAXUS Cohort Primary Endpoint: % % 90% /145 <50% stenosis at 15 mo 0 47/48 87/97 LM Non-distal LM Distal <50% stenosis at 15 mo Definitions: Diameter stenosis was assessed by QCA

39 Patients (%) MACCE at 15 Months TAXUS Cohort % 9% MACCE 6% Death/ CVA/MI 2% Death (allcause) 1% 4% 20/156 10/156 3/156 2/156 6/156 14/156 CVA MI Revasc Analysis includes results from all lesions.

40 Stent Patency Significantly Associated With MACCE at 15 Months TAXUS Cohort P= <50% Diameter Stenosis 50% Diameter Stenosis 91% % 55% % 12/134 MACCE / /11 6/11 No MACCE MACCE No MACCE

41 Conclusions CABG Cohort 10% of LM placed grafts/anastomoses were 100% occluded at 15 months post-procedure and an additional 6% were 50% obstructed 54% of patients had complete revascularization * of LM & LM territory at 15 months (baseline 65%) Graft obstruction/occlusion in grafts bypassing LM lesion(s) was not significantly associated with MACCE at 15 months * Note that definitions of complete revascularization differ between treatments and should not be compared.

42 Conclusions TAXUS Cohort 92% of treated LM lesion(s) had <50% stent stenosis at 15 months post-procedure Restenosis more common with LM distal lesions than with LM non-distal lesions 53% complete revasc of LM & LM territory (baseline 67%) *, 1% thrombus, and 0% aneurysm at 15 months Minimal Late Loss in non-distal LM lesions at 15 months In-stent stenosis was significantly associated with MACCE at 15 months *Note that definitions of complete revascularization differ between treatments and should not be compared.

43 JACC January, 2009

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47 Issues With CABG Lessons from SYNTAX < 1% is achievable Mortality- Strokeshould be a rare event < 0.5% Atrial Fibrillationanticoagulation/DAPT/aggressive management Arterial Graftingbenefit clearly demonstrated with BIMA yet use <10% in U.S. Graft Patencycompletion angiography, arterial grafting, DAPT?? Trial Participationour best chance for a level playing field