Controversies in Cardiac Surgery

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1 Controversies in Cardiac Surgery 3 years after SYNTAX : Percutaneous Coronary Intervention for Multivessel / Left main stem Coronary artery disease Pro ESC Congress 2010, 28 August 1 September Stockholm Marie-Claude MORICE, MD, FESC, FACC Massy, France

2 Introduction The optimal revascularization strategy for multivessel disease and Left main stenosis is controversial for long time. Technical innovations are faster than performance of clinical trials, making results of randomized studies outdated at the time of appearance.

3 SYNTAX trial: The Reality SYNTAX represents only a minority of daily patients in a catheterization laboratory. It excluded patients with one or Two-vessel disease and those with an acute coronary syndrome in whom PCI has demonstrated to improve prognosis. SYNTAX represents only a minority of daily patients in a catheterization laboratory

4 Revascularization of CAD in perspective Acute Coronary Syndromes In the acute phase of NSTEMI-ACS/STEMI, PCI is preferred revascularisation procedure, CABG is performed in only 2% of patients. About 50% of PCI are performed for ACS Alexiou K et al. Clin Res Cardiol.2008; 97(9): Van de Werf F et al. Eur Heart J.2008; 29:

5 knowledge available prior to SYNTAX trial: Stable CAD Revascularization - in the failure of medical therapy or moderate to large amounts of inducible ischemia Single- or two-vessel disease PCI is the preferred revascularization method Three-vessel disease or left main stenosis, PCI and CABG have similar overall mortality. PCI has more reinterventions, Conflicting data on the impact of diabetes mellitus

6 Stable coronary artery disease Three-vessel disease and left main disease In patients with reduced left ventricular function, CABG is considered being the gold standard based on clinical trials conducted in the 1970s and 1980s. Questionable if we compare historical data with modern, optimal medical therapy which has improved over the last decades. Takaro T et al. Circulation 54(suppl III)1976:III-107 III-117 Yusuf S et al. Lancet.1994; 344:

7 23 randomized trials with 9,963 patients. The difference in survival after PCI or CABG was less than 1% over 10 years of follow-up. Repeated revascularization was more common after PCI than after CABG (risk difference, 24% at 1 year and 33% at 5 years). Bravata DM et al. Ann Intern Med.2007; 147:

8 Stroke risk Procedure-related strokes were more common after CABG than after PCI Bravata DM et al. Ann Intern Med.2007; 147:

9 Five-year survival with balloon angioplasty or stents versus coronary artery bypass grafting (CABG) in patients with multivessel disease (MVD). Bravata DM et al. Ann Intern Med.2007; 147:

10 Five-year survival in patients with diabetes. Survival did not differ between PCI and CABG for patients with diabetes in the six trials. Bravata DM et al. Ann Intern Med.2007; 147:

11 10 randomized trials with 7,812 patients. No overall difference in mortality between CABG and PCI (Mortality rates - 15 vs. 16% over a median follow-up time of 5.9 years). Hlatky MA et al. Lancet.2009; 373:

12 Outcomes of treatment with coronary artery bypass graft or percutaneous coronary intervention Overall unadjusted mortality (A) and composite endpoint of death or myocardial infarction (B) after randomization to CABG or PCI. Hlatky MA et al. Lancet.2009; 373:1190

13 Left Main Stenosis Until now, no large randomized trial compared the outcomes of patients with isolated left main stenosis. However, many recent trials suggested the safety of PCI in this indication. Kereiakes D et al.circulation.2006; 113(21): Moses JW et al.j Am Coll Cardiol.2009; 54(16):

14 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 Two Registry Arms N=1275 CABG n=897 vs TAXUS * n=903 CABG n=1077 PCI n=198 3VD 66.3% LM 33.7% 3VD 65.4% LM 34.6% 5yr f/u n=649 no f/u n=428 * TAXUS Express Serruys PW, Morice MC et al. N Engl J Med :961

15 Major strengths of the SYNTAX trial Contrast to previous trials where only 5% of eligible patients were randomized, All comer trial with few exclusion criteria (in fact, 71% of screened patients were included into the study). decision to randomise a patient into the study was made by a heart team, - an invasive cardiologist and a cardiac surgeon. Serruys PW, Morice MC et al. N Engl J Med :

16 Hypothesis of SYNTAX PCI is not inferior to CABG with respect to the combined endpoint (MACCE), throughout the 12- months period after randomization. However, the primary outcome of SYNTAX rejected this hypothesis With a significantly higher combined event rate of 17.8% in the PCI group versus 12.4% in the CABG group PCI was statistically not non inferior Serruys PW, Morice MC et al. N Engl J Med :

17 Looking results in detail Endpoint(s) Are the components of the combined endpoint are of same relevance or is there a hierarchy of importance? Subgroups Do the results differ between various subgroups, especially those being predefined? Technical considerations Do revascularization techniques used for either PCI or CABG in SYNTAX differ from what is now thought to be optimal?

18 Endpoint(s) The combined endpoint was basically driven by a reduction of repeated revascularization procedures with CABG (5.9 vs. 13.5%) Death and myocardial infarction at most demonstrated a nonsignificant trend. Stroke rates significantly higher with CABG compared to PCI (2.2 vs. 0.6%). Combining all hard events with long-lasting consequences (death, myocardial infarction, stroke), event rate is nearly identical in the PCI group (7.6%) and in the CABG group (7.7%).

19 Absolute difference in 12 months clinical event rate in the SYNTAX trial: All Patients PCI better CABG better PCI better CABG better Reichenspurner,Clin Res Cardiol july 2010

20 Repeat Revascularization vs CABG Repeat Revascularization CABG In 80% of patients randomized to PCI, repeated revascularization was a new PCI. Neuro-cognitive decline - adverse events, which not included in the combined study end point. repeated PCI procedures - inconvenient due to another short hospital stay, More invasive than PCI with more patient discomfort due to open chest surgery but are not necessarily serious or with further sequelae SYNTAX trial, post-procedural hospital stay was significantly prolonged in the CABG group (9.5 ± 8.0 vs. 3.4 ± 4.5 days) Feldman TE. Presented at TCT 2009

21 Criticism of the SYNTAX trial Short duration of follow-up (only 1 year) Late stent thrombosis after DES implantation, leading to myocardial infarction or death and long term beneficial effects of arterial grafts may diverge hard events, in favor for CABG in the long term follow-up ( 0.5,0.6%/year) 2-years follow-up of SYNTAX, no significant difference in hard clinical events (death, MI, stroke) at 2 years (10.8% PCI, 9.6% CABG). Kappetein AP, for the SYNTAX investigators (2009).Presented at ESC

22 Long term Follow ups and End Points: Recent meta analyses comparing PCI [BMS/DES] with bypass surgery No diverge of hard events throughout 3 years. Follow-up to 8 years, there was no significant difference in death or MI between PCI (BMS) and CABG. With respect to DES, 5-year follow-up of the ARTS II trial, did not demonstrate a difference in hard end points between DES and CABG. Daemen J et al. Circulation.2008; 118: Hannan EL et al. N Engl J Med :

23 Sub Groups Analysis SYNTAX is a major, landmark study that aims to provide evidence-based, contemporary, objective randomized data about revascularization of 3VD and LM patients Serruys PW, Morice MC et al. N Engl J Med.2009; 360:

24 Absolute difference in 12 months clinical event rate in the SYNTAX trial: Left main Disease Patients with left main disease and low or intermediate Syntax score had benefit from PCI. Serruys PW, Mohr FW. presented at TCT 2008

25 Left main disease: Syntax Trial Breakthrough in interventional therapy of unprotected left main disease. For the first time, clinical efficacy was proven in a large randomized controlled trial: 1/3 of included patients with left main disease No difference in MACCE after 12 months between PCI and CABG Low and intermediate Syntax score may be have better outcome by PCI. Serruys PW, Morice MC et al. N Engl J Med.2009; 360:

26 Absolute difference in 12 months clinical event rate in the SYNTAX trial: Three vessel disease population Low SYNTAX score in three vessel disease can switch the pendulum back towards PCI

27 Absolute difference in 12 months clinical event rate in the SYNTAX trial: Diabetes Mellitus

28 Three-vessel disease and diabetes Death, MI and stroke higher for diabetic patients, but true for PCI and CABG. Reduction of MACCE with CABG compared to PCI was more pronounced than in the overall study population. So presence of diabetis must be weighted in favor of bypass surgery, when making a decision about revascularization strategy except for low Syntax score. Banning AP et al. J Am Coll Cardiol,2010

29 Subgroups and Heart Team decision making Revascularization strategy cannot be based on belonging to a single subgroup characteristics. Discussion between surgeons and cardiologists to integrate all these factors into one decision, which best matches the need of the patient. Patient s age and comorbidity have to be considered, whereby a high surgical risk (e.g. high EuroSCORE) choosing an interventional revascularization procedure. Mohr FW, Serruys PW, for the SYNTAX investigators (2009) Presented at ESC 2009.

30 Technical considerations Development of procedural techniques and devices until the trial is finished may have outdated the ones initially used. This may especially apply for PCI, with new stent generations every couple of years, the new generation having proven superiority versus the Taxus stent( less Stent thrombosis, less events).

31 Completeness of revascularization Investigators in SYNTAX too aggressive in PCI, full metal jacket, period of the» DES euphoria» Average stents per patient = 4.6 ± 2.3 with 48% receiving > 5 stents. FAME study - only hemodynamically relevant stenosis should be treated by PCI,by measuring FFR. Number of stenosis to be stented could be reduced by 37% accompanied by a significant reduction in MACE rates. Hong MK et al. Eur Heart J.2006; 27: Tonino PA et al. N Engl J Med.2009; 360:

32 SYNTAX trial: The Reality Difference is driven by the weakest end point - repeated revascularisation. Combined hard events did not demonstrate a difference. Left main disease is no longer a domain of CABG, since DES implantation revealed comparable results.

33 REBUTTAL

34 Scenario before SYNTAX Cardiac Surgeon - Guidelines favor CABG surgery in three-vessel disease. Left Main is the exclusive domain of surgeons Cardiologist - data favoring surgery based on antique studies comparing CABG surgery with PTCA Until now, no statistical difference in hard endpoints that really matter was seen - death and myocardial infarction. PCI is limited by restenosis, surgery is associated with a higher percentage in stroke.

35 Scenario after SYNTAX Interventional Cardiologist: Thinks & Tells SYNTAX questionable primary endpoint definition only driven by TVR. impact of hospital stay, surgical complications, and cognitive decline were excluded PCI or surgery both are options with advantages and problems. With PCI, you may need another stent, but only 1 2 additional days in hospital. With surgery, a good long-term solution but will have a higher risk of stroke and the inconveniencies of major surgery.

36 Scenario after SYNTAX Cardiac Surgeon: Thinks Cardiac surgeon argues that there is still no justified choice between surgery and PCI SYNTAX demonstrates that CABG remains the gold standart for 3V and LM patients End of story? NO!

37 Cardiologists and Surgeons had learned from each others thanks to Syntax Trial Surgery is the first choice for patients with severe threevessel disease and medium or high SYNTAX score. PCI represents a good alternative for patients with three vessel disease and/or left main stenosis in cases where coronary anatomy is suitable for PCI with a reasonable number of stents. Patient has to be understood in all his aspects, not only in the number of coronary stenoses, but also in his wishes, fears, cultural habits and local economy.

38 TAXUS Stent MACCE (%) MACCE per centers CABG vs. TAXUS TAXUS Stent MACCE (%)100 Institut Jacques Cartier (France) CABG MACCE (%)

39 Main clinical implication of SYNTAX SYNTAX was a true landmark study, certainely the best negative trial of the decade The study design can be regarded as a model for daily clinical practice. A meticulous analysis of coronary pathology by surgeon and cardiologist. A careful individual risk assessment and a consensus decision of all, who were involved A Team Approach.

40 Thank you for your attention