The Guidelines Should Be Change! PCI for Left Main CAD: The Guidelines Should Be Change! Jeffrey J. Popma, MD Director, Innovations in Interventional Cardiology Senior Attending Physician Beth Israel Deaconess Medical Center Associate Professor of Medicine Harvard Medical School Boston, MA

Jeffrey J. Popma, MD DISCLOSURES Grants/Contracted Research Honoraria Abbott Vascular, Boston Scientific Corporation, Cordis, a Johnson & Johnson company, Medtronic CardioVascular, Inc. Honoraria Abbott Vascular, Boston Scientific Corporation, Cordis, a Johnson & Johnson company I intend to reference unlabeled/unapproved uses of drugs or devices in my presentation. I intend to reference transcatheter aortic valves.

Guidelines Should Be Changed! Left Main PCI: Guidelines Should Be Changed! Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Evidence for CABG over Medical Therapy for Left Main CAD Appropriateness Guidelines Syntax and Other RCT Assessing Outcomes and CE 2009 ACC-AHA Guidelines Update Perspectives

The Evidence for CABG over Medical Therapy Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Non Randomized Comparative Outcomes Not Superior In All Subset CAAS contains a registry of 24,179 patients who underwent coronary angiography between August 1974 and June 1979 at 15 medical centers. 1,492 registry patients with left main coronary artery disease (> 50 percent) Chaitman AJC 1981 48(4) p765-77

Survival is Improved over Med Rx Alone Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Chaitman AJC 1981 48(4) p765-77

The Benefit is Related to the LM Severity Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Chaitman AJC 1981 48(4) p765-77

CABG Not Beneficial in Everyone Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. CABG did not significantly improve survival in: a nonstenotic dominant right or balanced coronary circulation a stenotic dominant right coronary artery and normal LVEF, LM coronary stenosis of 50 to 59 percent and normal or mildly abnormal left ventricular function. Chaitman AJC 1981 48(4) p765-77

Not All LM Disease is the Same

Guidelines Should Be Changed! Left Main PCI: Guidelines Should Be Changed! Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Evidence for CABG over Medical Therapy for Left Main CAD Appropriateness Guidelines Syntax and Other RCT Assessing Outcomes and CE 2009 ACC-AHA Guidelines Update Perspectives

“Appropriateness” Criteria Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Patel et al JACC 2009 53 (February): 530-553

Definition Used for Analysis Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Coronary revascularization is appropriate when the expected benefits in terms of survival and health outcomes (symptoms, functional status, and/or quality of life) exceed the expected negative consequences of the procedure Patel et al JACC 2009 53 (February): 530-553

Appropriateness Rankings Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Appropriate: Score 7-9. Coronary revascularization is generally accepted and is a reasonable approach for the indication and is likely to improve the patient’s health outcome or survival Uncertain: Score 4-6. Coronary revascularization may be acceptable and may be a reasonable approach for the indication but with uncertainty meaning that more research and/or patient information is needed to further classify the indication Inappropriate Score: 1-3. Coronary revascularization is not generally accepted and is not a reasonable approach for the indication and is unlikely to improve the patient’s health outcome or survival Patel et al JACC 2009 53 (February): 530-553

Appropriateness: PCI v CABG Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. The Appropriateness Guidelines do not provide much room for PCI in patients with left main disease Patel et al JACC 2009 53 (February): 530-553

Guidelines Should Be Changed! Left Main PCI: Guidelines Should Be Changed! Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Evidence for CABG over Medical Therapy for Left Main CAD Appropriateness Guidelines Syntax and Other RCTs Assessing Outcomes and CE 2009 ACC-AHA Guidelines Update Perspectives

Strong Conclusions for CABG Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning.

SYNTAX Trial Design + TAXUS n=903 PCI n=198 CABG n=1077 n=897 N=198 62 EU Sites + 23 US Sites TAXUS n=903 PCI n=198 CABG n=1077 n=897 no f/u n=428 5yr f/u n=649 all captured w/ follow up 2500 750 w/ f/u vs Total enrollment N=3075 Stratification: LM and Diabetes Two Registry Arms Randomized Arms n=1800 N=1275 N=1800 Heart Team (surgeon & interventionalist) N=198 N=1077 Amenable for only one treatment approach TAXUS* N=903 N=897 Amenable for both treatment options LM 33.7% 3VD 66.3% 34.6% 65.4% 71% enrolled (N=3,075) All Pts with de novo 3VD and/or LM disease (N=4,337) Treatment preference (9.4%) Referring MD or pts. refused informed consent (7.0%) Inclusion/exclusion (4.7%) Withdrew before consent (4.3%) Other (1.8%) Medical treatment (1.2%) USVC.TBD.October 2007.Page 16 of 157 DM 28.5% Non DM 71.5% NonDM 71.8% 28.2% *TAXUS® Express® Stent 16 16

Adverse Events to 12 Months Left Main Subset Stent (N=357) CABG (N=348) All-Death CVA (Stroke) P=0.88* P=0.009* Number Needed to Prevent 4.4% 2.7% Number of CABGs needed to prevent one re-PCI = 19 4.2% 0.3% Myocardial Infarction Revascularization At the cost of 9 times as many strokes P=0.97* P=0.02* 12.0% 4,1% 6.7% 4.3% 17

Presented at ESC September 2009 by A. Pieter Kappetein MD PhD Two Year Outcome in LM Subgroup TAXUS® Express® Stent CABG P=0.01 P=0.48 P=0.27 Number Needed to Prevent Number of CABGs needed to prevent one re-PCI = 15 Patients, % This means 14 of every 15 CABGs were unnecessary! 2-Year_Randomized_Draft_dryrun2.doc Exhibits 18 & 20 Death/CVA/MI Revasc MACCE Left Main Disease n=705 ITT population Presented at ESC September 2009 by A. Pieter Kappetein MD PhD The safety and effectiveness of the TAXUS® Stent Systems have not been established in the following patient populations: lesions located in the unprotected left main coronary artery, or patients with multi-vessel disease. 18

SYNTAX Score A prospective angiographic tool to grade the complexity of coronary artery disease Goal: Obtain evidence-based guidelines for selecting revascularization technique (surgery or PCI) The SYNTAX Score will be retroactively weighted based on MACCE at 1 and 5 years to optimize its prognostic value 19

MACCE to 12 Months by SYNTAX Score Tertile High Scores (33+) CABG PCI P-value* Death 4.1% 9.7% 0.06 CVA 3.4% 0.8% 0.22 MI 6.0% 7.6% 0.65 Death, CVA or MI 10.8% 14.1% 0.40 Revasc. 4.9% 17.8% 0.001 TAXUS (N=135) CABG (N=150) LM Subset† 40 50 20 30 10 P=0.008* 25.3% Cumulative Event Rate (%) 12.9% 6 12 Months Since Allocation †Patients with isolated LM or LM +1, +2 or +3 vessel disease KM Event rate ± 1.5 SE, *chi square or Fisher exact test Site-reported Data; ITT population 20 20

Guidelines Should Be Changed! Left Main PCI: Guidelines Should Be Changed! Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Evidence for CABG over Medical Therapy for Left Main CAD Appropriateness Guidelines Syntax and Other RCT Assessing Outcomes and CE 2009 ACC-AHA Guidelines Update Perspectives

Left Main White Paper Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Kandzari et al JACC 2009 54:1576–88

No Difference In Mortality Up To 3 Years CABG n PCI Summary OR 95% CI 1932 1393 1.00 0.70-1.41 Year 2 890 528 1.27 0.83-1.94 Year 3 578 263 1.11 0.66-1.86 No Difference In Mortality Up To 3 Years

No Difference In Death, MI and Stroke Up To 3 Years CABG n PCI Summary OR 95% CI Year 1 1614 1239 0.84 0.57-1.22 Year 2 652 432 1.25 0.81-1.94 Year 3 451 236 1.16 0.68-1.98 No Difference In Death, MI and Stroke Up To 3 Years

Increased TVR Up To 3 years CABG n PCI Summary OR 95% CI Year 1 1692 1240 4.36 2.60-7.32 Year 2 699 417 4.20 2.21-7.97 Year 3 447 211 3.30 0.96-11.33 Increased TVR Up To 3 years

Guidelines Should Be Changed! Left Main PCI: Guidelines Should Be Changed! Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Evidence for CABG over Medical Therapy for Left Main CAD Appropriateness Guidelines Syntax and Other RCT Assessing Outcomes and CE 2009 ACC-AHA Guidelines Update Perspectives

2009 ACC-AHA PCI Updates J. Am. Coll. Cardiol. 2009;54;2205-2241 Kushner FG JACC 2009;54;2205-2241

Guidelines Should Be Changed! Left Main PCI: Guidelines Should Be Changed! Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Evidence for CABG over Medical Therapy for Left Main CAD Appropriateness Guidelines Syntax and Other RCT Assessing Outcomes and CE 2009 ACC-AHA Guidelines Update Perspectives

Current Evidence Justifies Left Main PCI as a Class IIa Recommendation ----- with qualifications Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Is the syntax score high? Is it a simple ostial or mid-shaft lesion? Can we achieve complete revascularization? Is revascularization of an occluded RCA important? Is the left main heavily calcified? Is the left main small, and/or tortuous? Is the patient an insulin dependent diabetic? Do co-morbid consisderations make the patient a poor candidate for CABG? Teirstein PS SCRIPPS 2009 31