PCI for Left Main CAD The Guidelines Should

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

DISCLOSURES Jeffrey J. Popma, MD Grants/Contracted Research – Abbott Vascular, Boston Scientific Corporation, Cordis, a Johnson & Johnson company, Medtronic Cardio. Vascular, 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.

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

The Evidence for CABG over Medical Therapy Non Randomized Comparative Outcomes Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. 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) p 765 -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) p 765 -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) p 765 -77

CABG Not Beneficial in Everyone CABG did not significantly improve survival in: (1) a nonstenotic dominant right or balanced coronary circulation (2) a stenotic dominant Control is required for study validity, to avoid the fallacy right coronary artery of post hoc ergo propter hoc reasoning. and normal LVEF, (3) LM coronary stenosis of 50 to 59 percent and normal or mildly abnormal left ventricular function. Chaitman AJC 1981 48(4) p 765 -77

Not All LM Disease is the Same

Left Main PCI: Guidelines Should Be Changed! § Evidence for CABG over Medical Therapy for Left Main CAD § Appropriateness Guidelines Control is required for study validity, to avoid the fallacy § Syntax and reasoning. of post hoc ergo propter hoc 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 Coronary revascularization is appropriate when the expected benefits in terms of survival and health outcomes Control is required for study validity, to avoid the fallacy (symptoms, of post hoc ergo propter hoc reasoning. 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 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 Control is required for study validity, to avoid the fallacy ofthe indication but with uncertainty meaning that more post hoc ergo propter hoc reasoning. 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 The Appropriateness Guidelines do not provide much room for PCI in patients with left main disease 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

Left Main PCI: Guidelines Should Be Changed! § Evidence for CABG over Medical Therapy for Left Main CAD § Appropriateness Guidelines Control is required for study validity, to avoid the fallacy § Syntax and reasoning. of post hoc ergo propter hoc 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 62 EU Sites + 23 US Sites Heart Team (surgeon & interventionalist) All Pts with de novo 3 VD Amenable for both Amenable for only one treatment options Treatment preference treatment approach (9. 4%) Stratification: Referring MD or pts. refused Stratification: LM consent (7. 0%) informedand Diabetes LM and Diabetes Inclusion/exclusion (4. 7%) Randomized. Withdrew before consent (4. 3%) Arms Two Registry Arms N=1800 N=1275 Other (1. 8%) Randomized Arms * Two Registry Arms Medical treatment (1. 2%) TAXUS CABG PCI CABG n=1800 TAXUS vs 2500 N=903 N=1077 N=897 n=1077 n=897 n=903 750 w/ f/u 71% enrolled no f/u LM vs 3 VD Non. DM 5 yr f/u 3 VD Non DM DM LM DM 66. 3% 28. 5% 33. 7% 71. 5% 65. 4% 28. 2% (N=3, 075) n=428 n=649 34. 6% 71. 8% PCI all N=198 w/ captured n=198 follow up * TAXUS® Express® Stent USVC. TBD. October 2007. Page 16 of 157 Total enrollment and/or LM disease (N=4, 337) N=3075

Adverse Events to 12 Months Left Main Subset All-Death Stent (N=357) CABG (N=348) CVA (Stroke) P=0. 88* P=0. 009* Number Needed to Prevent 4. 4% 4. 2% Number of CABGs needed to prevent one re-PCI = 19 Myocardial Infarction At the cost of 9 times as P=0. 97* many strokes 2. 7% 0. 3% Revascularization P=0. 02* 4, 1% 4. 3% 12. 0% 6. 7%

Two Year Outcome in LM Subgroup CABG TAXUS® Express® Stent P=0. 48 Patients, % Number Needed to Prevent P=0. 01 P=0. 27 This means 14 of every 15 CABGs were unnecessary! Death/CVA/MI Revasc Left Main Disease n=705 Presented at ESC September 2009 by A. Pieter Kappetein MD Ph. D MACCE ITT population 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. 90532967 September 2009 Page 18 of 25 Number of CABGs needed to prevent one re-PCI = 15

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 SYNTAX: Diabetes and Metabolic Syndrome • Banning ACC/i 2 • 28 March 2009 • Slide 19

MACCE to 12 Months by SYNTAX Score Tertile High Scores (33+) Death CVA 4. 1% 3. 4% PCI 9. 7% 0. 8% P- CABG (N=150) TAXUS (N=135) value* 0. 06 0. 22 LM Subset† 50 40 Cumulative Event Rate (%) CABG P=0. 008* 30 MI 6. 0% 7. 6% Death, CVA or 10. 8% MI 14. 1% Revasc. 17. 8% 4. 9% KM Event rate ± 1. 5 SE, *chi 0. 65 0. 40 0. 001 square or Fisher exact test 25. 3% 20 12. 9% 10 0 0 6 12 Months Since Allocation †Patients with isolated LM or LM +1, +2 or +3 vessel disease Site-reported Data; ITT population

Left Main PCI: Guidelines Should Be Changed! § Evidence for CABG over Medical Therapy for Left Main CAD § Appropriateness Guidelines Control is required for study validity, to avoid the fallacy § Syntax and reasoning. of post hoc ergo propter hoc 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

CABG PCI n n Summary 95% CI OR Year 1 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

CABG n PCI n 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

CABG n PCI n 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

Left Main PCI: Guidelines Should Be Changed! § Evidence for CABG over Medical Therapy for Left Main CAD § Appropriateness Guidelines Control is required for study validity, to avoid the fallacy § Syntax and reasoning. of post hoc ergo propter hoc 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

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

Current Evidence Justifies Left Main PCI as a Class IIa Recommendation ----- with qualifications • 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? Control is required for study validity, to avoid the fallacy • hoc ergo propter hoc reasoning. of post 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