1. Ten-Year Follow-up Survival of the Medicine, Angioplasty, or Surgery Study (MASS-II): a Randomized Controlled Clinical Trial of Therapeutic Strategies for Multivessel Coronary Artery Disease Whady Hueb, Neuza Lopes, Bernard J. Gersh, Paulo R. Soares, Expedito E. Ribeiro, Alexandre C. Pereira, Desiderio Favarato, Antonio Sérgio C. Rocha, Alexandre C. Hueb and Jose A.F. Ramires Heart Institute (InCor), University of Sao Paulo, Sao Paulo, Brazil

2. Competing Interests The authors declare no potential competing interest.

3. Compared to CABG treatment, PCI or MT is associated with higher rates of angina and subsequent revascularization, but no significant differences in mortality or rates of MI have been found. Revascularization therapy in stable multivessel coronary artery disease (CAD) and preserved ventricular function remains controversial. BACKGROUND

4. To our Knowledge, there is no study that has ever compared end points among these 3 therapeutic strategies for more than a 5-year follow-up period. BACKGROUND

5. To compare 10-year follow-up survival of the medical treatment, angioplasty, or surgical strategies among patients with stable multivessel CAD and preserved ventricular function. OBJECTIVE

6. METHODSRANDOMIZATION ANGIOPLASTY(BMS) MEDICAL TREATMENT (alone) SURGERY (on-pump CABG) Stable Angina Multivessel Coronary Artery Disease Preserved Left Ventricular Function Surgeon / Interv. Cardiologist / Clinical Cardiologist Team approval Recruitment: May 1995 - May 2000 (Heart Institute - InCor) Hueb W., et al. Circulation 2007;115:1082-1089

7. METHODS Primary end-point (composite): ✓ overall mortality, ✓ myocardial infarction, ✓ refractory angina requiring new revascularization Ten-Year Follow-Up

8. All analysis were done according to intention to treat principle. Sample size: power 80% and a two-side level of significance of 0.05% - 191 patients in each group. Statistical test: Chi-Square, log-rank test, ANOVA, Tukey multiple-comparisons test, Cox’s regression and McNemar test. Statistical Analysis

9. RESULTS Hueb W, et al. J Am Coll CardioI 2004; 43:1743-51 1465 patients non-randomized: Surgery(n=203) Medical Treatment (n=203) Angioplasty (n=205) excluded 18.692 patients: coronary <30% lesion - 5192 single coronary disease - 3531 previous CABG/PCI - 2908 valvar disease 2701 other - 4361 refused to participate in this trial or refused the surgical procedure Database: 20.769 coronary angiographies Elegible: 2.076 patients (suitable to PCI-CABG) MASS II Randomized: 611 patients

10. Demographic Profile Male, (%) Age (years) mean±SD Medical History Previous MI, (%) Smoker, (%) Hypertension, (%) Diabetes mellitus, (%) CCS class 2 or 3, (%) 6960±93933553678 MT (n = 203) MT (n = 203) 72 61±8 4132632985 CABG (n = 203) CABG (n = 203) 6760±45227602676 PCI (n=205) PCI (n=205) Characteristic 0.4120.9590.0240.0130.2150.0620.006 P P Baseline Characteristics of MASS II

11. Clinical Characteristics - Metabolic Aspects - MT PCI CABG (n=203) (n=205) (n=203) Total Cholesterol (mg/l) 222±39 220±41 214±42 0.063 LDLChol (mg/dl) 148±34 147±36 143±36 0.305 HDL Chol (mg/dl) 37±10 38±10 37±10 0.870 Triglicerides (mg/dl) 178±82 181±73 169±84 0.235 Glucose mg/dl) 139±68 128±60 122±44 0.062 P P

12. Double-Vessel Disease, (%) Triple-Vesel Disease, (%) Proximal LAD disease, (%) Mean ejection fraction (mean±DP) Double-Vessel Disease, (%) Triple-Vesel Disease, (%) Proximal LAD disease, (%) Mean ejection fraction (mean±DP) MT (n = 203) MT (n = 203) CABG (n = 203) CABG (n = 203) PCI (n = 205) PCI (n = 205) 41 59 89 0.68±0.07 41 59 89 0.68±0.07 42 58 93 0.67±0.09 42 58 93 0.67±0.09 42 58 93 0.67±0.08 42 58 93 0.67±0.08 P P Baseline Characteristics - Angiographic Profile - 0.980 0.312 0.984 0.980 0.312 0.984

13. Major Adverse Cardiac Events - 10-Year Follow-Up - Outcomes Primary Endpoints, (%) Overall Mortality, (%) Myocardial Infarction, (%) Aditional Intervention, (%) Outcomes Primary Endpoints, (%) Overall Mortality, (%) Myocardial Infarction, (%) Aditional Intervention, (%) MT (n = 203) MT (n = 203) CABG (n = 203) CABG (n = 203) PCI (n = 205) PCI (n = 205) 59.1 31 20.7 39.4 59.1 31 20.7 39.4 33 25.1 10.3 7.4 33 25.1 10.3 7.4 42.4 24.1 13.3 41.9 42.4 24.1 13.3 41.9 P P 0.089 <0.001 0.010 0.001

14. Treatment Group InitialInitial 6 Year 3 Year 205 205203203 203203164168159164168159189184179189184179 10 Year 156152140156152140 PCICABGMTPCICABGMT Overall Mortality-Free Survival

15. Treatment Group InitialInitial 6 Year 3 Year 203 203205203 205203155130121155130121175147140175147140 10 Year 1501089315010893CABGPCIMTCABGPCIMT Ten-Year Follow-up Event-free Survival

16. End Point and Treatment Allocation - CABG vs MT -

17. End Point and Treatment Allocation - CABG vs PCI -

18. End Point and Treatment Allocation - PCI vs MT -

19. Multivariate Analysis for Treatment Allocation Primary end points TreatmentPCI/CABGMT/CABG TreatmentPCI/CABGMT/CABG 1.462.29 1.06-2.021.69-3.101.06-2.021.69-3.10 MultivariateHRMultivariateHR <0.0010.021<0.001<0.0010.021<0.001 Variables pp 95% CI Overall Death TreatmentPCI/CABGMT/CABG TreatmentPCI/CABGMT/CABG 0.971.290.971.290.65-1.440.89-1.870.65-1.440.89-1.870.2410.8780.1750.2410.8780.175

20. Multivariate Analysis for Treatment Allocation Myocardial Infarction Treatment PCI/CABG MT/CABG Myocardial Infarction Treatment PCI/CABG MT/CABG 2.90 2.69 2.90 2.69 1.39-6.01 1.30-5.60 1.39-6.01 1.30-5.60 Multivariate HR Multivariate HR 0.012 0.004 0.008 0.012 0.004 0.008 Variables p p 95% CI Additional Intervention Treatment PCI/CABG MT/CABG Additional Intervention Treatment PCI/CABG MT/CABG 3.71 7.58 3.71 7.58 1.82-7.52 3.88-14.81 1.82-7.52 3.88-14.81 <0.001

21. CONCLUSION All three therapeutic regimens yielded similar and relatively low rates of overall mortality. Compared with CABG, angioplasty was associated with elevated rate of myocardial infarction and need for revascularization. Medical therapy showed significant incidence of myocardial infarction and high rate of additional revascularization.