1. Columbia University Medical Center Cardiovascular Research Foundation New York City, NY Akiko Maehara, MD Use of IVUS Reduces Stent Thrombosis and Myocardial Infarction Results from the Prospective, Multicenter ADAPT-DES Study

2. ADAPT-DES Study Design Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents Up to 11,000 pts prospectively enrolled No clinical or anatomic exclusion criteria 11 sites in US and Germany Clinical FU at 30 days, 1 year and 2 years Angio core lab assessment all STs w/1:2 matching controls Assess platelet function after adequate DAPT loading and GPI washout: Accumetrics VerifyNow Aspirin, VerifyNow P2Y12, and VerifyNow IIb/IIIa assays (results blinded) PCI with ≥1 non-investigational DES Successful and uncomplicated (IVUS/VH substudy; Up to 3000 pts enrolled) clinicaltrials.gov NCT00638794

3. ADAPT-DES - Current Cohort - Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents 8,583 pts prospectively enrolled No clinical or anatomic exclusion criteria 11 sites in US and Germany Clinical FU at 30 days, 1 year PCI with ≥1 non-investigational DES Successful and uncomplicated clinicaltrials.gov NCT00638794 IVUS Use: 3349 pts No IVUS: 5234 pts

4. IVUS Use n = 3349 No IVUS n = 5234 P Value Age (yr) 62.9±10.864.1±10.9<0.0001 Male 73.4%74.5%0.23 Diabetes 31.3%33.1%0.073 Hypertension 78.1%80.6%0.0055 Hyperlipidemia 68.3%78.2%<0.0001 Current smoking 25.4%20.8%<0.0001 Prior MI 24.6%25.6%0.30 Prior CABG 12.7%19.9%<0.0001 STEMI presentation 12.6%7.5%<0.0001 Patient Characteristics

5. IVUS Use n = 3349 No IVUS n = 5234 P Value # of lesions treated 1.48±0.751.52±0.81<0.0001 Bifurcation lesion 14.1%16.1%0.012 In-stent restenosis lesion 11.3%9.7%0.020 Bypass graft lesion 3.0%6.3%<0.0001 # of stents implanted 1.73±0.971.71±1.050.63 Total stent length (mm) 33.6±21.931.7±22.60.0002 Max device diameter (mm) 3.44±0.563.15±0.50<0.0001 Max balloon pressure (atm) 16.9±3.716.7±3.50.13 Lesion and Procedural Characteristics

6. How IVUS changed the procedure? Guide and Optimize Procedure (74%) No change (26%) Larger Size of Stent/Balloon Higher Pressure Longer Stent Post Dilation Under- expansion Mal-apposition Additional Stent (%)

7. How IVUS was used? Pre&Post PCI (63%) Post PCI only (30%) Pre PCI only (7%) Pre IVUS done Only Post IVUS done 8.9 7.6 6.3 5.8 6.5 6.1 Shown as mean value, All p<0.0001 N=2364 lesions (mm 2 )

8. IVUS Use n = 3349 No IVUS n = 5234 P Value Definite/probable ST 0.52% (17)1.04% (53)0.011 - Acute<1day 0.06% (2)0.04% (2)0.66 - Subacute (1-30day) 0.27% (9)0.56% (29)0.051 - Late (>30day to 1yr) 0.25% (8)0.46% (23)0.12 All death 1.79% (58)2.04% (103)0.40 Cardiac death 0.84% (27)1.19% (60)0.12 All MI 2.46% (81) 3.68% (188) 0.0022 - Peri-procedural MI 1.26% (42)1.53% (80)0.29 - ST related MI 0.37% (12)0.59% (30)0.16 - Non ST related MI 0.87% (28)1.58% (79)0.0054 Ischemic driven TVR* 2.42% (81)3.95% (207)0.0001 Clinical Outcome at 1 year * Site reported

9. Relationship between IVUS Use and Definite/Probable Stent Thrombosis within 1 year Definite/Probable ST (%) 2 Time in Months 33493251322131973023 52345015497849384585 Number at risk: IVUS Use No IVUS Use P = 0.01 HR: 0.50 [95% CI: 0.29, 0.86] IVUS Use No IVUS Use

10. HR [95%CI]P value IVUS use 0.35 [0.19, 0.66]0.0012 On DAPT till stent thrombosis 0.27 [0.14, 0.53]0.0001 Max device diameter (mm) 0.59 [0.35, 1.00]0.052 STEMI presentation 2.93 [1.60, 5.35]0.0005 PRU>208 2.37 [1.42, 3.95]0.0009 Diabetes 1.63 [1.00, 2.67]0.050 Total stent length (mm) 1.01 [1.00, 1.02]0.025 Mutivariable Cox PHR Models of 1-year Stent Thrombosis Number events=68, Total at risk=8401 Other non significant covariates entered to the model: ARU≥550

11. Relationship between IVUS Use and MI within 1 year MI (%) 0 1 2 3 4 5 Time in Months 036912 33493209317131412969 52344932488248304460 Number at risk: IVUS Use No IVUS Use P = 0.002 HR: 0.67 [95% CI: 0.51, 0.87] 2.5% 3.7% IVUS Use No IVUS Use

12. HR [95%CI]P value IVUS use 0.65 [0.49, 0.87]0.0034 Cr Clearance <60 ml/min 1.64 [1.19, 2.27]0.0025 Three vessel CAD 1.57 [1.22, 2.02]0.0005 Diabetes 1.48 [1.15, 1.89]0.0021 Acute coronary syndrome 1.41 [1.10, 1.80]0.0064 Prior MI 1.35 [1.04, 1.75]0.023 Mutivariable Cox PHR Models of 1-year MI Number events=269, Total at risk=8547 Other non significant covariates entered to the model: Male, Hemoglobin (g/dL)

13. Relationship between IVUS Use and MI not related to ST within 1 year Non-ST related MI (%) 2 3 Time in Months 33493253321631883015 52345024497449254555 Number at risk: IVUS Use No IVUS Use HR: 0.55 [95% CI: 0.36, 0.84] P = 0.005 IVUS Use No IVUS Use

14. Cause of MI not related to ST within 1 year In-stent restenosis with MI onset New MI Other No angiography done Culprit unclear by angiography 1/3=culprit vessel 2/3=non culprit vessel IVUS may reduce

15. Impact of Complexity of Procedure One vessel treatment ≥2 vessel or left main or bifurcation treated

16. ADAPT-DES - Current Cohort - Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents 8,583 pts prospectively enrolled No clinical or anatomic exclusion criteria 11 sites in US and Germany Clinical FU at 30 days, 1 year PCI with ≥1 non-investigational DES Successful and uncomplicated clinicaltrials.gov NCT00638794 IVUS Use: 3349 pts No IVUS: 5234 pts IVUS Substudy: 2670 pts

17. Stent Thrombosis n = 10 No Stent Thrombosis n = 2060 P Value Reference lumen CSA (mm 2 ) 8.4 [7.0, 9.8]8.1 [6.2, 10.6]0.78 Minimum Lumen CSA (mm 2 ) 5.4 [4.4, 7.5]5.8 [4.5, 7.6]0.82 - MLA<5mm 2 40% (4)33.7% (821)0.74 - MLA<4mm 2 20% (2)15.4% (375)0.66 Stent expansion* (%) 69.9 [58.2, 86.7]73.1 [62.1, 84.5]0.68 Plaque burden at MLA (%) 57.4 [52.7, 59.3]56.0 [49.5, 62.2]0.62 Plaque burden at prox ref (%) 63.6 [46.6, 71.0] 48.7 [40.4, 57.1] 0.022 IVUS Planar Analysis * Stent Expansion=Minimum Stent CSA/Reference lumen CSA

18. IVUS use resulted in longer stent length and larger stent size without increasing peri-procedural MI. IVUS use resulted in longer stent length and larger stent size without increasing peri-procedural MI. These data, drawn from the largest prospective registry of IVUS use to date, suggest that appropriate IVUS guidance during DES PCI may result in less stent thrombosis as well as fewer myocardial infarctions. These data, drawn from the largest prospective registry of IVUS use to date, suggest that appropriate IVUS guidance during DES PCI may result in less stent thrombosis as well as fewer myocardial infarctions. ADAPT-DES: Conclusions and Implications