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

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 NCT

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 NCT IVUS Use: 3349 pts No IVUS: 5234 pts

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

IVUS Use n = 3349 No IVUS n = 5234 P Value # of lesions treated 1.48± ±0.81< 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%< # of stents implanted 1.73± ± Total stent length (mm) 33.6± ± Max device diameter (mm) 3.44± ±0.50< Max balloon pressure (atm) 16.9± ± Lesion and Procedural Characteristics

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 (%)

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

IVUS Use n = 3349 No IVUS n = 5234 P Value Definite/probable ST 0.52% (17)1.04% (53) Acute<1day 0.06% (2)0.04% (2) Subacute (1-30day) 0.27% (9)0.56% (29) 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) Peri-procedural MI 1.26% (42)1.53% (80) ST related MI 0.37% (12)0.59% (30) Non ST related MI 0.87% (28)1.58% (79) Ischemic driven TVR* 2.42% (81)3.95% (207) Clinical Outcome at 1 year * Site reported

Relationship between IVUS Use and Definite/Probable Stent Thrombosis within 1 year Definite/Probable ST (%) 2 Time in Months 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

HR [95%CI]P value IVUS use 0.35 [0.19, 0.66] On DAPT till stent thrombosis 0.27 [0.14, 0.53] Max device diameter (mm) 0.59 [0.35, 1.00]0.052 STEMI presentation 2.93 [1.60, 5.35] PRU> [1.42, 3.95] 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

Relationship between IVUS Use and MI within 1 year MI (%) Time in Months Number at risk: IVUS Use No IVUS Use P = HR: 0.67 [95% CI: 0.51, 0.87] 2.5% 3.7% IVUS Use No IVUS Use

HR [95%CI]P value IVUS use 0.65 [0.49, 0.87] Cr Clearance <60 ml/min 1.64 [1.19, 2.27] Three vessel CAD 1.57 [1.22, 2.02] Diabetes 1.48 [1.15, 1.89] Acute coronary syndrome 1.41 [1.10, 1.80] 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)

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

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

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

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 NCT IVUS Use: 3349 pts No IVUS: 5234 pts IVUS Substudy: 2670 pts

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] MLA<5mm 2 40% (4)33.7% (821) 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] IVUS Planar Analysis * Stent Expansion=Minimum Stent CSA/Reference lumen CSA

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