Show me the Data: Key Clinical Trials of 2016 Ehtisham Mahmud, MD, FACC, FSCAI Professor and Division Chief, Cardiovascular Medicine Director,

Transcription

1 Show me the Data: Key Clinical Trials of 2016 Ehtisham Mahmud, MD, FACC, FSCAI Professor and Division Chief, Cardiovascular Medicine Director, Sulpizio Cardiovascular Center-Medicine University of California San Diego

2 Disclosures Clinical trial support: Boston Scientific, Corindus, Medinol Consulting: St Jude, Corindus, Medtronic Equity/Stock Options: Abiomed, Ra Medical Speakers Bureau: Medtronic, Abbott Vascular

3 Key Clinical Trials In Interventional Cardiology: 2016 Left Main Dis eas e (PCI vs CABG): EXCEL, NOBLE Structural Heart Dis eas e: PARTNER 2A, RESPECT Acute Myoca rdial Infarction: DANAMI-3 DEFER, DANAMI-3 POST New Devices /Technology: BIONICS, LEADERS FREE, CORA PCI BVS: ABSORB II, ABSORB CHINA

4 LEFT MAIN DISEASE: PCI VS CABG

5 Left Main Disease CABG superior to medical therapy for mortality reduction In SYNTAX, limited number of left main patients enrolled In contemporary medicine, is a DES approach comparable to CABG EXCEL NOBLE Relevant endpoints: Death, MI, Stroke,?repeat revascularization

6 EXCEL: Study Des ign R

7 Site Reported SYNTAX Score Low ( 22) Intermediate (23-32) High ( 33) Core Lab 59.2% 40.8% PCI 32.2% 42.8% 25.1% Mean 20.6 ± 6.2 Mean 26.9 ± 8.8 P = % 38.2% CABG 39.3% 37.3% P = % Mean 20.5 ± 6.1 Mean 26.0 ± 9.8

8 Primary Endpoint Death, Stroke or MI at 3 Years Death, s troke or MI (%) No. at Risk: PCI CABG 25% 20% 15% 10% 5% 0% CABG (n=957) PCI (n=948) HR [95%CI] = 1.00 [95% CI: 0.79, 1.26] P = 0.98 Months % 14.7%

9 Primary and Hierarchical Secondary Clinical Outcomes PCI (n =948) CABG (n =957) Diff [upper confidence limit] P NI HR [95%CI] P Sup Primary endpoint Death, stroke or MI at 3 years 15.4% 14.7% 0.7% [4.0%] Secondary endpoints Death, stroke or MI at 30 days Death, stroke, MI or ischemia-driven revasc at 3 years Death, stroke or MI at 3 years 4.9% 7.9% -3.1% [-1.2%] < % 19.1% 4.0% [7.2%] % 14.7% [0.79, 1.26] 0.98 Stone et al; NEJM 2016 The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years, 2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven revascularization at 3 years. Upper 97.5% confidence limit; Upper 95.0% confidence limit.

10 Primary and Hierarchical Secondary Clinical Outcomes PCI (n =948) CABG (n =957) Diff [upper confidence limit] P NI HR [95%CI] P Sup Primary endpoint Death, stroke or MI at 3 years 15.4% 14.7% 0.7% [4.0%] Secondary endpoints Death, stroke or MI at 30 days Death, stroke, MI or ischemia-driven revasc at 3 years Death, stroke or MI at 3 years 4.9% 7.9% -3.1% [-1.2%] < % 19.1% 4.0% [7.2%] % 14.7% [0.79, 1.26] 0.98 The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years, 2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven revascularization at 3 years. Upper 97.5% confidence limit; Upper 95.0% confidence limit.

11 Primary and Hierarchical Secondary Clinical Outcomes PCI (n =948) CABG (n =957) Diff [upper confidence limit] P NI HR [95%CI] P Sup Primary endpoint Death, stroke or MI at 3 years 15.4% 14.7% 0.7% [4.0%] Secondary endpoints Death, stroke or MI at 30 days Death, stroke, MI or ischemia-driven revasc at 3 years Death, stroke or MI at 3 years 4.9% 7.9% -3.1% [-1.2%] < % 19.1% 4.0% [7.2%] % 14.7% [0.79, 1.26] 0.98 The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years, 2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven revascularization at 3 years. Upper 97.5% confidence limit; Upper 95.0% confidence limit.

12 Primary and Hierarchical Secondary Clinical Outcomes PCI (n =948) CABG (n =957) Diff [upper confidence limit] P NI HR [95%CI] P Sup Primary endpoint Death, stroke or MI at 3 years 15.4% 14.7% 0.7% [4.0%] Secondary endpoints Death, stroke or MI at 30 days Death, stroke, MI or ischemia-driven revasc at 3 years Death, stroke or MI at 3 years 4.9% 7.9% -3.1% [-1.2%] < % 19.1% 4.0% [7.2%] % 14.7% [0.79, 1.26] 0.98 The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years, 2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven revascularization at 3 years. Upper 97.5% confidence limit; Upper 95.0% confidence limit.

13 Primary and Hierarchical Secondary Clinical Outcomes PCI (n =948) CABG (n =957) Diff [upper confidence limit] P NI HR [95%CI] P Sup Primary endpoint Death, stroke or MI at 3 years 15.4% 14.7% 0.7% [4.0%] Secondary endpoints Death, stroke or MI at 30 days Death, stroke, MI or ischemia-driven revasc at 3 years Death, stroke or MI at 3 years 4.9% 7.9% -3.1% [-1.2%] < % 19.1% 4.0% [7.2%] % 14.7% [0.79, 1.26] 0.98 The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years, 2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven revascularization at 3 years. Upper 97.5% confidence limit; Upper 95.0% confidence limit.

14 Adjudicated Outcomes at 3 Years (i) PCI (n =948) CABG (n =957) HR [95%CI] P-value Death, stroke or MI (1 e n d p o i) n t 15.4% 14.7% 1.00 [0.79, 1.26] Death 8.2% 5.9% 1.34 [0.94, 1.91] Definite cardiovascular 3.7% 3.4% 1.10 [0.67, 1.80] Definite non-cardiovascular 3.9% 2.3% 1.60 [0.91, 2.80] Undetermined cause 0.8% 0.3% 2.00 [0.50, 7.98] Stroke 2.3% 2.9% 0.77 [0.43, 1.37] MI 8.0% 8.3% 0.93 [0.67, 1.28] Peri-procedural 3.8% 6.0% 0.63 [0.42, 0.96] Spontaneous 4.3% 2.7% 1.60 [0.95, 2.70] STEMI 1.3% 2.8% 0.46 [0.23, 0.91] Non-STEMI 7.0% 5.9% 1.15 [0.80, 1.65] 0.46

15 Adjudicated Outcomes at 3 Years (ii) PCI (n =948) CABG (n =957) HR [95%CI] P-value Death, stroke, MI or IDR 23.1% 19.1% 1.18 [0.97, 1.45] Ischemia-driven revasc (IDR) 12.6% 7.5% 1.72 [1.27, 2.33] < PCI 10.3% 6.8% 1.57 [1.13, 2.18] CABG 3.5% 0.8% 4.29 [1.88, 9.77] <0.001 All revascularization 12.9% 7.6% 1.72 [1.27, 2.33] <0.001 Stent thrombosis, def/prob 1.3% 0.0% - < Definite 0.7% 0.0% Probable 0.7% 0.0% Early (0-30 days) 0.7% 0.0% Late (30 days 1 year) 0.1% 0.0% Very late (1 year - 3 years) 0.5% 0.0% Graft occlusion, symptomatic 0.0% 5.4% - <0.001 Definite stent thrombosis or symptomatic graft occlusion 0.7% 5.4% 0.12 [0.05, 0.28] <0.001

16 Adjudicated Outcomes at 3 Years (ii) PCI (n =948) CABG (n =957) HR [95%CI] P-value Death, stroke, MI or IDR 23.1% 19.1% 1.18 [0.97, 1.45] Ischemia-driven revasc (IDR) 12.6% 7.5% 1.72 [1.27, 2.33] < PCI 10.3% 6.8% 1.57 [1.13, 2.18] CABG 3.5% 0.8% 4.29 [1.88, 9.77] <0.001 All revascularization 12.9% 7.6% 1.72 [1.27, 2.33] <0.001 Stent thrombosis, def/prob 1.3% 0.0% - < Definite 0.7% 0.0% Probable 0.7% 0.0% Early (0-30 days) 0.7% 0.0% Late (30 days 1 year) 0.1% 0.0% Very late (1 year - 3 years) 0.5% 0.0% Graft occlusion, symptomatic 0.0% 5.4% - <0.001 Definite stent thrombosis or symptomatic graft occlusion 0.7% 5.4% 0.12 [0.05, 0.28] <0.001

17 Randomized (n= 1201) Allocated to PCI (n=598) Received PCI (n=585) Did not receive PCI (n=13) Died before PCI (n=1) Patient declined PCI (n=4) PCI operator declined (n=4) LMCA lesion not significant (n=4) Lost to follow-up(n=6) Emigration(n=1) Contact lost (n=2) Withdrawal (n=3) Patients allocated t o PCI (Biolimus DES) in analysis (n=592) 580 received PCI 7 received CABG Allocated to CABG(n=603) Received CABG(n=570 ) Did not receive CABG(n=33) Died before CABG(n=1) Patient declined CABG(n=15) Not eligible for CABG(n=15) Crossover by mistake(n=2) Lost to follow-up(n=11) Emigration(n=0) Contact lost (n=0) Withdrawal (n=11) Patients allocated to CABGin analysis (n=592) 567 received CABG 23 received PCI Christiansen et al; Lancet 2016

18 Primary endpoint: MACCE(Death, MI, Stroke and Repeat Revascularization) HR1 48 ( ); p= % 19 1% PCI did not show non-inferiorit y and CABGwassuperior to PCI Christiansen et al; Lancet 2016

19 All-cause mortality HR1 07( ); p= % 11 6% 9 5% 9.5%

20 Non-procedural myocardial infarction HR2 88 ( ); p= % 1 9%

21 Stroke HR2 25 ( ); p= % 1 7%

22 Total repeat revascularization HR1 50 ( ); p= % 10 4%

23 Kaplan-Meier 5 year estimates by intention-to-treat K-M estimates 4.9% 1.9%

24 Kaplan-Meier 5 year estimates by intention-to-treat K-M estimates 4.9% 1.9%

25 Left Main PCI vs CABG Trials (EXCEL and NOBLE): Implications No difference in mortality or stroke at 3-5 year follow-up Higher risk of nonprocedural myocardial infarction in NOBLE but not EXCEL Higher risk of repeat revascularization with PCI in both trials Longer term follow-up required to evaluate mortality differences For selected patients (SYNTAX 32), left main PCI is an appropriate option although associated with higher revascularization rates

26 Structural Heart Dis eas e

27 Structural Heart Disease TAVR is preferable for high-risk and inoperable patients with aortic stenosis Is TAVR an option for intermediate risk SAVR patients (STS 4)? PARTNER 2A No clear benefit of PFO closure after cryptogenic stroke has been reported Does percutaneous PFO closure result in long-term stroke reduction after cryptogenic stroke? RESPECT

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36 RES P ECT: P a tie n t Flo w 36

37 RES P ECT Fin a l Re s u lts TM

38 RES P ECT Fin a l Re s u lts TM

39 Structural Heart Disease (PARTNER 2A and RESPECT): Implications Intermediate risk patients (STS 4) treated with the Sapien XT TAVR have comparable two-year outcomes to SAVR (RCT) and superior outcomes with the TF approach Intermediate risk patients (STS 4) treated with the Sapien S3 TAVR have superior two year outcomes to SAVR (Propensity matched) PFO closure for cryptogenic stroke lowers the long-term risk of stroke

40 Ac u te Myo c a rd ia l In fa rc tio n

41 Acute Myocardial Infarction (DANAMI 3) Thrombus burden in the culprit vessel is associated with noreflow during STEMI PCI Does a 48 hour deferred strategy for stenting during STEMI for culprit vessel TIMI 3 flow lead to smaller infarct size and superior long-term outcomes? DEFER Is there a role for ischemic post conditioning during STEMI PCI? ip OS T

42 Flow Chart DANAMI-3 STEMI Angiography TIMI 0-I TIMI 2-3 Randomization PCI TIMI 0-I PCI TIMI 2-3 Excluded Postcon Conv Defer

43 DANAMI-3 DEFERPrimary Endpoint 0.25 Primary endpoint HR: 0.99 [ ]; P= Event rate 0.20 Conventional Deferred Time (years) Number at risk Conventional 612 Deferred Primary endpoint:death, MI, utvrand CHFrehospitalization Kelbaek et al. Lancet 2016

44 Components of the primary endpoint Cumulative incidence HR: 0.83 [ ]; P=0.37 Conventional Deferred Time (years) Number at risk Conventional 612 Deferred 603 Hospitalisation for heart failure 2 3 Time (years) HR: 1.7 [ ]; P= Conventional Deferred Cumulative incidence HR: 0.82 [ ]; P=0.49 D 0.05 Conventional Deferred Unplanned target vessel revascularisation C Number at risk Conventional 612 Deferred 603 Cumulative incidence HR: 1.1 [ ]; P= Event rate Recurrent myocardial reinfarction B Conventional Deferred All cause mortality A Time (years) Number at risk Conventional 612 Deferred Time (years) Number at risk Conventional 612 Deferred

45 DANAMI 3-iPOST: Ischemic postconditioning Occluded coronary artery Reperfusion Reperfusion injury Conventional treatment Reperfusion injury Ischemic postconditioning Balloon inflations deflations sec

46 DANAMI3-iPOST A Conventional ipost HR: 0.93 [ ]; P= Event free survival 0.15 Primary endpoint Time (years) Number at risk Conventional 617 ipost Primary endpoint:death, MI, utvr and CHF rehospitalization median follow up 37.5 months

47 Acute Myocardial Infarction (DANAMI 3): Implications No benefits for a deferred strategy during primary PCI with a patent vessel or ischemic post conditioning

48 Ne w De vic e s /Te c h n o lo g y

49 New Devices/Technology Any new DES on the horizon for US? BIONICS Can short DAPT be used for DES? LEADERS FREE Any technology to address occupational hazard during complex PCI? CORA P CI

50 Bio NIR S ys te m Fla t m a n u fa c tu rin g Quality & cost efficiency Va ria b le s tru t wid fre q u e n c Uniform dosing - 80µm CoCr Wizecell design - Ridaforolimus high therapeutic index drug Ela s to m e ric P o lym e r: Remains intact S p rin g tip : Pushable & visible Me d in o l Ltd., Te l Aviv, Is ra e l

51 BIONICS Tria l De s ig n Mo re Co m e rs P o p u la tio n with S ym p to m a tic CAD (e g, NS TEMI, CTO, S VG, MVD) 76 Centers in NA, Europe, Israel FAS*:1919 patients randomized 1:1 BioNIR Stent N=958 Re s o lu te S te n t N=961 Noninferiority Design (Event rate 5.8%, Delta 3.3%, Power 90%) P rim a ry Clin ic a l En d p o in t Follow Up 30d 6m o 12m o 13m o 2yr QCA & Im a g in g En d p o in ts *FAS= Full Analysis Set 3yr 4yr 5yr

52 P ro c e d u ra l Ou tc o m e s Bio NIR N=958 patients, 1275 lesions Re s o lu te N=961 patients, 1277 lesions p va lu e Device Success 98.3% 99.5% Lesion Success 99.9% 99.8% 1.00 Procedure Success 97.7% 97.3% 0.57 De vic e s u c c e s s : final in-stent residual QCA diameter stenosis of <50% using the assigned device only and without a device malfunction Le s io n s u c c e s s : final in-stent residual QCA diameter stenosis of <50% using any percutaneous method P ro c e d u re s u c c e s s : final in-stent QCA diameter stenosis of <50% using the assigned device and/or with any adjunctive devices, without the occurrence of cardiac death, Q wave or non-q wave MI, or repeat revascularization of the target lesion during the hospital stay

53 BIONICS P rim a ry En d p o in t TLF a t 12 m o n th s 10 p n o n in fe rio rity = %TLF a t 12 m o. 8 6 Diffe re n c e =0% ( -, 1.8%) 5.3% 5.3% Bio NIR Re s o lu te Fa vo rs Bio NIR Fa vo rs Re s o lu te

54 BIONICS 12 m o Ke y En d p o in t Re s u lts Bio NIR N=958 Re s o lu te N= % (49/926) Cardiac Death Re la tive Ris k P va lu e 5.3%(49/930) 1.00 [0.68,1.48] % (5/926) 0.2% (2/930) 2.51 [0.49, 12.91] 0.29 TV-MI* 3.1% (29/926) 3.3% (31/930) 0.94 [0.57, 1.55] 0.81 ID-TLR 3.0% (28/926) 2.4% (22/930) 1.28 [0.74, 2.22] % (11/931) 1.1% (10/936) 1.11[0.47,2.59] 0.82 Target Lesion Failure (TLF) Total Mortality * SCAI definition for periprocedural MI, Moussa et al. JACC 2013

55 Bio Fre e d o m Dru g Co a te d S te n t (DCS) BA9 TM Dru g 10 Tim e s Mo re Lip o p h ilic th a n S iro limu s % Siro lim u s Zo taro lim u s Eve ro lim u s +/- 2.8% (valid for all drugs test) Ad va n ta g e s : Avoid any possible polymer-related adverse effects Rapid drug transfer to vessel wall (98% within one month2) Good fit with short DAPT 1. Da ta o n file a t Bio s e n s o rs In tl; 2. Ta d a e t a l., Circ Ca rd io va s c In te rv 2010;3; Bio lim u s A9 TM

56 LEADERS FREE Tria l De s ig n P ro s p e c tive, d o u b le -b lin d ra n d o m ize d (1:1) tria l 2466 Hig h b le e d in g ris k (HBR) P CI p a tie n ts Bio Fre e d o m DCS vs. Ga ze lle BMS P rim a ry s a fe ty e n d p o in t: Composite of cardiac death, MI, definite / probable stent thrombosis at 1 year (non-inferiority then superiority) P rim a ry e ffic a c y e n d p o in t: Clinically-driven TLR at 1 year (superiority)

57 P rim a ry S a fe ty En d p o in t (Cardiac Death, MI, ST) at 2 year Patients with Event (%) % % Days DCS BMS Nu m b e r a t Ris k Garot et al; JACC year FU was obtained at 730 days + 60 days

58 P rim a ry Effic a c y En d p o in t (Clinically-Driven TLR) at 2 Years Patients with Event (%) % % Days DCS BMS Nu m b e r a t Ris k 2 year FU was obtained at 730 days + 60 days

59 What is Robotic PCI? FDA approved technology (CorPath 200, Corindus Vascular, Waltham, MA) Significant change in how the procedure is performed Re m o te c o n tro l o f d e vic e s g u id e wire s b a llo o n s s te n ts Physician seated Facilitated visualization Precise lesion measurement

60 Robotic Cassette

61 CORA-PCI (Complex Robotically Assisted PCI) Trial Hyp o th e s is : Robotic PCI can be performed in patients with complex coronary artery disease S tu d y g ro u p : Consecutive robotic PCI procedures over 18 months by single operator/center Co n tro l g ro u p : Consecutive manual PCI procedures over 18 months by same operator/center In c lu s io n c rite ria : all comers with left main, ostial, bifurcation, multivessel, CTO, saphenous vein graft, depressed LV function, Impella or IABP supported, radial or femoral access Exc lu s io n c rite ria : procedures ineligible for robotic PCI due to technical limitations of the robotic platform i.e. over the wire approach required, planned atherectomy, or thrombectomy Mahmud et al; SCAI 2016 Late Breaker Clinical Trial

62 CORA-PCI (Complex Robotically Assisted PCI) Trial: Study Flow P CI proc e du re s (n =413) Excluded from manual PCI group (n=79) STEMI Planned bifurcation stent Hybrid CTO Atherectomy Ro bo tic PCI (N=108; 157 le s ion s ) Ma n ua l P CI (N=226; 336 le s ion s )

63 Robotic Technical Success 91.7% Mahmud et al; SCAI 2016 Late Breaker Clinical Trial

64 Primary Endpoint: Clinical Success P=0.64 Procedural Success with Freedom from In-hospital MACE* (%) Robotic PCI Manual PCI * MACE: death, stroke, urgent revascularization or MI (SCAI definition: CK-MB>5x ULN with clinical evidence of ischemia)

65 Secondary Endpoint: Freedom from Periprocedural Myocardial Infarction (Universal Definition) Percent Freedom from Periprocedural MI 100 P= Robotic PCI Manual PCI * Periprocedural MI: CK-MB>3x ULN

66 New Devices/Technology: Lessons and Implications A new potential DES with outcomes comparable to the Resolute DES has been studied in the US The BioFreedom abluminal DCS requires 30 days DAPT and has efficacy and safety outcomes superior to a BMS Robotic PCI is feasible and safe for complex lesions and could address the occupational hazard for the interventionalist

67 Bio a b s o rb a b le Va s c u la r S c a ffo ld s

68 Bioresorbable Vascular Scaffolds Intermediate effect on vasomotor tone and safety ABS ORB II Intermediate clinical outcomes ABS ORB CHINA

69 Co -p rim a ry e n d p o in t: in -d e vic e va s o m o tio n in ABS ORB II Cu m u la tive fre q u e n c y d is trib u tio n c u rve s o f va s o m o tio n a t 3 ye a rs Ch a n g e in m e a n lu m e n d ia m e t e r Cumulative frequency Ab s o rb 0.5 n = ± m m XI ENCE n = ± m m 0.4 Psuperiority = Serruys et al; Lancet Vasomotion (mm)

70 Co -p rim a ry e n d p o in t: a n g io g ra p h ic la te lu m in a l lo s s Cu m u la tive fre q u e n c y d is trib u tio n c u rve s o f la te lu m in a l lo s s a t 3 ye a rs Ac u te S c T (n =1) S u b a c u te S c T (n =1) La te S c T (n =1) NI Ma r g in Ve ry La te S c T (n =6) Cumulative frequency mm XIENCE n= ± % CI ( ) 0.4 Absorb n= ±0.449 P n o n -in mm fe rio rity = P non-inferiority = Late luminal loss (in-stent/ scaffold) (mm) 2.5 3

71 S c a ffo ld o r s te n t th ro m b o s is 2 : 1 ra n d o m iza tio n Absorb 335 patients Xience 166 patients p value 2 5% (8) 0 0% (0) 0 06 Ac u te (0 1 d a y) 0 3% (1) 0 0% (0) 1 0 S u b -a c u te (2 30 d a ys ) 0 3% (1) 0 0% (0) 1 0 La te ( d a ys ) 0 0% (0) 0 0% (0) 1 0 Ve ry la te (>365 d a ys ) 1 8% (6) 0 0% (0) 0 19 S u b -a c u te (2 30 d a ys ) 0 3% (1) 0 0% (0) 1 0 La t e ( d a ys ) 0 3 % ( 1 ) 0 0 % ( 0 ) 1 0 Very late (>365 days) 1 8% (6) 0 0% (0) 0 19 De fin ite

72 Du a l a n tip la te le t th e ra p y Ab s o rb 335 p a tie n ts 30.5% 566 d a ys Patients on DAPT at day 1095 Overall duration (day) of DAPT Xie n c e 166 p a tie n ts 29.5% 561 d a ys p va lu e DAP T u s e in s c a ffo ld th ro m b o s is c a s e s DAPT use Tim e ( d a y) AST 0 SAST 2 LST 335 Scaffold thrombosis no VLS T VLS T Ab s o rb P ro b a b le Th ro m b o lys is VLST DAP T 3y with o u t in te rru p tio n 63 0 DAP T with in te rru p tio n VLST unknown VLST VLST VLST p = VLST Time to event (days) Fis h e r s e xac t te s t Th e p a tien ts with la te o r very la te s c a ffo ld th ro m b o s is we re n o t o n DAP T.

73 Ka p la n Me ie r c u rve s fo r De vic e - a n d P a tie n t- o rie n te d c o m p o s ite e n d p o in ts (DOCE a n d P OCE) Ca rd ia c d e a th TV-MI CI-TLR Absorb P OCE Xience HR[95%CI] 2.17 [1.01, 4.69] p= % % ent oriented clinical endpoint (%) ce oriented clinical endpoint (%) DOCE All-c a u s e d e a th An y-mi An y re va s c u la riza tio n Absorb 24.0% Xience HR[95%CI] 0.86 [0.58, 1.27] p= % 5 Th re e -ye a r p ro to c o l m a n d a te d im a g in g trig g e re d s u b s e q u e n t re va s c u la riza tio n s, c lin ic a lly in d ic a te d o r n o t.

74 Clin ic a l e n d p o in ts No n -h ie ra rc h ic a l De vic e -o rie n te d c o m p o s ite e n d p o in t [DOCE] Ca rd ia c d e a th Ta rg e t ve s s e l MI P e rip ro c e d u ra l MI (WHO) S p o n ta n e o u s MI (WHO e xte n d e d ) Clin ic a lly in d ic a te d TLR 2 : 1 ra n d o m iza tio n Ab s o rb 325 p a tie n ts Xien c e 161 p a tie n ts Re la tive Ris k p va lu e 10.5% 5.0% 2 11 [ 1 00, 4 44] % 7.1% (23) 3.9%(13) 3.1% (10) 6.2%(20) 1.9% 1.2% (2) 1.2% (2) 0% (0) 1.9% (3) 0 50 [ 0 10, 2 43] [ 1.36, 23.87] [ 0.74, 14.11] 0.16 NC [ NC] [ 1.00, 10.95] P a tie n t-o rie n te d c o m p o s ite e n d p o in t [P OCE] O t 20.9% f 2 0 CI TLR 8 h d d fi it An y re n. pva r es csuelanriza t atio t ion 15.1% 0 86 [ 0 61, 1 22] % ff ld t h b i it h 20.5% 0.74 [ 0.49, 1.10] 0.13 Th e fin d in g s o f h ig h e r n o n - clin ica lly d r ive n TVR/ TLR r a t e s fo r Xie n ce co u ld h a ve b e e n ond et ad nn ea tou ren dt ioune. Un t o bslin cad ffold t hicia ronms bmos a t t r ib uou t e d tt ooft h1e 0u nsbplin u res omi f t h,e9inw t eer ve e d p h ys a yis be r ob len)t rao lngdr o1u pd in e fin om s is p ro n e t(o8 redaedfin ily it ree-inatne rdve1n ep in t hae bco p a it t ieen tt sh trre a t ebdow it h ca Xiesnece, w h e r e adsiet hde.yth m ig bea e nlsuon co t ot in r ve e inrdt hiaec d e a t h ish tcah asve e is t anbsucio lautselyd reinlu tcthaen tca e gt eor y nca e x p e r im e n t a l d e vice a r m ( Ab s o r b ), a lt h o u g h t h is a s s u m p t io n is p u r e ly s p e cu la t ive a n d in t h e h ie r a r ch ica l p re s e n t a t io n. h a s n o t b e e n o b je ct ive ly d o cu m e n t e d.

75 Clin ic a l e n d p o in ts Hie ra rc h ic a l De vic e -o rie n te d c o m p o s ite e n d p o in t [DOCE] Ca rd ia c d e a th Ta rg e t ve s s e l MI P e rip ro c e d u ra l MI (WHO) S p o n ta n e o u s MI (WHO e xte n d e d ) Clin ic a lly in d ic a te d TLR P a tie n t-o rie n te d c o m p o s ite e n d p o in t [P OCE] y 2 : 1 ra n d o m iza tio n Ab s o rb 325 p atie n ts Xien c e 161 p a tie n ts Re la tive Ris k p va lu e 10.5% 5.0% 2 11 [ 1 00, 4 44] % 6.5% (21) 3.9%(13) 2.5% (8) 3.1% (10) 1.9% 1.2% (2) 1.2% (2) 0% (0) 1.9% (3) 0 50 [ 0 10, 2 43] [1 23, 21 91] [ 0.74, 14.11] 0.16 NC [ NC] [ 0 46, 5 92] % 24.2% 0 86 [ 0 61, 1 22] % 17.4% 0 62 [ 0 39, 0 98] 0.04 Th e fin d in g s o f h ig h e r n o n - clin ica lly d r ive n TVR/ TLR r a t e s fo r Xie n ce co u ld h a ve b e e n a t t r ib u t e d t o t h e u n b lin d e d n a t u re o f t h e in t e r ve n t io n. Un b lin d e d p h ys icia n s m a y b e p ro n e t o re a d ily re -in t e r ve n e in t h e co n t r o l g r o u p in p a t ie n t s t re a t e d w it h Xie n ce, w h e r e a s t h e y m ig h t h a ve b e e n u n co n s cio u s ly re lu ct a n t t o in t e r ve n e in t h e e x p e r im e n t a l d e vice a r m ( Ab s o r b ), a lt h o u g h t h is a s s u m p t io n is p u r e ly s p e cu la t ive a n d h a s n o t b e e n o b je ct ive ly d o cu m e n t e d.

76 ABS ORB Ch in a

77 P rim a ry En d p o in t: In-Segment Late Loss at 1 Year (PTE) PTE=459 subjects; 86.3% had the angiogram for the Primary Endpoint Analysis

78 2-Ye a r Clin ic a l Co m p o s ite En d p o in ts Ab s o rb BVS XIENCE V (N=241) (N=239) P -Va lu e PoCE (DMR) 10.1% (24/237) 11.4% (27/237) 0.66 DoCE (TLF) 4.2% (10/237) 4.6% (11/237) 0.82 MACE 5.1% (12/237) 5.1% (12/237) 1.00 TVF 5.5% (13/237) 6.8% (16/237) 0.57 oce=device oriented composite endpoin

79 S c a ffo ld /S te n t Th ro m b o s is Ab s o rb BVS XIENCE V (N=241) (N=239) 0.8% (2/237) 0.0% (0/231) 0.50 Definite 0.4% (1/237) 0.0% (0/231) 1.00 Probable 0.4% (1/237) 0.0% (0/231) 1.00 Early (0 30 days) 0.4% (1/238) 0.0% (0/236) 1.00 Late ( days) 0.0% (0/238) 0.0% (0/232) 1.00 Very Late ( days) 0.4% (1/237) 0.0% (0/231) 1.00 All (0-730 days) P -Va lu e Th e re we re 1 p ro b a b le, s u b a c u te (1-30d ) S T a n d 1 d e fin ite, ve ry la te S T in th e Ab s o rb BVS a rm.

80 Bioresorbable Vascular Scaffolds (ABSORB II and ABSORB China): Lessons and Implications No measureable effect on vasomotor function Very late stent thrombosis observed at 3 years in ABSORB II and single patient in ABSORB China Deployment technique and appropriate vessel sizing critical for success of BVS Role of longer term DAPT? Need longer term follow-up studies

81 Conclusions: Trials of 2016 Left main PCI is a viable option in selected patients TAVR with Sapien XT/S3 for intermediate-risk surgical patients has comparable outcomes to SAVR PFO closure reduces long-term risk of recurrent stroke after cryptogenic stroke No role for deferred PCI or ischemic post conditioning during primary PCI An alternative DES and a newer generation DCS (shorter DAPT) is on the horizon Robotic PCI is safe and feasible for complex PCI Optimal technique is critical during BVS stent placement; caution should be exercised as very late stent thrombois has been reported

82 Thank You!