0730 Clinical Trials Scripps 2016 - Promedica International · Key Clinical Trials In Interventional Cardiology: 2016 • Left Main Disease (PCI vs CABG): EXCEL, NOBLE • Structural

Ehtisham Mahmud, MD, FACC, FSCAI

Professor and Division Chief, Cardiovascular Medicine

Director, Sulpizio Cardiovascular Center-Medicine

University of California San Diego

Show me the Data : Key Clin ica l Tria ls of 2016

Disclosures

• Clinical trial support: Boston Scientific, Corindus, Medinol

• Consulting: St Jude, Corindus, Medtronic

• Equity/Stock Options: Abiomed, Ra Medical

• Speakers Bureau: Medtronic, Abbott Vascular

Key Clinical Trials In Interventional Cardiology: 2016

• Left Main Dis eas e (PCI vs CABG): EXCEL, NOBLE

• Struc tura l Heart Dis eas e : PARTNER 2A, RESPECT

• Acute Myoca rd ia l In fa rc tion : DANAMI-3 DEFER, DANAMI-3 POST

• New Devices /Technology: BIONICS, LEADERS FREE, CORA PCI

• BVS : ABSORB II, ABSORB CHINA

LEFT MAIN DISEASE: PCI VS CABG

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

R

EXCEL: Study Des ign

SYNTAX Score

Site Reported Core LabLow (≤22)

Intermediate (23-32)

High (≥33)

PCI

CABG

59.2%40.8%

61.8%38.2%

Mean 20.6 ± 6.2

Mean 20.5 ± 6.1

P =0.52

42.8%

25.1%

32.2%

37.3%

23.4%

39.3%

Mean 26.9 ± 8.8

Mean 26.0 ± 9.8

P =0.005

Primary Endpoin tDeath , S troke or MI at 3 Years

No. at Risk:

PCI

CABG

5%

25%

20%

15%

10%

0%

1 6 12 24 36

850

817

784

763

445

458

HR [95%CI] =1.00 [95% CI: 0.79, 1.26]

P = 0.98

875

836

0

948

957

896

868

15.4%14.7%

De

ath

,s

tro

ke

or

MI

(%)

CABG (n=957)

PCI (n=948)

Months

PCI(n=948)

CABG(n=957)

Diff [upperconfidence limit]

P NI HR [95%CI] P Sup

Primary endpo in t

Death, stroke or MIat 3 years

15.4% 14.7% 0.7% [4.0%]† 0.018 - -

Secondary endpoin ts

Death, stroke or MIat 30 days

4.9% 7.9% -3.1% [-1.2%]†† <0.001 - -

Death, stroke, MI orischemia-driven revascat 3 years

23.1% 19.1% 4.0% [7.2%]†† 0.01 - -


15.4% 14.7% - - 1.00 [0.79, 1.26] 0.98

Primary and Hiera rch ica lSecondary Clin ica l Outcomes

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.Stone et al; NEJM 2016

PCI(n=948)

CABG(n=957)



Primary endpo in t


15.4% 14.7% 0.7% [4.0%]† 0.018 - -



4.9% 7.9% -3.1% [-1.2%]†† <0.001 - -


23.1% 19.1% 4.0% [7.2%]†† 0.01 - -


15.4% 14.7% - - 1.00 [0.79, 1.26] 0.98



†Upper 97.5% confidence limit; ††Upper 95.0% confidence limit.

PCI(n=948)

CABG(n=957)



Primary endpo in t


15.4% 14.7% 0.7% [4.0%]† 0.018 - -



4.9% 7.9% -3.1% [-1.2%]†† <0.001 - -


23.1% 19.1% 4.0% [7.2%]†† 0.01 - -


15.4% 14.7% - - 1.00 [0.79, 1.26] 0.98




PCI(n=948)

CABG(n=957)



Primary endpo in t


15.4% 14.7% 0.7% [4.0%]† 0.018 - -



4.9% 7.9% -3.1% [-1.2%]†† <0.001 - -


23.1% 19.1% 4.0% [7.2%]†† 0.01 - -


15.4% 14.7% - - 1.00 [0.79, 1.26] 0.98




PCI(n=948)

CABG(n=957)



Primary endpo in t


15.4% 14.7% 0.7% [4.0%]† 0.018 - -



4.9% 7.9% -3.1% [-1.2%]†† <0.001 - -


23.1% 19.1% 4.0% [7.2%]†† 0.01 - -


15.4% 14.7% - - 1.00 [0.79, 1.26] 0.98




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] 0.98

- Death 8.2% 5.9% 1.34 [0.94, 1.91] 0.11

- Definite cardiovascular 3.7% 3.4% 1.10 [0.67, 1.80] 0.71

- Definite non-cardiovascular 3.9% 2.3% 1.60 [0.91, 2.80] 0.10

- Undetermined cause 0.8% 0.3% 2.00 [0.50, 7.98] 0.32

- Stroke 2.3% 2.9% 0.77 [0.43, 1.37] 0.37

- MI 8.0% 8.3% 0.93 [0.67, 1.28] 0.64

- Peri-procedural 3.8% 6.0% 0.63 [0.42, 0.96] 0.03

- Spontaneous 4.3% 2.7% 1.60 [0.95, 2.70] 0.07

- STEMI 1.3% 2.8% 0.46 [0.23, 0.91] 0.02

- Non-STEMI 7.0% 5.9% 1.15 [0.80, 1.65] 0.46

Adjud ica ted Outcomes a t 3 Years (i)

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] 0.10

- Ischemia-driven revasc (IDR) 12.6% 7.5% 1.72 [1.27, 2.33] <0.001

- PCI 10.3% 6.8% 1.57 [1.13, 2.18] 0.006

- 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% - <0.001

- Definite 0.7% 0.0% - 0.01

- Probable 0.7% 0.0% - 0.01

- Early (0 - 30 days) 0.7% 0.0% - 0.008

- Late (30 days – 1 year) 0.1% 0.0% - 0.32

- Very late (1 year - 3 years) 0.5% 0.0% - 0.05

Graft occlusion, symptomatic 0.0% 5.4% - <0.001

Definite stent thrombosis orsymptomatic graft occlusion

0.7% 5.4% 0.12 [0.05, 0.28] <0.001

Adjudica ted 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] 0.10

- Ischemia-driven revasc (IDR) 12.6% 7.5% 1.72 [1.27, 2.33] <0.001

- PCI 10.3% 6.8% 1.57 [1.13, 2.18] 0.006

- 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% - <0.001

- Definite 0.7% 0.0% - 0.01

- Probable 0.7% 0.0% - 0.01

- Early (0 - 30 days) 0.7% 0.0% - 0.008

- Late (30 days – 1 year) 0.1% 0.0% - 0.32

- Very late (1 year - 3 years) 0.5% 0.0% - 0.05

Graft occlusion, symptomatic 0.0% 5.4% - <0.001

Definite stent thrombosis orsymptomatic graft occlusion

0.7% 5.4% 0.12 [0.05, 0.28] <0.001

Adjudica ted Outcomes at 3 Years (ii)

Patientsallocated to CABGin analysis(n=592)

567received CABG23received PCI

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)

Allocated to CABG(n=603)• Received CABG(n=570 )• Did not receiveCABG(n=33)

• Died beforeCABG(n=1)• Patient declinedCABG(n=15)• Not eligible for CABG(n=15)• Crossover by mistake(n=2)

Lost to follow-up(n=6)• Emigration (n=1)• Contact lost (n=2)• Withdrawal (n=3)

Lost to follow-up(n=11)• Emigration (n=0)• Contact lost (n=0)• Withdrawal (n=11)

Pat ientsallocated to PCI (BiolimusDES) in analysis (n=592)

580 received PCI7received CABG

Christiansen et al; Lancet 2016

Primary endpoint: MACCE(Death, MI, Stroke andRepeat Revascularization)

HR1·48 (1·11–1·96); p=0·006628·9%

19·1%

PCI did not show non-inferiorityand CABGwassuperior to PCI

Christiansen et al; Lancet 2016

All-cause mortality

11.5%

9.5%

HR1·07(0·67–1·72); p=0·77

11·6%

9·5%

Non-procedural myocardial infarct ion

HR2·88 (1·40–5·90); p=0·004

6·9%

1·9%

Stroke

HR2·25 (0·92–5·48); p=0·07

4·9%

1·7%

Total repeat revascularizat ion

HR1·50 (1·04–2·17); p=0·03

10·4%

16·2%

Kaplan-Meier 5 year estimates byintention-to-treat

4.9%

1.9%

K-M estimates

Kaplan-Meier 5 year estimates byintention-to-treat

4.9%

1.9%

K-M estimates

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

Struc tura l Heart Dis eas e

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

RESPECT: Patien t Flow

36

RESPECT Final Res ults

TM

RESPECT Final Res ults

TM

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

Acute Myocard ia l Infa rc tion

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?

iPOST

TIMI 0-I TIMI 2-3

Postcon

TIMI 0-I

PCI

TIMI 2-3

DeferConv

STEMI

Angiography

Randomization

Excluded

Flow Chart DANAMI-3

PCI

0.00

0.05

0.10

0.15

0.20

0.25

Even

trat

e

603 543 526 359 156 0Deferred612 568 533 360 159 0Conventional

Number at risk

0 1 2 3 4 5

Time (years)

Conventional

DeferredHR: 0.99 [0.75-1.29]; P=0.92

Primary endpoint

DANAMI-3 DEFERPrimary Endpoint

Primary endpoint:Death, MI, uTVRand CHFrehospitalization

Kelbaek et al. Lancet 2016

0.0

00

.05

0.1

00.1

50

.20

0.2

5

Eve

ntra

te


Number at risk

0 1 2 3 4 5

Time (years)

Conventional

Deferred

A

HR: 0.83 [0.56 - 1.24]; P=0.37

All cause mortality

0.0

00

.05

0.1

00

.15

0.2

00

.25

Cu

mu

lativ

ein

cid

en

ce


Number at risk

0 1 2 3 4 5

Time (years)

Conventional

Deferred

C

HR: 0.82 [0.47 - 1.43]; P=0.49

Hospitalisation for heart failure

0.0

00

.05

0.1

00

.15

0.2

00

.25

Cum

ula

tive

incid

en

ce


Number at risk

0 1 2 3 4 5

Time (years)

Conventional

Deferred

B

HR: 1.1 [0.69 - 1.64]; P=0.77

Recurrent myocardial reinfarction

0.0

00

.05

0.1

00

.15

0.2

00

.25

Cum

ula

tive

incid

ence


Number at risk

0 1 2 3 4 5

Time (years)

Conventional

Deferred

D

HR: 1.7 [1.04 - 2.92]; P=0.03

Unplanned target vessel revascularisation

Componentsof the primary endpoint

Conventionaltreatment

coronary arteryReperfusionOccluded

Reperfusioninjury

ReperfusioninjuryIschemic

postconditioning30 30 30 sec3030 30 30 30

Balloon inflations–deflations

DANAMI 3-iPOST: Ischemic postconditioning

Primary endpoint:Death, MI, uTVR and CHF rehospitalization–median followup 37.5 months

DANAMI3-iPOST

0.0

00

.05

0.1

00

.15

1-

Eve

ntfr

ee

surv

iva

l

617 586 580 575 566 409 292iPOST617 579 572 560 551 415 295Conventional

Number at risk

0 6 12 18 24 30 36

Time (years)

Conventional

iPOST

A

HR: 0.93 [0.66 - 1.30]; P=0.66

Primary endpoint

Acute Myocardial Infarction (DANAMI 3): Implications

• No benefits for a deferred strategy during primary PCI with a patent vessel or ischemic post

conditioning

New Devices /Technology

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 PCI

Fla tmanufac turingQuality & costefficiency

- 80µm CoCr Wizecell design- Ridaforolimus high therapeutic indexdrug

Elas tomeric Polymer: Remains intact Spring tip : Pushable & visible

Variab les tru t widfrequencUniformdosing

Medinol Ltd ., Te l Aviv, Is rae l

BioNIR Sys tem

30d 6mo 4yr3yr2yr12mo 13mo 5yr

BioNIR StentN=958

Res olu te Sten tN=961

76 Centers in NA, Europe, IsraelFAS*:1919 patients randomized 1:1

Prim ary Clinical Endpoint

“ More Comers ” Popula tion withSymptomatic CAD

(eg , NSTEMI, CTO, SVG, MVD)

QCA & Imaging Endpoints

BIONICS – Tria l Des ign

Follow Up

Noninferiority Design(Event rate 5.8%, Delta 3.3%, Power 90%)

*FAS= Full Analysis Set

Procedura l Outcomes

BioNIRN=958 patients,

1275 lesions

Res olu teN=961 patients,

1277 lesions p va lue

Device Success 98.3% 99.5% 0.004

Lesion Success 99.9% 99.8% 1.00

Procedure Success 97.7% 97.3% 0.57

Device s ucces s : final in-stent residual QCA diameter stenosis of <50% using the assigned deviceonly and without a device malfunctionLes ion s ucces s : final in-stent residual QCA diameter stenosis of <50% using any percutaneousmethodP rocedure s ucces s : final in-stent QCA diameter stenosis of <50% using the assigned deviceand/or with any adjunctive devices, without the occurrence of cardiac death, Q wave or non-Qwave MI, or repeat revascularization of the target lesion during the hospital stay

BIONICS – Primary Endpoin t

TLF a t 12 months

Diffe rence=0% ( - , 1.8%)

%T

LF

at

12

mo

.10

8

6

4

2

0

BioNIR

5.3%

Res olute

5.3%

3.3

FavorsBioNIR

FavorsRes olu te

0

p non in ferio rity=0.0012

BIONICS12 mo Key Endpoin t Res ults

BioNIRN=958

Res olu teN=961 Rela tive Ris k P va lue

Target LesionFailure (TLF)

5.3% (49/926) 5.3%(49/930)1.00

[0.68,1.48]0.98

CardiacDeath

0.5% (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]0.38

Total Mortality 1.2% (11/931) 1.1% (10/936) 1.11[0.47,2.59] 0.82

* SCAI definition for periprocedural MI, Moussa et al. JACC 2013

BioFreedom™ Drug Coated Stent (DCS)

Advantages :• Avoid any possible polymer-related adverse effects

• Rapid drug transfer to vessel wall (98% within one month2)

• Good fit with short DAPT

BA9TM Drug 10 Times MoreLipophilic than Siro limus 1

Sirolimus Zotarolimus Evero lim us Bio lim us A9TM

0

20

40

60

80

100 %

+/- 2.8% (valid for all drugs test)

1. Data on file a t Bios e ns ors Intl;2. Ta da e t a l., Circ Ca rd iovas c Inte rv 2010;3;174-183

LEADERS FREE Tria l Des ign

Pros pective , doub le -b lind randomized (1:1) tria l2466 High b leed ing ris k (HBR) PCI pa tien ts

vs.BioFreedom™DCS

Gaze lle™BMS

• Primary s afe ty endpoin t:Composite of cardiac death, MI, definite / probable stent thrombosisat 1 year (non-inferiority then superiority)

• Primary efficacy endpo in t:Clinically-driven TLR at 1 year (superiority)

Primary Safe ty Endpoin t(Cardiac Death, MI, ST) at 2 year

0

180 365 545 730

Pa

tients

with

Eve

nt

(%)

5

10

15

Days0

15.3%

12.6%

20

Num ber at Ris k

DCS 1221 1104 1052 1006 620

BMS 1211 1067 1010 973 587

2 year FU was obtained at 730 days + 60 days

Garot et al; JACC 2016

Primary Efficacy Endpoin t(Clinically-Driven TLR) at 2 Years

0

Pa

tients

with

Eve

nt

(%)

5

10

15

12.0%

6.8%

20

Num ber at Ris k

DCS 1221 1129 1061 1013 626

BMS 1211 1074 999 945 561

180 365 545 730 Days0

2 year FU was obtained at 730 days + 60 days

What is Robotic PCI?

• FDA approved technology (CorPath200, Corindus Vascular, Waltham, MA)

• Significant change in how theprocedure is performed

– Remote contro l of devices

• guidewires

• balloons

• s ten ts

– Physician seated

– Facilitated visualization

– Precise lesion measurement

Robotic Cassette

CORA-PCI (Complex Robotically Assisted PCI) Trial

• Hypothes is : Robotic PCI can be performed in patients with complex coronary artery disease

• Study group : Consecutive robotic PCI procedures over 18 months by single operator/center

• Contro l group: Consecutive manual PCI procedures over 18 months by same operator/center

• Inc lus ion crite ria : all comers with left main, ostial, bifurcation, multivessel, CTO, saphenous

vein graft, depressed LV function, Impella or IABP supported, radial or femoral access

• Exclus ion crite 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

PCI procedures (n=413)

Robotic PCI

(N=108; 157 les ions )

Manual PCI

(N=226; 336 les ions )

Excluded from manual PCI group (n=79)

STEMI

Planned bifurcation stent

Hybrid CTO

Atherectomy

CORA-PCI (Complex Robotically Assisted PCI) Trial: Study Flow

Robotic Technical Success

91.7%

Mahmud et al; SCAI 2016 Late Breaker Clinical Trial

Primary Endpoint: Clinical Success

0

10

20

30

40

50

60

70

80

90

100

RoboticPCI Manual PCI

Pro

cedura

lSucc

ess

wit

hFr

eedom

from

In-h

osp

ital

MA

CE*

(%)

P=0.64

*MACE: death, stroke, urgent revascularization or MI (SCAI definition: CK-MB>5x ULN with clinical evidence of ischemia)

Secondary Endpoint: Freedom from PeriproceduralMyocardial Infarction (Universal Definition)

0

10

20

30

40

50

60

70

80

90

100

Robotic PCI Manual PCI

Perc

ent

Freedom

from

Peri

pro

cedura

lMI

P=0.32

*Periprocedural MI: CK-MB>3x ULN

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

Bioabs orbable Vas cular Scaffo lds

Bioresorbable Vascular Scaffolds

• Intermediate effect on vasomotor tone and safety

ABSORB II

• Intermediate clinical outcomes

ABSORB CHINA

0

0 1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

-0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 0.8 1

Cum

ula

tive

freq

uency

Ab s orb n= 2 5 8 0 .0 4 7 ± 0 .1 0 9 m m

XI ENCE n= 1 3 0 0 .0 5 6 ± 0 .1 1 7 m m

Psuperiority = 0.49

Vasomotion (mm)

Co-primary endpoin t: in -device vas omotion in ABSORB IICumula tive frequency dis tribu tion curves of vas omotion a t 3 years

Ch a n g e in m e a n lu m e n d ia m e t e r

Serruys et al; Lancet 2016

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

-1 -0.5 0 0.5 1 1.5 2 2.5 3

Cum

ula

tive

frequency

Late luminal loss(in-stent/ scaffold) (mm)

XIENCE n=151 0.250±0.250 mm

Pnon-inferiority = 0.78

Absorb n=298 0.371±0.449 mm

NI Ma rg in

0 .1 4

9 5 % CI (0 .0 6 – 0 .1 9 )

0

0.12

P non-inferiority = 0.78

Acute ScT (n=1)

Subacute ScT (n=1)

Late ScT (n=1)

Very Late ScT (n=6)

Co-primary endpoin t: angiographic la te lumina l los sCumula tive frequency dis tribu tion curves of la te lumina l los s a t 3 years

Absorb335 patients

Xience166 patients

p value

Defin ite 2·5% (8) 0·0% (0) 0·06

Acute (0–1 day) 0·3% (1) 0·0% (0) 1·0

Sub-acute (2–30 days ) 0·3% (1) 0·0% (0) 1·0

Late (31–365 days ) 0·0% (0) 0·0% (0) 1·0

Very la te (>365 days ) 1·8% (6) 0·0% (0) 0·19

Scaffo ld or s ten t thrombos is

Sub-acute (2–30 days ) 0·3% (1) 0·0% (0) 1·0

La t e (3 1 –3 6 5 d a ys ) 0 ·3 % (1 ) 0 ·0 % (0 ) 1 ·0

Very late (>365 days) 1·8% (6) 0·0% (0) 0·19

2 : 1 randomiza tion

Abs orb335 patien ts

Xience166 patien ts

p value

Patients on DAPT at day 1095 30.5% 29.5% 0·81

Overall duration (day) of DAPT 566 days 561 days 0·88

Dual antip la te le t the rapy

Tim e(da y)

AST 0

SAST 2

LST 33 5

VLST 44 7

VLST 60 2

VLST 96 7

VLST 98 1

VLST 1 02 2

VLST 1 08 2

Scaffold thrombosis

Time to event (days)

DAPTuse

unknown

DAPT us e in s caffo ld thrombos is cas es

The patien ts with la te or very la te s caffo ld thrombos is were not on DAPT.

Abs orbno

VLSTVLST

DAPT 3ywithout

in te rrup tion63 0

DAPT within te rrup tion 266 6

p = 0.599

Fis her ’s exac t tes t

Proba b leThrombolys is

Kaplan Meier curves for Device - and Pa tien t- o rien tedcompos ite endpoin ts (DOCE and POCE)

ent

ori

ente

dcl

inic

ale

ndpoin

t(%

)

Absorb Xience25

20

15

10

5

HR[95%CI]0.86 [0.58, 1.27]p=0.44

20.8%

24.0%ce

ori

ente

dcl

inic

alendpoin

t(%

)

Absorb Xience25

20

15

10

5

HR[95%CI]2.17 [1.01, 4.69]p=0.043

4.9%

10.4%

POCEDOCE

Three -yea r pro tocol mandated imaging triggereds ubs equent revas cula riza tions , c lin ica lly ind ica ted or not.

Card iac dea thTV-MICI-TLR

All-caus e deathAny-MIAny revas cularization

Non-hierarchica lAbs orb

325 patien tsXience

161 pa tien tsRela tive Ris k p value

Device -oriented com pos ite endpoint[DOCE] 10.5% 5.0% 2·11 [1·00, 4·44] 0·04

Cardiac death 0.9% 1.9% 0·50 [0·10, 2·43] 0·40

Targe t ves s el MI 7.1% (23) 1.2% (2) 5.70 [1.36, 23.87] 0.0061

Perip ro cedura l MI (WHO) 3.9%(13) 1.2% (2) 3.22 [0.74, 14.11] 0.16

Spontaneo us MI (WHO extended ) 3.1% (10) 0% (0) NC [NC] 0.06

Clinically indicated TLR 6.2%(20) 1.9% (3) 3.30 [1.00, 10.95] 0.036

Patient-oriented compos iteendpoin t [POCE] 20.9% 24.2% 0·86 [0·61, 1·22] 0·40

Any revas culariza tion 15.1% 20.5% 0.74 [0.49, 1.10] 0.13

Th e fin d ings of h igh e r non -clin ica lly d r ive n TVR/ TLR ra t e s for Xie nce cou ld h a ve b e e n

a t t r ibu t e d t o t h e u n b lin de d na t u re of t h e in t e rve n t ion . Unb lin de d ph ys icia ns m a y be

p rone t o re a d ily re -in t e rve ne in t h e con t ro l g rou p in pa t ie n t s t re a t e d w it h Xie nce ,

w h e re a s t h e y m igh t h a ve b e e n u n cons ciou s ly re lu ct a n t t o in t e rve ne in t h e

e xpe r im e n t a l d e vice a rm (Abs orb ) , a lt h ou gh t h is a s s u m pt ion is pu re ly s p e cu la t ive a nd

h a s not be e n ob je ct ive ly docu m e n t e d .

O t f 2 0 CI TLR 8 h d d fi it ff ld t h b i it h

p re s e n t a t ion .

• Ou t of 1 0 s p on t a n e ou s MI , 9 w e re d u e t o s ca ffold t h rom b os is(8 d e fin it e a n d 1 p rob a b le ) a n d 1 d e fin it e t h rom b os is ca s ed ie d . Th is ca s e is a ls o t a b u la t e d in t h e ca t e g ory ca rd ia c d e a t hin t h e h ie ra rch ica l p re s e n t a t ion .

2 : 1 randomiza tionClin ica l endpoin ts

Hiera rch ica lAbs orb

325 patien tsXience

161 patien tsRela tive Ris k p value

Device -oriented com pos ite endpo int[DOCE] 10.5% 5.0% 2·11 [1·00, 4·44] 0·04

Cardiac death 0.9% 1.9% 0·50 [0·10, 2·43] 0·4

Targe t ves s el MI 6.5% (21) 1.2% (2) 5·20 [1·23, 21·91] 0·01

Perip ro cedura l MI (WHO) 3.9%(13) 1.2% (2) 3.22 [0.74, 14.11] 0.16

Spontaneo us MI (WHO extended ) 2.5% (8) 0% (0) NC [NC] 0.06

Clinically indicated TLR 3.1% (10) 1.9% (3) 1·65 [0·46, 5·92] 0·56

Patient-oriented compos iteendpoin t [POCE] 20.9% 24.2% 0·86 [0·61, 1·22] 0·4

y 10.8% 17.4% 0 62 [0 39, 0 98] 0.04

Clin ica l endpoin ts

Th e fin d ings of h igh e r non -clin ica lly d r ive n TVR/ TLR ra t e s for Xie nce cou ld h a ve b e e n

a t t r ibu t e d t o t h e u n b lin de d na t u re of t h e in t e rve n t ion . Unb lin de d ph ys icia ns m a y be

p rone t o re a d ily re -in t e rve ne in t h e con t ro l g rou p in pa t ie n t s t re a t e d w it h Xie nce ,

w h e re a s t h e y m igh t h a ve b e e n u n cons ciou s ly re lu ct a n t t o in t e rve ne in t h e

e xpe r im e n t a l d e vice a rm (Abs orb ) , a lt h ou gh t h is a s s u m pt ion is pu re ly s p e cu la t ive a nd

h a s not be e n ob je ct ive ly docu m e n t e d .

2 : 1 randomiza tion

ABSORB China

Primary Endpoin t:In-Segment Late Loss at 1 Year (PTE)

PTE=459 subjects; 86.3% had the angiogram for the Primary Endpoint Analysis

2-Year Clin ica l Compos ite Endpoin ts

oCE=device oriented composite endpoin

Abs orb BVS

(N=241)

XIENCE V

(N=239)P-Va lue

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

Scaffo ld /S ten t Thrombos is

Abs orb BVS

(N=241)

XIENCE V

(N=239)P-Value

All (0 - 730 days) 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 (31- 365 days) 0.0% (0/238) 0.0% (0/232) 1.00

Very Late (366- 730 days) 0.4% (1/237) 0.0% (0/231) 1.00

There were 1 probable , s ubacute (1-30d) ST and 1 definite , very la te ST in the Abs orb BVS arm .

Abs orb BVS

(N=241)

XIENCE V

(N=239)P-Va lue

All (0 - 730 days) 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 (31- 365 days) 0.0% (0/238) 0.0% (0/232) 1.00

Very Late (366- 730 days) 0.4% (1/237) 0.0% (0/231) 1.00

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

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

Thank You!

Documents

0730 Clinical Trials Scripps 2016 - Promedica International · Key Clinical Trials In Interventional Cardiology: 2016 • Left Main Disease (PCI vs CABG): EXCEL, NOBLE • Structural