0730 clinical trials scripps 2016 - promedica international · key clinical trials in...
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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 - -
Death, stroke or MIat 3 years
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)
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 - -
Death, stroke or MIat 3 years
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.
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 - -
Death, stroke or MIat 3 years
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.
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 - -
Death, stroke or MIat 3 years
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.
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 - -
Death, stroke or MIat 3 years
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.
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
603 584 575 409 180 0Deferred612 594 575 403 173 0Conventional
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
603 576 563 395 172 0Deferred612 580 560 391 167 0Conventional
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
603 564 550 383 167 0Deferred612 586 554 379 165 0Conventional
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
603 559 549 382 167 0Deferred612 587 561 387 170 0Conventional
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!
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