Post on 28-Jul-2020
Nick Curzen
Predicting & avoiding stent thrombosis at the time of stent implantation
MY POTENTIAL CONFLICTS OF INTEREST ARE:
Consultancy/Speaker Fees: Medtronic; Abbott Vascular; Cordis; Boston Scientific;AstraZeneca; Haemonetics; Sorin; St Jude Medical;Lilly; Solvay
Unrestricted research grants: Medtronic; Haemonetics; Pfizer; St Jude Medical; Medicell; Verathon
Travel Sponsorship: Lilly; Medtronic; Cordis; Boston Scientific; Abbott Vascular;
16-Dec-16
“We do know of certain knowledge that Osama bin Laden is either in Afghanistan ,
or in some other country, or dead.”
16-Dec-16
“As we know, there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some
things we do not know. But there are also unknown unknowns -- the ones we don't
know we don't know."
16 December 2016
The Known Knowns
12/16/2016
Procedure and Stent/Deployment Factors
16-Dec-16
Heart 2004
Fujii K
Carlier S
Mintz G
et al
16-Dec-16
16-Dec-16
12/16/2016
Inadequate Anti-platelet therapy
Late & Very Late Stent Thrombosis
Time Post Procedure & Antiplatelet Therapy at Stent Thrombosis
0 6 12 18 24
Months Post Stent Implant
No Antiplatelets Aspirin Aspirin + Clopidogrel
12/16/2016
Inadequate Response to Anti-platelet therapy
16 December
2016
Individual Response
Standard Dose Aspirin
Standard Dose Clopidogrel
PCI Patient
Enzyme Rise/MI
Stent Thrombosis
16 December
2016
0
10
20
30
40
50
60
70
80
90
100
pre 2hr 6hr 24hr
%C
In
“Percentage clotting inhibition” due to clopidogrel in 10 patients loaded with 600mg clopidogrel prior to elective PCI.
Platelets 2007;18:497-505.
The answer is “YES”, so when are we going to face it??
Tailoring Therapy
16 December 2016
The Known Unknowns
16-Dec-16
Very Late Stent Thrombosis
16/12/2016 20:1349
D
n
n
BMS 24 months after deployment Cypher 16 months after deployment
Circulation 2003;107:1340-1341
Endothelial Dysfunction
16/12/2016 20:1350
Perc
enta
ge E
nd
oth
elializati
on (
%) 100
80
60
40
20
0
Duration Post-Implant (months)
0 2 4 6 8 10 12 14 16 18 20 >40
BMS (n=25)
DES (n=23)
Delayed Endothelialization in DES compared with BMS
JACC 2006:48:000-000
16-Dec-16
Endothelial Dysfunction
D
n
16-Dec-16
Can we avoid ST in some by understanding DAPT better?
Nalyaka Sambu, Alison Calver , Huon Gray, Iain Simpson, Simon Corbett, Nick Curzen
Demographics
27 patients enrolled so far
Mean age 63.1 years
24 (89%) males
5 (19%) diabetics
Time from PCI to ST ranged from 0.02 to
3379 days (mean 1262 days)*
*n=25
At presentation
2 (7%) were on no APT due to non compliance
8 (30%) were on both aspirin and clopidogrel
1 (4%) was on clopidogrel alone
16 (59%) were on aspirin alone
0
10
20
30
40
50
60
70
80
90
100
Adequate response
to both aspirin and
clopidogrel
Inadequate
response to
clopidogrel alone
Inadequate
response to aspirin
alone
Inadequate
response to both
aspirin and
clopidogrel
n=1141%
n=726%
n=14%
n=830%
% N
o o
f p
ati
en
ts
Short TEG results
Response to treatment modification
-20
0
20
40
60
80
100
PRE POST
On Aspirin
On Clopidogrel
Aspirin dose increased
Clopidogrel changed to prasugrel
% c
lott
ing
inh
ibit
ion
16 December
2016
N=1568 N=1569
JAMA 2008;299:532-39
• 33 patients recruited 11 months following PCI with DES
• 82% male; mean age 65.9
• Study timepoints:
4 weeks pre clopidogrel cessation
24 hrs pre clopidogrel cessation
24 hrs, 48 hrs, 1, 2 and 4 weeks post clopidogrel cessation
Effects of Cessation of Clopidogrel Therapy on Platelet Reactivity in Patients with Drug-eluting Coronary Stents:
Is There a “Rebound Phenomenon"?
N Sambu1, T Warner2, A Calver1, S Corbett1, H Gray1, I Simpson1, N Curzen1
1 Wessex Cardiothoracic Centre, Southampton2 William Harvey Research Institute, London
AUC15 ADP Channel (mean, 95% CI)
******
*** *** ***
*** p<0.001
AUC15 AA Channel (mean, 95% CI)
**
**
***
*** **
****
***
*****
** p<0.01 *** p<0.001
TxB2 levels remain negligible throughout indicating that aspirin is consistently blocking COX
Heart 2010
16-Dec-16
Are some people hypersensitive to some devices?
... Curzen’s “POLYMER ENIGMA SYNDROME” !!!!
Virmani R et al. Circulation 2004;109:701-705.
Stent Thrombosis (ARC Def or Prob)
Months
Ste
nt th
rom
bosis
(%
)
Number at risk
XIENCE V 2458 2426 2412 2386 2367 2354 2342 2334 2321
TAXUS1229 1196 1186 1175 1166 1160 1156 1152 1139
1.23%
0.42%
p=0.008
HR [95%CI] =
0.36 [0.17, 0.79]
Δ 0.81%
1.06%
0.29%
p=0.003
HR [95%CI] =
0.27 [0.11, 0.67]
Δ 0.77%
XIENCE V (n=2458)
TAXUS (n=1229)
SPIRIT II, III, IV and COMPARE trials
Pooled database analysis (n=6,789)
Stent thrombosis (ARC)
4247 4183 4141 3467
2542 2474 2446 2113
Number at risk
XIENCE
TAXUS
p<0.001
HR: 0.30 [0.17, 0.52]
0.5%
1.5%
AR
C D
efinite/P
roba
ble
(%
)
0.0
0.5
1.0
1.5
2.0
Time in Months
0 1 2 3 4 5 6 7 8 9 10 11 12
4247 4184 4142 3469
2542 2477 2449 2118
Number at risk
XIENCE
TAXUS
p<0.001
HR: 0.31 [0.17, 0.58]
0.4%
1.2%
AR
C D
efinite (
%)
0.0
0.5
1.0
1.5
2.0
Time in Months
0 1 2 3 4 5 6 7 8 9 10 11 12
EES (n=4,247)
PES (n=2,542)
EES (n=4,247)
PES (n=2,542)
LESSON I: Definite Stent Thrombosis @ 3 Yrs
No. at risk
EES
SES
1342
1342
1296
1271
1234
1216
620
619
543
527
226
223
29
28
3
2
1
0
0 6 12 18 24 30 36
Raber L. ESC 2010
1.6%
0.5%
HR [95%CI] =
0.30 [0.12-0.75]
P=0.01
Months after index PCI
SES (n=1,342)
EES (n=1,342)
De
fin
ite
ste
nt th
rom
bo
sis
(%
)
16-Dec-16
Annals of Biomedical Engineering 2010
16 December 2016
The Unknown Unknowns
16-Dec-16
"I would not say that the future is necessarily less predictable than the past. I think the past was not
predictable when it started."
CONCLUSIONS
Expand your stents properlyUse as little metal as possible.... But...Don’t leave edge dissections
Encourage compliance to antiplatelets
Stop iterating stents.... It won’t make enough differenceto ST rates!!
Check responses of individuals to antiplatelets and tailor therapy accordingly?
16-Dec-16