Transcript Document

“Edge Technologies: CID Drug Release & Stent Surface
developments”
“Current DAT duration following DES
implantation and CID polymer-free DES
technology”
Federico Piscione, MD, PhD
Federico II University, Naples
Italy
Disclosure Statement of Financial Interest
I, Federico Piscione, DO NOT have a
financial interest/arrangement or affiliation
with one or more organizations that could be
perceived as a real or apparent conflict of
interest in the context of the subject of this
presentation.
DES efficacy
Reduced neo-intima growth → lower late loss (LL) as well
as target lesion revascularization (TLR) rates vs. BMS
Angio efficacy = LL
Clinical efficacy = TLR
DES safety
First available clinical data on DES Death, MI & MACE
rates (1-2 years) were satisfactory
SIRIUS @ 1 Yr
Sirolimus
(533)
Control
(525)
p
Death
1.3 (7)
0.8 (4)
0.547
MI (all)
3.0 (16)
3.4 (18)
0.730
Q-wave
0.8 (4)
0.4 (2)
0.687
Non–Q-wave
2.3 (12)
3.0 (16)
0.449
Events at 360 days
The available clinical results on the first
DES studies led the medical community
to conclude the following:
DES efficacy > BMS efficacy
DES safety = BMS safety
But…
…First concerns on long term DES
safety started to come…
ESC06: DES safety data
ESC06: DES safety data (II)
ROTTERDAM & BERN experience
Overall thrombosis rate in 8146 patients enrolled in Bern (SIRTAX and POSTSIRTAX studies) and Rotterdam (RESEARCH and T-SEARCH) treated with
either Cypher (47%) or Taxus (53%) stents*
Documented stent
thrombosis
30 days
1,2%
1 year
1,7%
2 years
2,3%
3 years
2,9% (152/8146)
*: Presentation at ESC06
Stent Thrombosis timing
EARLY
75%
Early
(n=71)
75%
8
(N=71)
LATE
Late
23%
23%
(n=22)
(N=22)
6
VERY
VeryLATE
late 2%
(n=2)
2%
(N=2)
Overall incidence of stent thrombosis
95 of 6058 patients (1.6%)
4
BMS
N
10
2
0
0
30
50
100
300
Wenaweser P et al. Eur Heart J 2005
Days after PCI
10
8
N
4
N
2
0
LATE
Late
Late
Late
20%
20%
20%
23%
(n=11)
(N=11)
(N=11)
(N=22)
66
VERY
LATE
Very lateVery
Very late
late
19%
19%
19%
2%
(n=10)
(N=10) (N=10)
(N=2)
Overall incidence of stent thrombosis
54 of 3376 patients (1.5%)
44
22
00
0 00
30
30
30
50 50
50 100 100
100 300
Days
PCIPCI
Days
after
Daysafter
after
PCI
300
3001000
1000
1000
Wenaweser P et al. ACC/i2, 2006, Poster Session 2902-74
DES
6
N
EARLY
61%
Early
Early
(n=33)
61%
75%
(N=33)
(N=33)
(N=71)
1000
DES benchmark & REAL DAT duration in
clinical studies
Following ESC06, DAT duration in DES clinical studies has been extended
more and more. In some cases it’s been extended beyond 3years (much
longer than the suggested DAT duration in product IFUs)
Latest available DES
> 6 months
1 year
2 years
3 years
Xience V***
94.4%
71.9%
57.3%
52.4%
Taxus***
94.2%
70.8%
60.5%
52.0%
Endeavor **
92.1%
57.6%
65.4%
48.2%
Biomatrix * (Nobori)
>95%
68.1%
23.4%
19.6%
Knowing that DAT extension may mask late stent thrombosis events, this should
be taken into account when a DES has to be selected.
***: Spirit III study results presented at TCT2009 - *: Leader trial results presented at TCT10 - **: Endeavor IV – Presented TCT2009
Bad news assessed after DES implantation
We are treating an ageing patient population…
Hidden comorbidities may show themselves with dual
antiplatelet therapy!
Patient non-compliant to DAT*
Among 2360 unselected patients undergoing successful DES implantation, 837 reported
bleeding events (32,4% of the overall population). The type of bleeding has been
assessed during the routine clinical follow-up.
100%
Attributable
Clopidogrel
Absolute Clopidogrel
discontinuation (%)
discontinuation (%)
60
100
50 90%
80
80%
40 70%
60
30 60%
4050%
20 40%
2030%
10
20%
0010%
0%
Type of reported bleeding
52.2%
85,7%
43.7%
58.7%
11.2%
13,6%
3.9%
0,7%
Nuisance
bleeding
Internal
bleeding
Alarming
bleeding
Knowing the high risk of stent thrombosis consequent to a premature DAT termination, the
impact of “Nuisance bleeding” on attributable Clopidogrel discontinuation resulted much
higher than expected.
*: The American Journal of Cardiology, Volume 102, Issue 12, Pages 1614-1617 (15 December 2008)
Patients non-responders to Clopidogrel:
The Re-Close study results*
Definite/Probable stent thrombosis
for Responders & Non-Responders to Clopidogrel
Long-term event-free survival for primary
endpoint
Primary endpoint: definite/probable DES
thrombosis during the first 6 months
follow-up
*:
Re-Close study results presented by Dr Antoniucci during TCT08
What about new anti-platelet compounds?
Is stronger/ longer/ infinite DAT regimen the solution? Trials data on new drugs
have been recently disclosed, but the benefits (less ST, MI, CVA…) remain
mainly focused on short term vs. the potential long-term risks (bleeding)
Which is the economic impact of DAT
duration extension?
Expenses for DAT therapy with current & newer DES
Assumptions:
• 2M pts per year receive DES
5
4,5
• “ON-label” use (=6 months DAT) = 30%*
42% = 12 months
28% > 12 months
• Cost of Clopidogrel = 100 US$/month
Billion US$ -
• “OFF-label” use (≥12 months DAT) = 70%*
4
3,5
3
Newer DES
2,5
2
1,5
1
Current DES
0,5
0
First year
Second year
Third year
Forth year
Fifth year
In this simulated case, DAT treatment with a current DES is compared to a foreseen
DES which can allow for a DAT treatment of max 6-month (the number of procedures
and the cost of Clopidogrel remain the same for 5 years)
*: data presented at EuroPCR07 (70% Off-label DES use, 40% of which requires the longest possible DAT duration)
CID DES – Optima
Polymer-free
CID Carbostent™
Technology
Polymer coated DES
vs
Stent
+ Drug
Stent
+ Polymer
+ Drug
 Lack of inflammatory polymers
 No thrombogenic surface towards the bloodstream and
the vessel wall
NO polymer drawbacks
CID DES - Optima Jet
Abluminal Reservoir Technology

Drug release only towards the vessel wall

100% drug release

Deep reservoir maintains the drug concentration gradient vs. vessel wall
drug release maintained for 2-3 months
The clinically proven* bio & haemo-compatible CarbofilmTM coating* is the
only contact surface with the blood and the vessel wall.

*Data on CarbofilmTM thromboresistance available in published clinical studies (SAFE, ANTARES, HURRICANE, SIMPLE)
DES endothelialization in
complex settings: Animal studies results
Two DES in overlapping implantation
(results at 28days)*
Carbostent
DES
Endothelialization of Carbostent
DES located over the ostium of a
side branch**
Other DES
*: study performed by Virmani. Presented at EuroPCR05 & EuroPCR06
**: Presented during TCT07 (Courtesy of dr. Perez De Prado, Leon – Spain)
Randomized clinical trial:
8-months results* - 60%
- 54%
16
15
p = 0.038
13
14
12
p = 0.059
% 10
8
6
6
6
4
Carbostent DES
BMS
2
0
1
0
1
0
Cardiac death
MI
TLR
MACE
Dual antiplatelet therapy duration Carbostent DES
BMS
4 months
100%
100%
Carbostent DES
BMS
Acute
0%
0%
Sub-acute
0%
0%
Late
0%
0%
Stent thrombosis
*: Han et al. Chin Med J 2007; 120 (7): 552-556
Matrix Registries I* & II**
MATRIX I REGISTRY - 553 patients
Evaluation of safety and efficacy of Tacrolimus Eluting Carbostent in real world
patients who underwent PCI, with two period of dual anti-platelet therapy (DAT)
2 months DAT
Vs
6 months DAT
MATRIX II REGISTRY – 392 patients
Evaluation of safety and efficacy of OPTIMA Tacrolimus-Eluting Carbostent in
real world patients undergoing PCI, followed by only two months of dual
anti-platelet therapy (DAT)
2 months DAT
*: S.Cassese et al – Catheterization and Cardiovascular Intervention, IN PRESS **: Presented during GISE2010 – Dr S.Cassese
Matrix I Registry - 12 m results*
2 months
pts
6 months
pts
30 days
97,86% (94,41 – 99,19)
181
98,37% (96,41 – 99,27)
358
352
6 months
97,86% (94,41 – 99,19)
172
97,25% (94,96 – 98,52)
348
325
12 months
96,95% (94,57 – 98,30)
322
2 months
pts
6 months
pts
30 days
99,46% (96,25 – 99,92)
184
99,44% (97,81 – 99,86)
359
6 months
99,46% (96,25 - 99.92)
175
99,16% (97,44 – 99,73)
12 months
99,46% (96,25 – 99,92)
170
98,86% (97,00 – 99,57)
Months
Acute Thrombosis
Sub - Acute Thrombosis
Late Thrombosis
(up to 6 months)
Late Thrombosis
(up to 12 months)
1
2
3
4
5
6
7
8
9
10
11
12
190 Pts
2 months DAT
0
0
0
0
382 Pts
97,29% (93,63 – 98,87)
164
6 months DAT
1
0
Total %
0,17%
0%
0
0%
0
0%
*: S.Cassese et al – Catheterization and Cardiovascular Intervention, IN PRESS
Matrix II Registry
Primary Endpoint
- Incidence of Major Adverse Cardiac Events (MACE) within 12 and 24 months after
implant procedure.
Secondary Endpoint
- Thrombosis rate within 30 days, 6, 12 and 24 months after implant procedure
Patients
392 pts
Diabetes
25.0%
Unstable angina
25.0%
NSTEMI + STEMI>48h
30.4%
Multivessel disease
57.4%
Number of lesions
Bifurcations
440
24.8% (109)
Ostial lesions
4.3% (19)
CTOs
5.4% (24)
Intracoronary thrombus
13.4% (59)
Lesion length (mm)
Lesion classification ACC/AHA
Presented during GISE2010 – Dr Cassese
16.4±6.6
Vessel distribution
Matrix II Registry – Results (I)
Results at 12 months - Primary Endpoint
95,11 %
93,80 %
Cumulative incidence of TLR 4,89 %
2 months DAT
pts
30 days
98.96% (97.28 - 99.61)
387 pts
6 months
95.70% (93.09 - 97.35)
12 months
93.80% (90.07 - 95.52)
2 months DAT
pts
30 days
99.74% (98.17 - 99.96)
387 pts
367 pts
6 months
96.46% (93.99 - 97.93)
367 pts
291 pts
12 months
95.11% (92.25 – 96.95)
291 pts
Presented during GISE2010 – Dr Cassese
Matrix II Registry – Results (II)
Results at 12 months – Secondary Endpoint
Months
Acute Thrombosis
Sub - Acute
Thrombosis
Late Thrombosis
(up to 6 months)
Late Thrombosis
(up to 12 months)
392 Pts
2 months DAT
1
1
Total %
0,2%
0%
0
2
3
4
5
6
7
8
9
10
11
12
0
0
0%
0%
Presented during GISE2010 – Dr Cassese
99,1 %
ESC Guide lines for PCI in AF patients
…..”The use of DES of first and second generation, due to the
prolonged need of dual antiplatelet therapy, should be avoided in
patients with an indication for long-term OAC”….
AF patients who would benefit from DES efficacy?
...”the new third generation DES seem to have accelerated reendothelialisation and might become of interest. Retrospective registries
(e.g.Italian Matrix registry) and trail to test their usefulness are currently
performed”…
Thromb Haemost. 2010 Jan;103(1):13-28
CONCLUSIONS
 Following ESC06, DAT duration in real-world PCI with DES has been
extended much beyond 1 year heavily impacting on countries’ health budget.
 Clopidogrel hypo-responsiveness, DAT compliance or bleeding may expose
patient to higher risk of DES thrombosis with a consequent increased risk of
cardiac death or MI.
 The OPTIMA DES (polymer-free, abluminal reservoir, integral CarbofilmTM,
Tacrolimus drug elution and the new delivery system) has been specifically
developed to optimize DES efficacy and safety.
 All the clinical data collected up to today confirm excellent CID DES
technology safety & very positive outcomes in “real world” population,
including high risk patients. These results have been achieved with short dual
antiplatelet therapy duration.
 OPTIMA is the only DES to allow 2 months DAT - Specific patients’
populations such as AF and high risk of bleeding today can benefit from the
DES efficacy thanks to CID DES