high tech - marseille 25 au 27 janvier 2011 marie-claude morice, md, fesc, facc massy, france
DESCRIPTION
Moins de 6 mois d’antiagrégants après DES ?. High Tech - Marseille 25 au 27 janvier 2011 Marie-Claude MORICE, MD, FESC, FACC Massy, France Pas de conflit d’interet. Was optimal duration of DAPT already established for BMS?. Stable&unstable angina. 2,116 pts. 1 year vs. 30 days of DAPT. - PowerPoint PPT PresentationTRANSCRIPT
High Tech - Marseille25 au 27 janvier 2011Marie-Claude MORICE, MD, FESC, FACC Massy, France
Pas de conflit d’interet
Moins de 6 mois d’antiagrégants après DES ?
Was optimal duration of DAPT already established for BMS?
Stable&unstable angina
2,116 ptsmedian DAPT duration8 months
Acute coronary syndromes
1 year vs. 30 days of DAPT
No difference in bleeding Slight increase in bleeding (P=0.07)
:
Are DES particularly vulnerable to thrombosis?
100
90
80
70
60
50
40
30
20
10
0 1 2 3 4 5 6 7 8 9 11 15 16 17 20 >40
Duration (months)
En
doth
elis
atio
n (%
)
BMS
DES
From autopsies of 23 patients treated with DES >30 days and 25 matched BMS-treated autopsies
Joner et al, JACC 2006
Are DES particularly vulnerable ?
PES
SESBMS
Stettler et al. Lancet 2007
Everolimus-eluting stents vs. non-everolimus-eluting stents
Baber et al. JACC in press
1 Year ST Rate (ARC Def/Prob)Overall Population
0.44%0.2%
2%
0.39%0.4%
0.9%
0.0%
0.5%
1.0%
1.5%
2.0%
2.5%
3.0%
ST
(A
RC
Def
/Pro
b) (
%)
Early (< 30 Days) Late (30 Days - 1 Year)
6
1 Kedhi E. et al Lancet. 2010; 375 (9710): 174-6.
COMPARE1
XIENCE V USA
XIENCE V
TAXUSXIENCE V
0.84%0.7%
3%
p = 0.002
BioMatrix FlexTM
• Biolimus is a semi-synthetic sirolimus analogue with 10x higher lipophilicity and similar potency as sirolimus.
• Biolimus is immersed at a concentration of 15.6 g/mm into a biodegradable polymer, polylactic acid, and applied solely to the abluminal stent surface by a fully automated process.
• Biolimus is co-released with polylactic acid and completely desolves into carbon dioxide and water after a 6-9 months period.
• The stainless steel stent platform has a strut thickness of 120 m with a quadrature link design.
O
O
O OH
OO
OO
OO
N
OH
O
O
O
NOBORI – DAT StudyNobori DES components
BMS Platform PLA Biodegradable Polymer Biolimus A9™ (rapamycin derivative)
Excellent Flexibility and Scaffolding
Optimal Side Branch Access
Innovative Delivery System with Hydrophilic M-coating
Abluminal Coating
Controlled Biodegradability
Precise Drug Release Kinetics
Simultaneous Polymer Degradation and Drug Release
A Potent New “Limus” Designed for Stent Applications
Powerful Anti-proliferative and Anti-inflammatory properties
Highly Lipophilic with Optimal Local Tissue Uptake
LEADERS: Definite ST in Complex PatientsSTEMI
1.0
2.0
3.0
%
2.6%
5.1%
0 6 12 18 24 3630Months
2.6%
5.1%4.6%
2.6%
3-year HR0.50 [0.18 to 1.34]
P = 0.16*
0
4.0Δ2.0% Δ3.5% Δ3.5%
5.0
6.0
High SYNTAX SCORE (>16)
1.0
2.0
3.0
%
2.0%
4.3%
0 6 12 18 24 3630Months
2.0%
3.8%
2.5%
2.0%
3-year HR0.46 [0.16 to 1.35]
P = 0.15*
0
4.0
Δ0.5%Δ1.8%
Δ2.3%
5.0
6.0
Bifurcation
1.0
2.0
3.0%
1.5%
5.2%
0 6 12 18 24 3630Months
1.5%
5.2%
3.4%
1.5%
3-year HR0.28 [0.08 to 1.03]
P = 0.04*
0
4.0
Δ1.9%Δ3.7% Δ3.7%
5.0
6.0
Multi Vessel
2.0
4.0
6.0
%
BESSES
0 6 12 18 24 3630Months
3.8%
8.1%8.1%
3.0%
3-year HR0.45 [0.16 to 1.31]P = 0.14*
0
8.0
Δ 5.1%Δ 4.3%
10.0
3.8%
8.1%
Δ 4.3%
*P values for superiorityWindecker, S., oral presentation ,TCT 2010
LEADERS :Effect of DAPT Discontinuation
%%
N=0/165 N=4/169 N=2/515N=0/540
Overall Population Patient who d/c
DAPTP = 0.12*
P = 0.24*
*P values for superiority (Fisher Exact Test)** KM estimates
N=24/850N=19/857
0,0%
0,5%
1,0%
1,5%
2,0%
2,5%
3,0%
0,37% 0,49%
0,26%0%
Late ST Rates (30 Days - 1 Year)After DAPT Interruption
Su
bse
qu
ent
Lat
e S
T (
AR
C D
ef/P
rob
) (%
)
No Interruption Interruption After 30 Days*
13/3500 0/292
Interruption After 180 Days*
2/435
Interruption After 90 Days*
1/378
Overall
11
*Out to 1 year
NOBORI 2- DAT Study
Primary Endpoint: Target Lesion Failure at 12 months
Composite of Death, MI Target vessel related and TLR
Clinical Follow-Up up to 5 years
DAT group:Patients under DAT at 1 year
n=2303
non-DAT group:Patients who stopped DAT earlier
n=668
12 months data for DAT available for 2971 patients
12 Months FU = 97%
DAT
N=2303
Non-DAT
N=668P-value
Age, years (meanSD) 64.2±11.0 64.7±10.6 0.4
Male, % 79.2 74.4 <0.01
Previous MI, % 32.2 36.1 0.07
Prior PCI, % 33.2 28.7 0.03
Prior CABG, % 9.4 7.4 0.1
Diabetes Mellitus, % 31.2 22.8 <0.01
Insulin-dependent, % 7.3 5.6 0.1
Hyperlipidemia, % 71.0 73.9 0.2
Hypertension, % 68.2 71.8 0.08
Current smoker, % 25.4 26.0 0.8
Charlson Comorbidity, N (meanSD)
3.16±1.79 3.18±1.66 0.6
NOBORI – DAT StudyBaseline Demographics
Temporary Interruption % (N) 5.6% (N = 243)
Number of Interruptions 1.1 ± 0.5 (N = 243)
Days to First Interruption (days) 134.3 ± 121.4 (N = 243)
Duration of Interruption (days) 20.3 ± 46.9 (N = 243)
Top 3 Reasons for Interruption Surgical Procedure = 35.4%Adverse Event** = 30.5%Patient Non-compliance = 9.5%
Permanent Discontinuation % (N) 8.5% (N = 366)
Days to Discontinuation (days) 239.2 ± 140.4 (N = 366)
Top 3 Reasons for Discontinuation Adverse Event** = 21.9%Surgical Procedure = 10.7%Increased Bleeding Risk = 9.6%
DAPT Interruption Pattern*
14
*Out to 1 year**Adverse Events include all events regardless of their severity and/or relationship with drugs or device
DATN=2303
Non-DATN=668
P-value
Cardiac Death % 0.6 0.2 NS
MI % 1.7 0.6 0.04
TLR - CABG % 0.4 0.5 NS
TLR - PCI % 2.0 0.5 0.003
TVR, non TL % 1.2 0.6 NS
TLF % 3.6 1.4 0.002
MACE % 4.7 2.1 0.003
Stent Thrombosis % – Early 0.4 0.0 NS
Stent Thrombosis % – Late 0.1 0.0 NS
Stent Thrombosis % – Total 0.5 0.0 NS
TLF = Target Lesion Failure (Cardiac death, MI, clinically driven TLR);
ST = Definite/Probable according to ARC; MACE = Cardiac Death, any MI, TVR
NOBORI – DAT StudyClinical outcomes at 1 year
0,2 0,2
0,5
0,1 0,2
1,2
0,9
0,00,0
0,5
0,9
0,40,4
0,0
0,5
0,00,0
1,0
2,0
CardiacDeath
MI TVR-CABG
TLR-PCI TVR-NTL MACE TLF ST
(%)
Events during DAT
Events after stopping DAT
TLF = Target Lesion Failure (Cardiac death, MI, clinically driven TLR);
ST = Definite/Probable according to ARC; MACE = Cardiac Death, any MI, TVR
NOBORI – DAT StudyPatients that stopped DAT before 1 year
Conclusions• In 3 large trials, real-world population of
respectively 3000, 1400, 5000 patients, NOBORI, BIOSENSOR and XIENCE V stents demonstrates very low stent thrombosis rates for the whole population
• In a real-world experience of unanticipated DAPT interruption, the 3 stents had an observed near zero ST event rate afterDAPT interruption.17
Conclusions
• Shorter dual antiplatelet treatment is vital for some patients,
• If confirmed by prospective comparative studies ( 3 or 6 months compared to 1 year), these new generation of stent will fullfill our expectations
18
•And even less than 3 months?
.- the ZEUS trial (PI Marco Valgimigli) who is randomizing patients at risk of bleeding to Endeavor or BMS with a minimum length of DAPT of 1 month. - The Leaders free trial
BioFreedom™Selectively micro-structured surface holds drug in
abluminal surface structures
Proprietary Highly Lipophilic Limus drug
Hypothesis: Polymer-free drug release via porous-eluting stents
may reduce late events caused by polymer stent coatings.
Potential advantage
• Avoid long term late adverse effects that might be attributable to the polymer
• Improved surface integrity since there is no polymer to be sheared or peeled away from the stent struts
• Possible shorter need of dual antiplatelet therapy
Tada et al., Circ Cardiovasc Interv 2010;3;174-183
Pre-Clinical Safety Evaluation
2nd Cohort PRIMARY ENDPOINTP = 0.001* (p=0.11**)
P = 0.21* (p=0.55**)
(m
m)
N = 31 N = 31N = 35
*Non-inferiority tests. **Superiority tests.Grube E., oral presentation, TCT 2010
In-Stent LLL at 12 Months FU
A PROSPECTIVE RANDOMIZED COMPARISON OF THE BIOFREEDOMTM BIOLIMUS A9TM DRUG COATED STENT VERSUS THE GAZELLE™ BARE METAL STENT IN PATIENTS AT HIGH RISK FOR BLEEDING
LEADERS FREE PROTOCOL
Title: LEADERS FREE
Devices Used: - Biosensors BioFreedom™ BA9 Drug Coated Coronary Stent- Biosensors Gazelle™ Bare Metal Coronary Stent
Antiplatelet Therapy: ASA once a day for one month (indefinitely at the discretion of the investigator) AND Clopidogrel or P2Y12 inhibitor (choice of the investigator) for one month
LEADERS FREE:PROTOCOL
Design: multi center, multi-national out of US double blinded, randomized, trial designed to enroll 2500 patients at up to sixty centers worldwide. Patients will be randomized at 1:1 ratio to the stent treatment. All patients will be followed for two years.
Organisation:
PI: P Urban, I Meredith, A Abizaid Sponsor/ BIOSENSORS CRO: CERC
PROTOCOL
Objectives: Safety: 1) To demonstrate in symptomatic CAD patients who are unsuitable for >1 month treatment with dual antiplatelet therapy (DAPT) that the Biosensors BioFreedom™ Drug Coated Stent (DCS) followed by one month DAPT is non-inferior to the Gazelle™ Bare Metal Stent
(BMS) followed by one month DAPT as measured by the composite primary endpoint of cardiac death, myocardial infarction, stent thrombosis and urgent target lesion revascularization (TLR) at one year.
Efficacy: 2) To demonstrate in symptomatic CAD patients who are unsuitable for >1 month treatment with DAPT that the Biosensors BioFreedom™ DCS followed by one month DAPT then followed by aspirin only indefinitely is superior to the Gazelle™ BMS followed by one month DAPT as measured by the incidence of clinically driven TLR at one year.
LEADERS FREE/ INCLUSION CRITERIA
Any indication for PCI-S in patients Deemed at high risk for bleeding and candidates for 1 month DAPT
1- Adjunctive oral anticoagulation treatment planned to continue after PCI
2- Age ≥ 75 years old
3- Baseline Hgb <11 g/dl (or anemia requiring transfusion during the 4 weeks prior to randomization)
4- Any prior intracerebral bleed
5- Any past <=1 year stroke
6- Hospital admission for bleeding during the prior 12 months
7- Cancer diagnosed or treated <= 3 years
8- Planned daily NSAID (other than aspirin) or steroids for >=30 days after PCI
9- Planned major surgery (within 1 year)
10- Expected non-compliance to prolonged DAPT for other reasons
Alors, les BMS…… au musée?
Thank you for your attentionThank you for your attention