Moins de 6 mois d antiagrégants après DES?

Transcription

1 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

2 Was optimal duration of DAPT already established for BMS? 1 year vs. 30 days of DAPT Acute coronary syndromes Stable&unstable angina median DAPT duration 8 months 2,116 pts No difference in bleeding Slight increase in bleeding (P=0.07) :

3 Are DES particularly vulnerable to thrombosis? From autopsies of 23 patients treated with DES >30 days and 25 matched BMS-treated autopsies Endothelisation (%) BMS DES >40 Duration (months) Joner et al, JACC 2006

4 Are DES particularly vulnerable? PES SES BMS Stettler et al. Lancet 2007

5 Everolimus-eluting stents vs. non-everolimus-eluting stents Baber et al. JACC in press

6 1 Year ST Rate (ARC Def/Prob) Overall Population 3% p = % 0.7% XIENCE V XIENCE V USA 1 Kedhi E. et al Lancet. 2010; 375 (9710): XIENCE V COMPARE 1 TAXUS 6

7 BioMatrix Flex TM 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 µg/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 µm with a quadrature link design.

8 NOBORI DAT Study Nobori DES components BMS Platform PLA Biodegradable Polymer Biolimus A9 (rapamycin derivative) Excellent Flexibility and Scaffolding Abluminal Coating Controlled Biodegradability A Potent New Limus Designed for Stent Applications Optimal Side Branch Access Innovative Delivery System with Hydrophilic M-coating Precise Drug Release Kinetics Simultaneous Polymer Degradation and Drug Release Powerful Anti-proliferative and Anti-inflammatory properties Highly Lipophilic with Optimal Local Tissue Uptake

9 % LEADERS: Definite ST in Complex Patients BES SES 8.1% Δ 5.1% 3.0% STEMI 8.1% Δ 4.3% 3.8% 3-year HR 0.45 [0.16 to 1.31] P = 0.14* 8.1% Δ 4.3% 3.8% % High SYNTAX SCORE (>16) 4.6% 2.6% 2.6% 5.1% 3-year HR 0.50 [0.18 to 1.34] P = 0.16* 5.1% Δ2.0% Δ3.5% Δ3.5% 2.6% Months Bifurcation 3-year HR 0.46 [0.16 to 1.35] P = 0.15* Months Multi Vessel 3-year HR 0.28 [0.08 to 1.03] P = 0.04* % % 5.2% % % Δ0.5% 2.0% 3.8% Δ1.8% 2.0% Δ2.3% 2.0% % % Δ1.9% 1.5% Δ3.7% 1.5% Δ3.7% 1.5% Months *P values for superiority Windecker, S., oral presentation,tct Months

10 Overall Population LEADERS :Effect of DAPT Discontinuation P = 0.12* Patient who d/c DAPT P = 0.24* N=19/857 N=24/850 N=0/165 N=4/169 N=0/540 N=2/515 *P values for superiority (Fisher Exact Test) ** KM estimates

11 Subsequent Late ST (ARC Def/Prob) (%) *Out to 1 year Late ST Rates (30 Days - 1 Year) No Interruption After DAPT Interruption 13/3500 2/435 1/378 0/292 Interruption After 30 Days* Interruption After 90 Days* Overall Interruption After 180 Days* 11

12 12 months data for DAT available for 2971 patients NOBORI 2- DAT Study DAT group: Patients under DAT at 1 year n=2303 Clinical Follow-Up up to 5 years non-dat group: Patients who stopped DAT earlier n=668 Primary Endpoint: Target Lesion Failure at 12 months Composite of Death, MI Target vessel related and TLR 12 Months FU = 97%

13 DAT N=2303 Non-DAT N=668 P-value Age, years (mean±sd) 64.2± ± Male, % <0.01 Previous MI, % Prior PCI, % Prior CABG, % Diabetes Mellitus, % <0.01 Insulin-dependent, % Hyperlipidemia, % Hypertension, % Current smoker, % Charlson Comorbidity, N (mean±sd) NOBORI DAT Study Baseline Demographics 3.16± ±

14 DAPT Interruption Pattern* Temporary Interruption % (N) 5.6% (N = 243) Number of Interruptions 1.1 ± 0.5 (N = 243) Days to First Interruption (days) ± (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) ± (N = 366) Top 3 Reasons for Discontinuation Adverse Event** = 21.9% Surgical Procedure = 10.7% Increased Bleeding Risk = 9.6% *Out to 1 year **Adverse Events include all events regardless of their severity and/or relationship with drugs or device 14

15 NOBORI DAT Study Clinical outcomes at 1 year DAT N=2303 Non-DAT N=668 P-value Cardiac Death % NS MI % TLR - CABG % NS TLR - PCI % TVR, non TL % NS TLF % MACE % Stent Thrombosis % Early NS Stent Thrombosis % Late NS Stent Thrombosis % Total NS TLF = Target Lesion Failure (Cardiac death, MI, clinically driven TLR); ST = Definite/Probable according to ARC; MACE = Cardiac Death, any MI, TVR

16 NOBORI DAT Study Patients that stopped DAT before 1 year TLF = Target Lesion Failure (Cardiac death, MI, clinically driven TLR); ST = Definite/Probable according to ARC; MACE = Cardiac Death, any MI, TVR

17 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

18 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

19 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

20 Selectively micro-structured surface holds drug in abluminal surface structures BioFreedom Hypothesis: Polymer-free drug release via porous-eluting stents may reduce late events caused by polymer stent coatings. Potential advantage Proprietary Highly Lipophilic Limus drug 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

21 Pre-Clinical Safety Evaluation Tada et al., Circ Cardiovasc Interv 2010;3;

22 2 nd Cohort PRIMARY ENDPOINT In-Stent LLL P = 0.001* at (p=0.11**) 12 Months FU P = 0.21* (p=0.55**) (mm) N = 31 N = 35 N = 31 *Non-inferiority tests. **Superiority tests. Grube E., oral presentation, TCT 2010

23 A PROSPECTIVE RANDOMIZED COMPARISON OF THE BIOFREEDOM TM BIOLIMUS A9 TM DRUG COATED STENT VERSUS THE GAZELLE BARE METAL STENT IN PATIENTS AT HIGH RISK FOR BLEEDING

24 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

25 LEADERS FREE:PROTOCOL Design: Organisation: 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. PI: P Urban, I Meredith, A Abizaid Sponsor/ BIOSENSORS CRO: CERC

26 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.

27 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

28 Alors, les BMS au musée?

29 Thank you for your attention