Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
“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